Podcasts about Carboplatin

Interview with Jennifer A. Pietenpol, PhD, Brian D. Lehmann, PhD, and Vandana G. Abramson, MD, authors of Atezolizumab in Combination With Carboplatin and Survival Outcomes in Patients With Metastatic Triple-Negative Breast Cancer: The TBCRC 043 Phase 2 Randomized Clinical Trial. Hosted by Mary L. (Nora) Disis, MD. Related Content: Atezolizumab in Combination With Carboplatin and Survival Outcomes in Patients With Metastatic Triple-Negative Breast Cancer

Interview with Jennifer A. Pietenpol, PhD, Brian D. Lehmann, PhD, and Vandana G. Abramson, MD, authors of Atezolizumab in Combination With Carboplatin and Survival Outcomes in Patients With Metastatic Triple-Negative Breast Cancer: The TBCRC 043 Phase 2 Randomized Clinical Trial. Hosted by Mary L. (Nora) Disis, MD. Related Content: Atezolizumab in Combination With Carboplatin and Survival Outcomes in Patients With Metastatic Triple-Negative Breast Cancer

In this "Podcast Takeover," Dr. Lidia Schapira guest hosts to discuss with Dr. Shannon Westin her own JCO paper, which reports on the DUO-E Trial. Dr. Ramez Eskander also joins in this lively discussion. TRANSCRIPT The guest on this podcast episode has no disclosures to declare. Dr. Shannon Westin: Hello, everyone, and welcome to another episode of JCO After Hours, the podcast where we get in depth on manuscripts published in the Journal of Clinical Oncology. I am your host, Shannon Westin, Social Media Editor of the JCO and Gynecologic Oncologist by trade. And actually, I'm super excited today because we are going to have a podcast takeover because we are discussing my own work, which was simultaneously presented at the European Society of Medical Oncology 2023 Congress and published in the Journal of Clinical Oncology on October 21st, 2023. And this was the DUO-E trial, “Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer.” Because we're discussing this work and we wanted you to have an unbiased podcast discussion, Dr. Lidia Schapira, who is a Professor of Medical Oncology at Stanford University and an Associate Editor of JCO and the Art of Oncology podcast host, is going to take over this podcast and really just pepper me with questions about this exciting work.  Welcome, Dr. Schapira.  Dr. Lidia Schapira: Thank you so much. It's such a pleasure to be with you. Dr. Shannon Westin: And before I turn over the reins, I also want to introduce one of my colleagues, who's going to be providing quite a bit of insight on this topic, Dr. Ramez Eskander, who is Professor of Obstetrics, Gynecology, and Reproductive Sciences at the University of California, San Diego. And you will know he's the principal investigator of the GY-018 study, which established pembrolizumab and chemotherapy as the new standard of care in endometrial cancer. Welcome, Ramez.  Dr. Ramez Eskander: Thank you. Thank you, Dr. Westin. It's a pleasure to be here. And congratulations again to you and your study team for this exceptional work.  Dr. Shannon Westin: Thank you. And congratulations to you.  Dr. Schapira, thank you for being here and please do take it away. Dr. Lidia Schapira: So let's start by having you tell us a little bit about the standard of care for women with endometrial cancer and advanced endometrial cancer prior to this study. Ramez, I'm going to direct this question to you first. Dr. Ramez Eskander: For many years, actually since about 2012, carboplatin and paclitaxel, which ironically is a chemotherapy backbone really across all of our gynecologic tumors, emerged as the preferred doublet chemotherapy regimen for the management of advanced-stage metastatic or recurrent endometrial cancer. It evolved through a series of different clinical trials, in fact taking us from whole abdominal radiation, systemic chemotherapy, comparing single agents to doublets and then triplet regimen of TAP to carboplatin and paclitaxel, which ultimately, then, following the presentation of GOG Protocol 209 and its publication, as the chemotherapy backbone, being carboplatin and paclitaxel. And it's been that way for many, many years. Dr. Lidia Schapira: And how effective is the regimen? Dr. Ramez Eskander: The response rates to carboplatin and paclitaxel are actually quite reasonable in the patients who have advanced-stage disease, particularly if they haven't had prior systemic chemotherapy. Response rates in the 50% to 60% range. The issue is that the responses tend to be limited and disease recurrence is an expectation in these patients who have advanced-stage disease. And so that really highlighted the importance of trying to continue to advance therapeutic opportunities in these patients to improve long-term outcomes.  Dr. Lidia Schapira: As we think about improved long-term outcomes, we're thinking about a better treatment and also a kinder treatment, perhaps one that is also less toxic. Can you talk a little bit about the population of women with endometrial cancer? Are these older women? Do they have comorbidities?  Dr. Ramez Eskander: What we're seeing is, interestingly, there has been an evolution a bit in this space. Historically, we used to think about endometrial cancer as—the phrases we used to use are type I and type II. These type I tumors, we would say, are estrogen-driven malignancies; they tend to be seen in overweight or obese patients. And we would identify them in a theoretically younger patient population. And then we had these type II, or what we termed estrogen-independent malignancies, that we would see in an older patient population. Of course, with obesity came metabolic syndrome and other cardiovascular comorbidities, etc. But really, that narrative has evolved dramatically, and that's really something that will be highlighted in, I think, our discussion of these studies today, where the nomenclature that we used to historically use has evolved because of our understanding of the molecular characterization of this disease. So we've really gone away from that, and now we understand that we're seeing all of these different heterogeneous endometrial cancer types amongst patients of different ages, different comorbidities, different races and ethnicities. And so it's created a more complex picture for us. But certainly, there are comorbidities that these patients face, and that's important as we look to identify treatments strategies that are both effective and tolerable. Dr. Lidia Schapira: My final question before we jump into this very exciting study is about the Cancer Genome Atlas work. Can you tell us how that's changed the thinking and the design of the studies? Dr. Ramez Eskander: It was a seminal publication, really, back in 2012/2013 looking at an assessment of endometrial cancers to try and determine whether or not all of these "endometrial cancers" that we used to enroll on a single study are similar or divergent. And it's important because the study I referenced that really established the standard of care, GOG Protocol 209, as carboplatin and paclitaxel, there was no real consideration of molecular characterization at all. We enrolled all patients onto this study without thinking about these variables, of course, because it was designed, conducted, and completed before the TCGA data emerged. But what we learned from the TCGA is there appeared to be four distinct molecular subgroups. There were the POLE-mutated patient population. There was the mismatch repair deficient or MSI-high endometrial cancer population. There was the copy number-high or what we say are the p53-mutated. And then the last cohort was called the NSMP (no specific molecular profile). But now, that's even evolved; some people term it TP53 wild type. That's a bit of even a heterogeneous cohort amongst itself. So we're going to take these subsets, independent of POLE and an MSI-high, and we're going to look at TP53 or copy number-high, and that will probably be divvied out further, and the NSMP, and that will probably be subdivided. But really, it gave us these four components, which has then evolved. Many of you may have heard of the ProMisE algorithm or ProMisE Plus, which looked to take the data from TCGA so that we can start to really look at it in clinical practice. So it's really revolutionized how we think about these patients, how we think about the disease, and how we design trials.    Dr. Shannon Westin: And I just want to add to that because I think that it's so important, what Ramez said about the way we were developing trials, the way we were designing trials. We knew that these classifiers—we were learning these classifiers are prognostic. Now what we're really trying to hone in on is how predictive they are. And certainly, one of the major classifiers that we're going to talking about today is mismatch repair status, and that is most definitely predictive of response to therapies. But we're still learning about the other classifiers and how we might adjust the way we treat people, even deescalating care for certain patients. That is still being proven in clinical trials, although we suspect that it's going to be borne out as other clinical trials report. Dr. Lidia Schapira: It's a perfect segue to this current trial. Tell us a little bit about the objectives and the design of DUO-E. Dr. Shannon Westin: As Ramez said, the standard of care was chemotherapy. And so we wanted to see if there was a way to improve outcomes for these women with advanced and recurrent endometrial cancer in a really clinically relevant, meaningful fashion for patients. And so we knew that this TCGA classifier, the mismatch repair, was so important, and we thought that the addition of immunotherapy to chemotherapy would most certainly work in that population but could even work in the entire population because, generally, endometrial cancer seems to be a little bit more responsive to immunotherapy and to activation of the immune system than, say, some of our other gynecologic malignancies. And so we set out to see what the addition of durvalumab, which is a PDL-1 inhibitor, would add to chemotherapy. And this was two chemo as well as followed by durvalumab maintenance.  But even further, we had some really kind of exciting science data from our lab that said that if we combined a PARP inhibitor with immunotherapy that we could accentuate on the response to therapy and we could get more benefit. And there's kind of a lot behind that, but essentially, what we thought was that the damage that's caused by the PARP inhibitors would create an activation of different immuno-pathways, like STING pathway and activating cytokine release, and that we would get this synergistic activity. So one of the other objectives was to see if the addition of the olaparib, the PARP inhibitor, to durvalumab in that maintenance setting could even further improve benefit. So we had a dual primary endpoint looking at progression-free survival, so the amount of time people live without their cancer coming back. And that endpoint was first, the durvalumab-alone arm to control, and then the second portion of that was the durvalumab/olaparib arm back to control. Dr. Lidia Schapira: So before you tell us about the results, tell us a little bit about the study itself. I mean, I was very impressed that you did it in so many different locations. Tell us about that effort.  Dr. Shannon Westin: This was a huge collaborative effort both with the GOG Foundation, the Gynecologic Oncology Group Foundation, as well as ENGOT, which is our European colleagues that do amazing clinical trials. But in addition to that, we really worked very closely with our industry partner to really make sure we spanned the globe. And so we had groups from all over the world that participated and really were exceptional. The care that was taken and the hard work that went into this type of study across the world really can't be overstated. We were very lucky to have a wonderful infrastructure group. We met weekly for a long time, just keeping an eye on the data and making sure that everything was as positive as possible and, of course, that we were watching the outcomes of the patients very closely and making sure that there was no evidence of harm or issue. And so it really did take a village, truly, to run this study and to ensure that at the end of it, we got really great data that we can trust. Dr. Lidia Schapira: So tell us the results. Dr. Shannon Westin: So DUO-E was positive for both of its primary endpoints, which was very thrilling. So for the first analysis, which is the durva-alone arm to control, we saw a reduction in the risk of progression of 29%, so a hazard ratio of 0.71. And then the addition of olaparib seemed to further enhance this benefit, so a 45% reduction in the risk of progression for a hazard ratio of 0.55. But what's really exciting is our follow-up time was pretty long; it was about 17 months, so we were able to look at a couple of different analyses, including an 18-month landmark analysis where we saw approximately 50% of the patients were still alive progression free at 18 months, as compared to only 21% of patients being alive progression free in the control arm. So there was a doubling in that progression-free survival time point at 18 months, which is thrilling. Dr. Lidia Schapira: So Ramez, as an expert in the field, what was your reaction when you read or heard these results?  Dr. Ramez Eskander: It's exciting, honestly. So we have gone a long time without seeing really significant successes in the endometrial cancer space, a testament to the fact that we hadn't yet developed our understanding of how we could move this needle forward. But Dr. Westin and the DUO-E team conducted an exceptional clinical trial, as you mentioned, international study, rational and important hypothesis to adjudicate. And what we saw here was both now we had other studies—the RUBY trial, the GY018 trial, the  AtTEnd—and now here DUO-E, which added this hypothesis of PARP maintenance in addition to checkpoint to try to augment response and consistent, really provocative data, exciting, in line with what we've seen and hopefully will continue to drive the science in this space, most importantly. Dr. Lidia Schapira: So let me ask you a follow-up question to that. What kind of scientific questions are in the air now as a result of this trial and what the trial found? Dr. Ramez Eskander: Oh, goodness. Shannon and I could both take this, I'm sure. But I think in the dMMR population, we recognize that there's a ton of data that is supportive of the fact that these tumors are immune responsive, particularly in dMMR endometrial cancer, whether it's an epigenetic promoter hypermethylation, or a mismatch repair gene mutation. I think the data has emerged that immunotherapy is here to stay for these patients in the newly diagnosed advanced stage, even chemo naïve, who need adjuvant therapy.   The pMMR population, this is where we're seeing more and more questions emerge because we realize that that may be a cohort of different cancers. And I'll let Shannon speak to this briefly, but even the incorporation of the PARP inhibitor, in addition to the checkpoint, there's a biologic rationale for combining those two together to augment response. And to see the benefit in that trial—arm three and arm two, we can look at descriptively and look at the differences, but who are those patients? Where is the PARP and the checkpoint most effective? How do we expand that to a larger population of patients potentially? These are questions that emerged because, as Dr. Weston will allude to, I know we also talk about HRR mutations, which are captured, but we even have a lot to understand about that in endometrial cancer, where we've had more research in the ovarian cancer space. Dr. Shannon Westin: Being mindful of time, because I have, like, 1,000 hypotheses that have been generated by this study, which, I think, shows it's a great study, right? Because you get some answers, and as our colleague Brad Monk says, “The only definitive study is the negative studies.” This most certainly was not that. But just kind of expanding on what Ramez said, the interesting thing about DUO-E is that really the biggest benefit for the combination of the durvalumab and olaparib was in that mismatch repair proficient group. And I personally thought that we were going to see accentuation of the impact in the mismatch repair deficient group based on the science, but that just wasn't borne out by the data. It doesn't seem that the combination has that much to add in that mismatch repair deficient group. And when we tease out the mismatch repair proficient group, I think that's where a lot of interesting information is going to come because, to Ramez's point, we're going to tease out: Is it driven by the P53-mutant population? Is it driven by the population that has homologous recombination deficiency? How do we even measure homologous recombination deficiency in endometrial cancer? So I'm super excited about what we found and how that may help us to make those decisions for the patient in front of us.  The other thing I think needs to be made mention of—and this was something we saw in DUO-E as well as AtTEnd—we had a large population of patients that were recruited in Asia, 30%. Interestingly, when we look at the forest plot, that group doesn't seem to benefit as much from the addition of the olaparib. So we really need to tease out what's different about that population because what Nicoletta Colombo presented around AtTEnd, it looked like they didn't benefit from the atezolizumab either in that study. So there's clearly something different about that population, and we have a really big opportunity to look at that since we had such a large proportion of patients that were enrolled there. So that's another, I think, really intriguing question. Dr. Lidia Schapira: So how does this fit in the context of endometrial cancer treatment, and what are we going to do with patients in the clinic? I'd love to hear both of your perspectives, starting with you, Ramez. Dr. Ramez Eskander: It's an evolving answer, to say the least. What we can say definitively is that we have a United States FDA approval for the regimen of dostarlimab plus carboplatin and paclitaxel in the mismatch repair deficient, advanced-stage/recurrent or metastatic patient cohort. And again, that's because the magnitude of benefit that we saw in the RUBY trial, which looked at that, was actually analogous to what we saw in 018, AtTEnd, and DUO-E, again, consistently highlighting the benefit of the IO and the dMMR. We have yet to see how this is going to evolve the landscape in the larger patient population, which is the pMMR patient population. And it may be that based on the data that we have, we will see immunotherapy plus carboplatin and paclitaxel as the new standard of care in the pMMR cohort, or it may not. That's yet to be defined. And I think Dr. Westin will add to this, but I think that's also going to depend on the perception of how we view the cohort. Is it one group of patients? Are we going to have to think about subsets within the pMMR population? That is an active conversation. Dr. Shannon Westin: I would just add, having treated patients on this combo regimen with the durvalumab and olaparib, I have multiple patients that still remain on study, and this—we're looking at three and four years out. I just never saw anything like that before with standard chemotherapy, so there's definitely something here. So I want to know who those patients are, who benefits really the best from the combination, and who could we just give the immunotherapy to and get that same benefit. So we obviously always want people to live as long as possible. That's the bottom line. But we don't want to overtreat. And so I think balancing that is really important. Dr. Ramez Eskander: The point that was made earlier: We have yet, aside from MMR response to checkpoint, within the pMMR population, we understand that there may be subsets, but we have yet to prospectively validate that these molecular cohorts within the pMMR population are truly defining response to a particular therapeutic strategy. So we have to be cautious not to limit the treatment opportunities for these patients without having the data that we need to do so because, as Dr. Westin mentioned, for us—whether it was the Gy018 trial, the RUBY, the DUO-E trial—what we saw is there are pMMR patients who have a dramatic response even though they are “biomarker negative.” They're pMMR, they're TMB low, they're not POLE mutated, but yet they still derive a dramatic benefit. And so that goes back to the hypothesis about why we're even combining checkpoint with chemotherapy in which, for example, in lung cancer, there's been established success and approval. So I think we're all eager to see these strategies emerge as treatment opportunities for the pMMR patients as we work to still develop additional effective opportunities. Dr. Lidia Schapira: So, based on all of this and sort of the new twists on the scientific hypotheses that are now generated, what are the next steps? Dr. Shannon Westin: Well, I think we have to see if these drugs are available for patients. So looking at things like compendium listing and regulatory approvals obviously is going to be very important. But from the things that I can control, we are looking at the different molecular subtypes and understanding the different mutation status and trying to tease out who may be driving the biggest benefits so that we can help advise and make sure that we're doing the right thing for the patients. Dr. Lidia Schapira: And wearing my supportive care hat, I have to ask you, Shannon, about the tolerability. We often find that the quality of life and studies come out after, sometimes months or years after, the original trials are published. So let me take this opportunity to ask you now: How did women tolerate these drugs? Dr. Shannon Westin: The bottom line, Lidia, is, as expected, when you add additional drugs, you see additional side-effects. I think the good thing is that we're very comfortable with immunotherapy and we're very comfortable with PARP inhibition in gynecology because we have had access to these agents and so we know how to manage the toxicities. And so, from a standpoint of incidence, there was a higher incidence of grade three and higher adverse events in the group that had durvalumab/olaparib. But this was primarily driven by anemia, which is as expected and is usually pretty time-limited at the start of olaparib. From a long-term standpoint, there was a slightly higher proportion of patients that discontinued therapy, but it actually wasn't as much as I was worried about. So we saw a 19% discontinuation rate in the group that was just the control arm, and that went up to 24% in the dual arm, so definitely higher, but not that much higher. And when we moved to maintenance, which is really where—that's where the arm becomes unique, it was much lower at about 12%. And so that's exciting to me, that patients were able to stay on a drug and were able to tolerate it.  And then, to your other point, we do have a very nice patient-reported outcomes plan, and that is actually being analyzed as we speak with the hope of presenting it at the next major meeting, our Society of GYN Oncology meeting in March. So not right away, but I think in a pretty timely fashion, we'll have those data. Dr. Lidia Schapira: Congratulations, Shannon, on leading and presenting this wonderful study. So it's been a real pleasure to chat with the two of you. Dr. Ramez Eskander: Thank you. Dr. Shannon Westin: Thanks so much, Lidia. I really appreciate it. Thanks, Ramez, for being here.  And I will just say thank you to all of our listeners. We really hope you enjoyed this episode of JCO After Hours, where we discussed the DUO-E trial, which is a phase III trial evaluating durvalumab plus carboplatin/paclitaxel followed by maintenance durvalumab with or without olaparib as first-line treatment for advanced endometrial cancer. And again, please do enjoy this publication that was online at the Journal of Clinical Oncology on October 21st, 2023. And do check out our other podcast offerings wherever you get your podcasts. Have a wonderful day. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.   Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.      

It's another Landmarks of OncoPharm episode looking at the carboplatin-paclitaxel regimen in ovarian cancer from 20 years ago. carboplatin/paclitaxel vs. cisplatin/paclitaxel: https://pubmed.ncbi.nlm.nih.gov/?term=37643542

The Michigan State University Research Foundation has been enhancing research, encouraging innovation, supporting entrepreneurship, and facilitating economic development through modern commercialization practices, venture creation activity, and innovation partnerships at Michigan State University and across Michigan for 50 years. Executive Director David Washburn reflects on the foundation's history, mission, and impact and on challenges and opportunities ahead for the next 50 years.  Conversation Highlights: (2:26) – “We had flown under the radar for many decades. And when you unpack the story of the foundation, it was like ‘Holy Cow.' There aren't many organizations like this that exist in North America.” (3:02) – “In the late 60s and early 70s, most public universities came to the realization that state support probably wasn't going to be able to keep pace with the growth and expansion of public universities.” (6:13) – “One major inflection point that happened at the foundation was the discovery of Cisplatin and Carboplatin cancer therapeutics.” (7:08) – “Faculty researchers here at MSU discovered a cure for cancer.” (12:07) – “Many faculty in university decided ‘Well, what if we just start new companies and go out and raise venture dollars to see if we can build up a product or service here locally with some local venture dollars?'” (13:30) – “Our focus now at the foundation is in a couple areas. I would refer to them as more venture creation…a lot of states and municipalities are trying to figure out how to create new jobs and an innovation ecosystem. That's the space we're playing in a lot with Spartan Innovations.” (15:40) – “The board approved it and we put together Red Cedar Ventures and have invested in close to 120 start-up companies. We've deployed close to $10 million out of Red Cedar Ventures, and those companies have gone on to raise hundreds of millions of dollars from the venture markets in the state and around the Midwest and on both coasts.” (16:20) – “Between Michigan Rise and Red Cedar Ventures, we have close to $40 million in two robust captive venture funds.” (18:10) – “We built a headquarters for TechSmith because they have a very robust student intern program, and over half of their employees are MSU alumni. They wanted to be closer to campus…They're trying to compete with the Googles and Amazons of the world. And they thought if they had a cool campus, they would have a shot. I think that's helped them.” (18:58) – “We're building spaces so as we start up new companies, not only do we want to help them with their business plan and early-stage funding, but we're trying to find them a home in and around our ecosystem. We think that combination leads to economic development, job growth, and economic diversity. That's really the place where we collaborate and help MSU.” Listen to “MSU Today with Russ White” on the radio and through Spotify, Apple Podcasts, and wherever you listen.

Matt Galski defends cisplatin admirably. 

Lung cancer is one of the most commonly diagnosed type of cancer and so it is fitting that we start the first of our disease-specific oncology series with this diagnosis. This week, we round out our discussion of early stage lung cancer treatment!* When deciding if a patient can get surgery upfront or not, remember the three “Fellow on Call” criteria for early stage lung cancer: - Mass invading other structures or mediastinum- Central lymph nodes (single digit)- Tumor >7 cm* If surgery is NOT an option at this time, where do we go from here?- Treat with upfront concurrent definitive chemoradiation- Treat with “induction” chemotherapy or induction concurrent chemoradiation**If surgery is/may be possible***What are the goals of “induction” treatments? - Eradicate microscopic disease- Improved local control, possibly shrinkage- Adding radiation may allow you to downstage tumor or lymph nodes to have a possible improvement in surgical outcomes* What sorts of discussions are being had a thoracic tumor board in patients with newly diagnosed early stage NSCLC? - Is the patient a surgical candidate?- If the patient is not a surgical candidate, then what are the options:--Definitive concurrent chemoradiation (usually) followed by immunotherapy---Pearl 1: Always choose this if surgeon thinks the patient is unresectable in general even with an induction approach---Pearl 2: Always choose this if 2 out of 3 criteria we discussed above are met---Pearl 3: Always choose this if N3 disease- “Induction” regimen with either chemotherapy alone or concurrent chemoradiation followed by surgery * What's the idea behind “induction” chemo or chemoradiation? - There is a chance that patients with these high risk features may already have micrometastatic disease, so treatment upfront can help address that- There is a chance that after surgery, patient may suffer deconditioning, which may preclude the use of chemo +/- radiation (up to 90% of patients are often eligible for chemoradiation before surgery; this drops to ~60% after surgery)- Local disease control to achieve the best possible surgical outcome (R0 resection) and also prevent any microscopic residual disease from then having the opportunity to spread systemically, especially in areas where the mass may be adjacent to many blood vessels or lymph nodes* What to treat with in the neoadjuvant setting?- Platinum containing regimens (“platinum doublets”):-- Carboplatin + paclitaxel-- Cisplatin + etoposide-- Cisplatin + gemcitable-- Cistplain + pemetrexed- Can combine this with radiation* How does the data about chemotherapy+IO in the neoadjuvant setting fit in here (CHECKMATE 816)?- In patients with Stage IIB to IIIA (8th edition) WITHOUT EGFR or ALK mutation, treatment with NEOADJUVANT chemotherapy q3w x3 cycles (most got cisplatin based therapy) + nivolumab 360mg q3w x3 cycles resulted in improved event free survival (31.6 months vs. 20.8 months) AND pathological complete response was 24.0% vs. 2.2%- Current NCCN guidelines state that if nivolumab is used in neoadjuvant setting, it should not be used in adjuvant setting- There is still uncertainty about how this fits into treatment compared to “traditional” neoadjuvant approaches with chemo+/-radiation*So after neoadjuvant treatment, does everyone go to surgery?- Always re-assess the status of the disease; if there is progression of disease, then will go to definitive chemoradiation- Discuss with surgeons to confirm if the patient is still a surgery candidate* If patient undergoes surgery, then what?- If patient got neoadjuvant therapy and an R0, then they are done with treatment- If R0 resection was not able to achieved, then either radiation “boost” to the area (if they previously got radiation), a course of radiation (if they just got induction chemo) or re-resection- We discuss the adjuvant setting in more detail in Episode 026 (https://www.thefellowoncall.com/tfocpodcast/episode-001disclaimer-wfhgf-ml3b6-9m66a-8rrc4-k8w87-x7xdd-wrzye-4xg8x-t73gt-cxc5s-nmg8f-cfyd6-hgs35-5pcwx-tf6dh-trggt-xzkt7-923gg-rpjzx-6s36p-hk27n-bbpgx-jymml-9lfam-76m4s)** If surgery is not possible*** If patient cannot go through to surgery Definitive chemoradiation:- Same chemotherapy agents as above, but treatment course is longer.- For instance, for NSCLC, total 60Gy in 2Gy divided fractions (5 days/week, 6 weeks of treatment) with chemotherapy* Additional therapy after chemoradiation (PACIFIC Trial) - Found that “consolidation” durvalumab 44% PFS 18 months vs 20% 5year survival benefit 40% vs. ~30% without treatmentReferences:https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1450 - NCCN Lung Cancer guidelines https://www.nejm.org/doi/full/10.1056/nejmoa1709937 - PACIFIC Trial (NEJM 2017)https://www.nejm.org/doi/10.1056/NEJMoa2202170 - CHECKMATE 816 (NEJM 2022) Please visit our website (TheFellowOnCall.com) for more information Twitter: @TheFellowOnCallInstagram: @TheFellowOnCallListen in on: Apple Podcast, Spotify, and Google Podcast

On the eve of her first chemotherapy infusion, Natasha hauls a pile of new prescriptions home and questions why so much harm must be done to be “healthy” again. After meeting her oncologist Dr. Chen, a specialist in HER-2 positive breast cancer, the clinical trial that originally sounded promising turned out not to be a good fit, leading to a much less invasive chemo recipe consisting of Taxotere, Carboplatin, Herceptin, and Perjeta spaced three weeks apart, but thankfully no need for Taxol. To save her hair from falling out, Natasha's dad graciously volunteers to cover the cost of cold caps (thanks Neil!) but the tradeoff is additional logistics, longer appointments on the chemo days, and no guarantee that it will work. Links Support the Breast Cancer Stories podcast https://www.breastcancerstoriespodcast.com/donate Subscribe to our newsletter here: http://eepurl.com/hX12YD Other Links Support the Breast Cancer Stories podcast https://www.breastcancerstoriespodcast.com/donate Subscribe to our newsletter here: http://eepurl.com/hX12YD About Breast Cancer Stories Breast Cancer Stories follows Natasha Curry, a palliative care nurse practitioner at San Francisco General Hospital, through her experience of going from being a nurse to a patient after being diagnosed with breast cancer. Natasha was in Malawi on a Doctors Without Borders mission in 2021 when her husband of 25 years announced in a text message that he was leaving. She returned home, fell into bed for a few weeks, and eventually pulled herself together and went back to work. A few months later when she discovered an almond-sized lump in her armpit, she did everything she tells her patients not to do and dismissed it, or wrote it off as a “fat lump." Months went by before Natasha finally got a mammogram, but radiology saw nothing in either breast. It was the armpit lump that caught their attention. Next step was an ultrasound, where the lump was clearly visible. One painful biopsy later, Natasha found out she had cancer; in one life-changing moment, the nurse became the patient. This podcast is about what happens when you have breast cancer, told in real time. Host and Executive Producer: Eva Sheie Co-Host: Kristen Vengler Editor and Audio Engineer: Daniel Croeser Theme Music: Them Highs and Lows, Bird of Figment (https://music.apple.com/us/artist/bird-of-figment/1434663902) Production Assistant: Mary Ellen Clarkson Cover Art Designer: Shawn Hiatt Breast Cancer Stories is a production of The Axis. (http://www.theaxis.io/) PROUDLY MADE IN AUSTIN, TEXAS

Picture this: it's day 1 of fellowship and your attending needs you to "get consent for treatment." Huh? How do you educate your patient? We share our tips! In this episode, we discuss important considerations, including “does my patient need a port?”, “what if drugs extravasate?”, “how do I keep side effects of drug classes straight?!” *The resources we share are our OWN opinions. Naming of resources are not endorsements. We are not sponsored by any of these entities. Pharmacology 101: * Irritant vs. Vesicant:** Each drug is deemed one of these based on the degree of tissue damage that can result if drug extravasates under skin. 
** Vesicant: needs central access
** Irritant: can be given peripherally 
* Does my patient need a port/picc?** If vesicant; for continuous infusions over several days (e.g. 5-FU); some patients with difficult access may request. 
*Advantages of ports: ** Easy access for labs
** Easy access for chemotherapy/fluids
* Disadvantages: ** Risk of infection
** Risk of thrombosis 
* General overview of chemotherapy side effects: ** Going to target the fastest growing cells in the body, which includes cells that line the GI tract, skin, hair/nails, and blood cells
** Therefore side effects are related: *** GI: nausea/vomiting, diarrhea (sometimes constipation), decreased appetite, taste changes
*** Low blood counts **** WBC nadir ~10-14 days (generally), and recover 21-28 days after chemo
* What about unique side effects of chemotherapy classes? How do we keep them straight?** We love keeping “Chemoman” from the USMLE study days in mind!
* Anthracycline*** MOA: Topoisomerase inhibitors
*** Ends in “rubicin”
*** You might hear people call doxorubicin the “red devil”
*** Used in lots of cancers
*** Hair loss occurs with this one
*** Known to cause cytopenias and associated with higher nausea potential 
*** Unique side effects: **** Heart failure (always get baseline echo!)
**** Development of MDS and leukemia 
* Alkylating agents** MOA: Drugs add alkyl group to the guanine base of the DNA molecule, preventing linking of strands
** End in “fosfamide”
** fosfamide or cyclophosphamide (AKA cytoxan)
** Used in lots of cancers
** Known to cause cytopenias and hair loss
** Unique side effects:*** Secondary MDS or leukemia possible 
*** Ifosfamide = neurotoxicity = methylene blue antidote
*** Cyclophosphamide = hemorrhagic cystitis due to acrolein byproduct accumulation = prevent by giving mesna to protect bladder
* Antimetabolites** MOA: Purine analog, pyrimidine analog, folate antagonists; therefore prevent production of base pairs or binds instead of normal base pairs
** End in “abine” - capecitabine, cytarabine, gemcitabine, cladribine, fludarabine
** Also 5-FU and 6-MP in this category so “number followed by dash”
 ** Unique side effects:*** Think bone marrow suppression in this category 
* Platinum agents** MOA: Believed to cause cross-linking of DNA
** End in “platin”
** Associated with high risk of neuropathy 
** Unique side effects: *** Cisplatin: **** Nephrotoxicity 
**** Ototoxicity 
**** High risk of nausea; need special prophylaxis 
*** Carboplatin: cytopenias
*** Oxaliplatin: higher rates GI side effects 
* Microtubule agents** MOA: Impair microtubule function, therefore impacting cell division
** End in “taxel” or vincristine/vinblastine (“V-stine”)
** Unique side effects: Neuropathy
Please visit our website (TheFellowOnCall.com) for more information Twitter: @TheFellowOnCallInstagram: @TheFellowOnCallListen in on: Apple Podcast, Spotify, and Google Podcast

Your listening experience is extremely important to us with that being said please forgive Kristine's audio track. We apologize and will continue to work to improve your overall experience. Thank you for helping us bridge the gap between rare diseases and the rest of the world._____________________________________________Meet Kenzi: I had a positive pap in 2016, got a biopsy and found out it was stage 1 cancer. I was told I had HPV 16 and that's what had caused my cancer. I Had a colposcopy, got it lasered & was good to go. I was supposed to have semi annual paps but didn't go. I had 5 babies (two after the first diagnosis) and got wrapped up in life and never made Pap smears a priority. I didn't know it was important.. I didn't go get a Pap after my last daughter was born.After four years of not getting a Pap smear, I went in in September 2020..i had a positive pap and dysplasia was found.they did a colposcopy and biopsy. Staged me at 3b. I did a leep procedure. I went through two rounds of chemo (Carboplatin and paclitaxel) and internal/external radiation. And they took me back very quick to get a total hysterectomy. The next pet scan showed two of my pelvic lymph nodes were being effected.So I had a second surgery.. I got para-aortic lymph nodes dissection. A week after that surgery I went to the hospital for pain and they found out I had an internal secondary hemorrhage. They did a surgery for packing and vault suturing. I also required a blood transfusion. (I'm anemic anyways) Following that I had surgery for a cuff tear that required a revision. After that I developed cuff cellulitis infection. I was hospitalized with Iv antibiotics. I got my last a pet scan in April 2021 and The surgeries were successful to get rid of the cancer. My scan was clear. I had to go in every 3 months for a check up scan (CT or PET) my husband got out of the military and we moved from California to Michigan to buy our first house. I set up my follow up appointment. It NEVER crossed my mind that the cancer could be back.. I was determined and had plans to live life cancer free. Due to my Covid symptoms they called me and read to me my results. I had a 5.6 cm tumor in my pelvic/abdominal wall cavity. Biopsy came back cancerous. I started chemo right away. They sent me to a surgeon. He took me back for my 6th surgery. Performed Debunking & small bowel resection. Tumor was removed en bloc, with 2 segments of small bowel. The surgeon anticipates 3-5 more surgeries. After that, I had went to the ER for breathing struggles and they had found a nodule on my left lung. I just got a biopsy recently and am waiting for my results. I also go talk to the surgeon next week to discuss more surgeries. In the meantime i have gotten Covid (for the second time) I've have had to wear a 24 hour heart rate monitor. I have severe vertigo and was passing out. After hitting my head numerous times, they Diagnosed me with post concussion syndrome. The dr found out why it was happening and diagnosed me with POTS..and I have a vitamin b 12, vitamin d, magnesium and potassium deficiency which I am taking medicine for now. I'm already anemic and have needed multiple blood infusions through the last couple years.I'm just happy and thankful to be at home right now with my family instead of living in the hospital._____________________________________The CUBE and OOLER systems are two really cool gadgets that fit over the top of your mattress and use water to control the temperature of your bed. Right now Chili is offering my audience a really great deal. When you go to Chilisleep.com/findyourrare20, you can get 20% off the CUBE all sleep systems with findyourrare20. I hope you'll check out Chili and see why I love their products so much.Support the show

When Heidi Slansky survived Stage III breast cancer AND skin cancer, she wanted to come to the aid of female cancer survivors in the Dallas-Fort Worth area.  Inspired by slipping on boxing gloves and how they made her feel like she was truly fighting cancer, Heidi founded Cancer StrongHER.  Its mission is to help women physically and mentally by provided a forum to actively carry the fight through boxing fitness, tae kwon do, yoga and pilates.  At all times, the classes she offers are free of charge.  Those outside Dallas-Fort Worth can learn more about what Cancer StrongHER has to offer by checking out its website, www.cancerstrongher.org.

Tripawd Talk Radio Episode #105: On this episode we talk with Dr. Brooke Britton about combination therapy for dogs with osteosarcoma. Specifically, we discuss her monthly chemotherapy treatments with both Palladia and Carboplatin for Jake – a 14+ year old three legged German Shepherd mix.Topic: Combination therapy for canine cancer, including Monthly Chemotherapy for Dogs with Osteosarcoma (and other innovative limb cancer therapies) Our Guest: Brooke Britton DVM DACVIM (Oncology) is a board-certified veterinary oncologist based in New York City.  A New York native, Dr. Britton obtained her veterinary degree from Cornell in 2007.  After completing her residency training at the University of Pennsylvania in 2012, she returned to New York and practiced at BluePearl Veterinary Partners for several years.  She is now a private consultant.  Dr. Britton focuses on providing proactive, cutting edge, evidence-based therapy for companion animals, with an emphasis on maximization of quality of life during treatment.Resources mentioned in this episode:Tripawds News: Veterinary Oncologyhttps://tripawds.com/tag/oncology/Jake's Story:https://tripawds.com/forums/treatment-and-recovery/one-year-after-front-leg-amputation-from-osteosarcoma-more-info-on-chemo-therapy-combo-carboplatin-palladia/Watch Episode Video:https://youtu.be/Dm3Z78aLQFgFind All Tripawd Talk Radio Episodes & Subscribe:https://tripawds.com/radioSupport the show! (https://tripawds.com/support)Support the show (https://tripawds.com/support)

Immunotherapy is transforming the treatment landscape for triple-negative breast cancer. Through patient cases, Drs. Ruth O'Regan (medical oncologist, University of Rochester) and Jacob Kettle (Pharmacist, University of Missouri) discuss the application of novel treatment options. Subscribe: Apple Podcasts, Google Podcasts | Additional resources: elearning.asco.org | Contact Us Air Date: 8/18/2021   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and inform. This is not a substitute for medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. RUTH O'REGAN: Hello and welcome to ASCO's Education Podcast episode, focused on new therapies for triple negative breast cancer. My name is Ruth O'Regan. I'm a medical oncologist and the Chair of Medicine at the University of Rochester. JACOB KETTLE: And I'm Dr. Jacob Kettle. I'm an oncology clinical pharmacy specialist and pharmacy manager at University of Missouri Health Care's Ellis Fischel Cancer Center. We'll start our discussion today with a patient case. So let's say we have a 64-year-old female diagnosed with stage two triple-negative breast cancer three years ago. She received neoadjuvant AC-T and then underwent mastectomy, followed by adjuvant capecitabine. One year after completing therapy, she presented with new neck masts. Imaging demonstrated cervical nodes, probable liver metastases, and lymph node biopsy confirmed suspicion of recurrence, and now metastatic triple-negative breast cancer that is PDL1 positive. So Dr. Regan, what, in this patient, would you be considering for therapy for her. RUTH O'REGAN: Yeah, so I think unfortunately this is a pretty typical history of a patient with triple-negative breast cancer having this recurrence within two to three years of diagnosis. So her cancer is PDL1 positive, so obviously that would mean that we would consider immunotherapy for this patient. And there are two options with regard to this. We can either use atezolizumab or pembrolizumab plus chemotherapy, which could be paclitaxel, nab-paclitaxel, or, indeed, gemcitabine and carboplatin. So just to very briefly review the trials-- so the IMpassion 130 trial randomized patients in the first-line setting with metastatic triple-negative breast cancer to nab-paclitaxel weekly with or without atezolizumab, and it showed a benefit and progression-free survival of about two months in patients whose cancers were PDL1 positive, and also an overall survival advantage that was quite meaningful at about seven months in the patients who received the immunotherapy plus nab-paclitaxel compared to the control arm. So that obviously would be a very reasonable option for this patient. The KEYNOTE-355 trial evaluated chemotherapy, which could be paclitaxel, nab-paclitaxel gemcitabine, carboplatin, with or without pembrolizumab, again in the first-line setting for metastatic triple-negative breast cancer. And so really, very similar results to the IMpassion study with about a two month improvement in progression-free survival in patients whose cancers were PDL1 positive. What we'll talk about later on is how we define PDL1 positivity in this patient population. JACOB KETTLE: Yeah, I think that's an important distinction. RUTH O'REGAN: Yeah, I think we can talk about that, because I think most of us now are actually doing both of the assays. But on the face of it, in somebody who has a cancer that's PDL1 positive, I'm not sure that there's a huge difference. Obviously you can't do cross-trial comparisons. I tend to use atezolizumab plus nab-paclitaxel because that was the first one that was approved. But I also think, in a patient who's had a recent taxane, using pembrolizumab plus gem/carbo would also be very reasonable. The other trial I was just going to mention was the IMpassion 131 trial. JACOB KETTLE: Yeah, absolutely. It's a game changer. RUTH O'REGAN: It really is, because in that study they use paclitaxel with or without atezolizumab and actually didn't see an advantage for the immunotherapy, even in patients with PDL1 positive cancers. We really don't know why that is, but it's definitely an interesting finding. JACOB KETTLE: I mean, I think that really speaks to the importance of sticking with what we know from the trials. RUTH O'REGAN: Absolutely JACOB KETTLE: I think there's a tendency, especially with pembro's FDA approval, says chemo. Just-- that's it, chemo. But the trial, as you mentioned, limits it to paclitaxel, nab-paclitaxel, or the combination of carbo and gemcitabine, but really to extrapolate that to other chemo regimens, other drugs, I think that's a little bit of a stretch. Because, again, we saw an IMpassion 131, maybe it's not, across the board, efficacious. There may be some subtle differences there. I'm glad you brought that up, because I think that's an important distinction. RUTH O'REGAN: It's all about following the data. I think that's a key thing. So Jake, just in your role as a pharmacist, I think will be very interesting for you to talk a little bit about toxicity of these agents, and if there's any difference in the safety profile between these agents. JACOB KETTLE: Yeah, I think what we've seen is pretty consistent as really all our experiences. We've started combining immunotherapy with chemotherapies that really it's not this new emergence of unexpected toxicity or an unacceptable level of toxicity. It's just what we would expect with chemotherapy agents and what we've already known with immune therapy agents. So there's nothing new and emergent or difficult to deal with. And from the IO toxicity profile, it's all the same stuff we're used to. Derm toxicities, GI, pulmonary, endocrinopathies for the most part. We are comparing to PD1 inhibitor in pembrolizumab to PDL1 inhibitor in atezolizumab, so maybe there are some subtle differences. I think some of the things I've read have suggested maybe endocrinopathies are potentially more likely with PD 1 inhibitors. But these are all subtle things, very nuanced-- I don't think anything that would really dictate a difference in choice of therapy. So I think from the side effect profile, fairly interchangeable, at least from the immunotherapy perspective. Obviously, we're talking about the biggest difference is the chemo backbone, and that's going to be a key driver in what regimen you pick. Again atezolizumab-- very limited to the nab-paclitaxel backbone, which is great drug. Like you said, it was the first out. And I think another important caveat is that is the only trial in this space where we have overall survival data. We don't see that yet in KEYNOTE-355. Although, as you pointed out, PFS looks very similar between the two. So we anticipate-- don't extrapolate too much, but anticipate those are, efficacy-wise, pretty interchangeable. But the chemo backbone-- big difference between the two. Again, you have a little bit of flexibility of pembrolizumab to use paclitaxel, nab-paclitaxel. Or I think, again, for those patients that have recently exposed to paclitaxel-- it kind of fits with our case. This patient-- relatively early relapse, pretty early recently exposed to taxanes in the neoadjuvant or adjuvant space, you may want to use a different regimen. Carboplatin and gemcitabine-- a great commonly used triple-negative backbone, especially again, if you have those folks with more disease burden, visceral disease, where you want to get that bigger punch up front. I think that's another potential role there. But one other thing is to talk about logistics. These kind of regimens are very different because of how the immunotherapy is dosed. So when we use atezolizumab with nab-paclitaxel, that aligns very nicely with a 28-day cycle. Atezolizumab on day 1 and 15, nab-paclitaxel on day 1, 8, and 15. An off day at 22 that flows really nicely. Pembrolizumab, when you combine it with carbo and gemcitabine, that aligns really nicely with the 21-day cycle. Again, pembrolizumab on day 1, carbo, gem, day 1 and 8 and off day of 15. The regimen that gets a little funky, for lack of a better word, is when you try to combine pembrolizumab with the taxane, because the taxanes kind of line up on a 28-day cycle, days 1, 8, and 15. And pembrolizumab is a 21-day cycle. So that could become a little bit cumbersome to navigate those waters and get those doses the right days. So you can just, from a logistical perspective, I think there's some differences there. And the challenge really is, how do we kind of get this nice balance of finding the treatment regimen that's compatible with the patient's lifestyle, the monitoring frequency, and just your clinical operations to make sure all those things align? And we do want to have some flexibility. I think that's one of the great gifts in modern oncology, is we have all these good choices, but both are really important. You also want to have some consistency. So anyway, that's a really long-winded answer to side effects. I don't think there's much difference, in terms of side effects. RUTH O'REGAN: I think your point is very important. Because this is all about the patient, of course. Because we've got metastatic triple negative breast cancer. So I think making it as painless as possible for them to come in, as far as their scheduling, I think, obviously, is very important. Now, I think one of the issues with the immunotherapy is that I don't think we got great biomarkers. So we use PD-L1, but really, it's imperfect. And as we kind of alluded to earlier in the IMPASSION study, they used PD-L1 on the immune cells as a marker, and about 40% of the cancers in that study were determined to be positive. And that's where the benefit was seen. In contrast, in the KEYNOTE study, they used what I think a lot of, outside the breast cancer world, is being used a lot, is this CPS, or Combined Positive Score, that basically looks at the PD-L1 positive tumor cells and immune cells and basically looks at them compared to the overall number of tumor cells. So at this point, we're kind of in a situation where we have to kind of check for both. The interesting thing that's been shown is that there's not complete overlap. It's only about 75%. So it is possible that you could have a cancer that was PD-L1 positive by one of the assays, but not by the other. And I guess that might help us decide which agent to use, although I've never seen that myself in my practice. But I don't know what your experience with that is. It would be nice to have a better biomarker, I think. JACOB KETTLE: Yeah, I'm glad you brought that up. Because I would be in the same boat. I haven't seen a case, but obviously it's possible to have some discordance. And we're looking at PD-L1 expression, whether you're looking at the tumor, or you're looking at expression in a combined positive score, regardless of the assay, it's on a scale. It's not a yes or no question. And little, subtle differences can be the make or break between determining whether someone's PD-L1 positive. I've heard-- and I don't want to comment too much-- but there could be discordance whether you're testing archived tissue, whether you're testing metastatic tissue, maybe some differences between what site the metastatic disease was found in. Did you find it in the liver? Did you do the biopsy from the lymph node? Again, that all speaks, it goes back to the imperfection of PD-L1 as a biomarker. It's just kind of this dynamically unstable marker that's not as predictable and not as viable as some of the other biomarkers we use. And we want to take advantage of it as much as we can, and find as many unique treatment options for patients, but also don't want to leave-- we don't want to leave anything on the table. RUTH O'REGAN: And I think the other interesting thing that we'll talk about later is that PD-L1 doesn't appear to be a biomarker at all in the earlier stage setting, which is, I think, very interesting. I think one of the things that's worth mentioning is that, of course, some patients do incredibly well with immunotherapy and have very, very prolonged responses. So trying to work out who those patients are, I think, would be just incredibly valuable. I have a couple of patients that actually came off the immunotherapies because of immune toxicity, but have remained, really, in remission for years after that, even though they actually weren't even receiving the drug. So it's really fascinating. I think the other thing, though, is unfortunately, the majority of patients do not have cancers that are PD-L1 positive. And I guess the question is, what would we do for those patients? And the only really standard is chemotherapy. And I guess I'd be interested in your thoughts on, is there a preference first-line chemotherapy that would be used in your practice, or what are your thoughts on that? JACOB KETTLE: I'd more defer to you on answering that. As far as our practice, you kind of have the whole mix of what you can pick from. You've got taxanes. You've got anthracyclines. You've got gemcitabines. We've got capecitabines of the world. Eribulin is a fantastic drug. Again, a lot of that goes back to what's best for the patient. And I think that is, again, the miracle. It's a challenge, because we all of a sudden have all these options, but it's the great blessing in practicing in oncology today, is there is this wealth of options, and we have the potential to really guide therapy to what's preferential to the patient. RUTH O'REGAN: Yeah, I completely agree with that. And my thought always has been-- and I think this is very much in keeping with the NCCN guidelines-- is that there isn't a huge difference, in terms of efficacy. So I actually quite often use capecitabine in these patients, even though there was some data at one point saying that maybe capecitabine wasn't as effective in ER-negative breast cancer. I think we know that's not true in actual fact. So I think that's a great option. If they haven't had a taxane, either paclitaxel or nab-paclitaxel is a good option. And then I think if somebody's got a large burden of disease, using a doublet like gemcitabine and carboplatin is totally reasonable, as well. Obviously, thinking about clinical trials, and particularly once you get past the first line setting for these patients is very important. And I think one of the complexities about triple-negative breast cancer is the fact that there's at least four different subtypes that probably do require slightly different approaches. But at this point, that's not really standard of care. We kind of just manage them all the same way. But I think that's what's kind of on the horizon, as far as selecting at the best option for patients. I think one very interesting subset is the subset that expresses androgen receptor, and which I think initially, we were super excited about. And I still think it's very interesting, but so far the data looking at antiandrogens in these cancers has not been that impressive, although there are some patients that benefit. JACOB KETTLE: Well, I do think, too, the immunotherapy story, we kind of got talking about biomarkers. Even if you're not PD-L1 positive, even if the tumor doesn't express PD-L1, that's not necessarily the end of the role of immunotherapy in breast cancer. KEYNOTE 119 showed that pembrolizumab monotherapy later on didn't work, but we still need to be assessing for tumor mutation burden, microsatellite instability or mismatch repair. Those are other avenues by which we do have some good data to support that there is a role for immunotherapy in breast cancer, these triple-negative breast cancer patients. Like you said, only about 40% are going to be PD-L1 positive. So that leaves 60%, more than half the pie, that are going to not have a route for immunotherapy. So I do think it's important that we always explore tumor mutation burden and microsatellite instability. Because again-- and you've alluded to this-- the great promise of immunotherapy is this potential for really long, sustained responses. And until we have really good predictive tools to find exactly what patients are going to be that, I think we should be striving to at least offer that glimmer of hope, that potential opportunity to as many patients as we can. But I think it's another important part of breast cancer is that, again, immunotherapy doesn't start with PD-L1. That's just a sliver of the useful biomarkers here. RUTH O'REGAN: I completely agree with that. I think for our patients, it's important to consider sending tumor genomics, for sure, for exactly the reason that you said. I'm obviously also doing genetic testing to see if they've got a BRCA1 or BRCA2 mutation, or indeed a PALB2 mutation. Now there's some data suggesting that PARP inhibitors might actually be effective with those germline mutations as well. So I think definitely, sending that off makes sense. Unfortunately, as we know, in triple negative breast cancer, we don't very often see actionable mutations. We see them, I think, more commonly in ER-positive breast cancers. But certainly we're ascending, I would think. JACOB KETTLE: Excellent. I think that was a great discussion. Let's shift gears and do a second case and talk a little bit about this emergence of immunotherapy in the upfront setting, in the neoadjuvant setting. We'll talk about that a little bit, and then what are some additional later-line options? So we'll do our second case. This will be a 45-year-old female presents with relapsed/refractory triple-negative breast cancer, metastatic disease in the bones and liver. Her initial therapy consisted of neoadjuvant chemotherapy combined with immunotherapy. And that would be what was discussed in the KEYNOTE 522 trial. So before talking about choice of therapy for this patient, let's dive in a little bit about and talk about KEYNOTE 522. What are your thoughts of up-front immunotherapy in triple-negative disease? RUTH O'REGAN: So KEYNOTE 522 took patients with earlier stage triple-negative breast cancer and basically randomized into the standard anthracycline taxane-based chemotherapy with or without pembrolizumab, and actually showed pretty impressive pathologic complete response rate in the immunotherapy arm. It's about 65%, and it was quite a bit higher than the control arm, where it was about 50% or so. And they actually have some data as well looking at event-free survival showing a benefit for the addition of pembrolizumab. It's not FDA approved yet. And obviously, you have to take into account toxicity, which I'd certainly like to get your thoughts on. But I think we know that pathologic complete response is very important, a prognostic factor in triple-negative breast cancer, at least in most subtypes. So getting a pathologic complete response rate that high, I think, is very important. And I have to say, I tend to reserve this approach for patients who have clinically node-positive breast cancers or locally-advanced breast cancers. Because-- I should have said this earlier-- because in KEYNOTE 522, all the patients got carboplatin as well. And that's one of the problems, I think, because it's hard to add carboplatin with paclitaxel. Just to mention that we also, at ASCO, just heard a follow-up of the GeparNuevo study that looked at durvalumab with a slight, somewhat similar anthracycline taxane-based regimen. They saw a higher pathologic complete response rate in the durvalumab arm. But actually, we're showing data, now, on longer-term outcomes, and again showing a benefit for the immunotherapy. So it is interesting. I think you're always weighing up longer-term toxicities with the efficacy seen here. But I think with a pathologic complete response rate that high, I think in a patient who has more higher-stage triple-negative breast cancer, I would consider adding pembrolizumab for that patient in this setting. But I guess I'd like to hear your thoughts on weighing up toxicity. It's a little bit different in this scenario versus the metastatic setting, I think. JACOB KETTLE: I completely agree with you. That PCR rate is supremely promising. Obviously, we need time for the data to mature. But I think there's definitely a subset of patients that I think we're going to find this, hopefully, to be very beneficial. And triple-negative disease is problematic, so any additional tool is useful. But again, it's a very intense chemotherapy backbone. Four cycles of carbo-paclitaxel, and then four cycles of an anthracycline and cyclophosphamide base with pembrolizumab throughout the whole cycle, that's not going to be something that all patients are going to be able to tolerate. So again, as the data matures, my hope is that we can really narrow in on the subset of patients that this is most likely to really deliver a lot of benefit to. And I've probably said this three or four times already, but I really didn't feel like this is the great promise. But again, the great challenge of oncology practice today is, we're going to end up with four or five different great options for up-front therapy in neoadjuvant or adjuvant treatment, and it's really going to be up to us to really tailor therapy and find this ideal balance of risk and benefit ratio to meet patients' needs, and what they value. And so some patients may have, they want to avoid the severe toxicities at all costs. And that's maybe how we pursue, is to get the best benefit with that in mind. And then you'll have patients that will say, I'll go through anything. I want my risk of relapse be absolutely as low as possible, and I'll take all the chemo you're willing to throw. And trying to figure out how to walk that line, I think, is our challenge. So with that in mind, remember back to our case, our second case here, we're going to assume that this patient's relapsed after immunotherapy in the front line. And I think that is another thing we'll explore, as the years go by, is learning, what do we do when we start seeing these therapies early in treatment, whether it's breast cancer or other tumor types? But what would your approach be, if they did relapse after initial immunotherapy? RUTH O'REGAN: Well, I think this is a data-free area. And I should have said when I was talking about the earlier phase studies that PD-L1 is not a biomarker in that scenario. So if we assume this patient has PD-L1 positive cancer, I guess it would really depend on how long it was since she got the neoadjuvant chemotherapy. But I could envision if she was a couple of years out, I might think about rechallenging her, particularly with a different PD-L1 or checkpoint inhibitor. But I think that's not the likely scenario, because most of these patients will have pretty high-stage disease when they present, and they probably relapse pretty quickly. So I guess we're kind of back to the case we talked about earlier, where you're really looking at the different chemotherapy options. So I think there is a potential for rechallenging with immunotherapy. I don't know-- and you may know this-- if there's any data outside of breast cancer, like lung cancer, where this has been done, for example. I'm just not aware of that data. JACOB KETTLE: Yeah. I'm not aware of any really solid evidence. I think you can find anecdotal reports or some retrospective studies that do suggest maybe it's beneficial. And I think, especially like you mentioned, for someone with a nice long response, good, strong tolerability, all those kind of things, may be worth considering. But again, the challenge with immunotherapy, it doesn't work quickly. So you always have that component. And like you said, these are aggressive, rapid relapses. That may not be something you can lean on too heavily. So I think it all speaks back to, we're very confident in pathological complete response as a very strong surrogate marker for long-term benefit. But again, we're using it in a slightly new space. And until that data is very mature, and we have the overall survival data, what we don't know is, how does this all translate to the whole picture for the patient? If we burn out of immunotherapy up front, I don't know. Does that mean it's not useful, and we've lost lines of therapy in the relapse/refractory setting? I don't know. Those are some of the big questions we have. RUTH O'REGAN: And I think it also speaks to what you said earlier, that the whole immuno milieu of the cancer may change, depending on what setting you're looking at. So there could be very good rationale for rechallenging with immunotherapy. But again, I think this is an area where we really would need some data for sure. JACOB KETTLE: Yeah, absolutely. Very tricky. So let's play out the scenario just a little bit more. Let's say we started carboplatin and gemcitabine, for instance, in this patient. She got about nine months of therapy, and then progressed again. What other, maybe, newer options are lingering out there for sort of later-line triple-negative metastatic disease? RUTH O'REGAN: So unfortunately, of course, that's typically what you see. They usually, patients usuallt experience disease progression within six to nine months. And so obviously, alternative chemo options would be on the table, a taxane, if she hasn't had one recently, capecitabine, if she hasn't had that. However, I think for a patient like this, I would strongly consider sacituzumab, which is a relatively new antibody drug conjugate that targets Trop-2. The data from the ASCENT study, which looked at patients with triple-negative breast cancer who'd had at least two prior lines of treatment were randomized to sacituzumab or to physician's choice of chemotherapy, and the data was pretty striking. And the progression-free survival, it was less than two months in the control arm, versus six months in the sacituzumab arm. But the overall survival was doubled from six months to 12 months by using sacituzumab. So that's pretty impressive in this scenario. And it appears that, although most triple-negative breast cancers do express Trop-2, there doesn't appear to be a definitive correlation between Trop-2 expression and benefit from this drug. So there appears to be some kind of a bystander effect from this antibody drug conjugate. I think it's a really interesting drug, and maybe you can talk a little bit about the tolerability of it. JACOB KETTLE: Yeah. So again, like you said, it's a Trop-2 target. That's the antibody component. And Trop-2 is a transmembrane glycoprotein. It's upregulated in a lot of tumor types. So this is not something that you necessarily would do additional testing for. It's not unique to breast cancer. And sacituzumab-govitecan has an approval now in bladder cancer as well. So I think we're going to start seeing more emergence and utilization of Trop-2. And then like you said, it's kind of an enriching biomarker. You might see a slightly higher response rate for those overexpressors. But again, low expressors still respond. But I think when it comes to the side effect profile-wise, it was all driven by the chemo payload. And that's Govitecan, or SN-38. This is the active metabolite of irinotecan. And so a couple of things make this really exciting to utilize in breast cancer. One is, we're all probably fairly familiar with managing the common side effects of irinotecan, predominantly neutropenia and diarrhea. So we don't have to relearn or come up with a new kind of management profile, side effect-wise. But I think part of why we see such a robust response is this is a mechanism of action. Govitecan, it's a topoisomerase inhibitor that almost, I'd say, the vast, vast majority of breast cancer patients have not been exposed to that mechanism at any point in their treatment journey. So you take advantage of that new option. And I think, all things considered, this is why we've seen this kind of recent-- it's not brand new technology-- but we've seen this recent emergence of a lot of antibody-derived conjugates. Because it really does allow you to take advantage of antineoplastic agents that may otherwise be too toxic, but we find a way to deliver it in a very sophisticated, precise manner. And by doing so, again, we're able to take advantage of chemotherapeutic agents that otherwise would be on the shelf. But we can deliver it in a very precise way. And so that's a really exciting piece of the promise for this drug. And again, just to ask you, do you any anecdotal experience or insights with the drug? RUTH O'REGAN: Yeah. I've used it a little bit. I actually started a patient on it today. But overall, I think it's well tolerated. It's unfortunate it causes alopecia, obviously. But I think most patients with the results of the ASCENT trial, they're OK with that, I think. And the tolerability seems to be very reasonable. JACOB KETTLE: I mean, a six-month OS improvement at this stage of the game is pretty clinically meaningful. RUTH O'REGAN: I don't think we've really seen that before, actually, and so it definitely is. I agree with you completely. I think antibody drug conjugates are really the way forward, because they're so much more tailored to the cancer than regular chemotherapy. The other drug, I think, that will be interesting to see in triple-negative breast cancer is trastuzumab-deruxtecan, which obviously is approved for HER2-positive breast cancer, but again, also has a bystander effect. And there's some data from one of the DESTINY studies basically showing activity in cancers that have low expression of HER2. So I think that's going to be very exciting. So I think there's a lot of exciting things happening in triple-negative breast cancer. There's a lot that I think we have to learn. I mean, biomarkers are going to be very important, particularly for immunotherapy. Do you have any other thoughts on other agents you're excited about in this setting? JACOB KETTLE: I'm always fascinated by precision oncology. And like you said, I haven't really found a lot of great targets for triple-negative breast cancer. It's tended to hold out its negativity. It doesn't have-- not as if we're finding a bunch of things. So I hold out hope, just that we come across a good marker, something else targetable for these folks. I share with you the enthusiasm about trastuzumab-deruxtecan, and how it might play a role in HER2 low. Interestingly enough, that's also a topoisomerase inhibitor type, very similar backbone, chemo-wise. But also just watching the IO story continue to play out, I think it was interesting just that breast cancer, really, especially the most common cancers, was really one of the last disease states to really see indications for immunotherapy. So just excited to see that story continue to unfold. And hopeful, always remain hopeful that we continue to push the needle forward, bit by bit, day by day. RUTH O'REGAN: I completely agree, and that was a great discussion. So that's all we have for today. I want to thank you, Dr. Kettle, for a great conversation. And thank you so much to all our listeners tuning into this episode of the ASCO Education Podcast. SPEAKER: Thank you for listening to this week's episode of the ASCO eLearning Weekly Podcast. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive e-learning center at elearning.asco.org.

In this episode, José Ignacio Nolazco, MD, and Alejandro Nolazco, MD, discuss in Spanish the latest immuno-oncology developments in the treatment of urothelial cancer from an Argentinian perspective.  Presenters:José Ignacio Nolazco, MD  Urology FollowHospital Universitario AustralBuenos Aires, ArgentinaAlejandro Nolazco, MDAssociate ProfessorDepartment of UrologyUniversidad Austral and Universidad Católica ArgentinaBuenos Aires, ArgentinaContent based on an online IME program supported by educational grants from EMD Serono, Inc and Pfizer.Link to full program, including associated downloadable slidesets and on-demand Webcast:https://bit.ly/3kJC5SL 

This episode covers cisplatin and carboplatin!

In this episode, Guiseppe Procopio, MD, and Cora N. Sternberg, MD, FACP, discuss in Italian the latest immuno-oncology developments in the treatment of urothelial cancer.  Presenters:Guiseppe Procopio, MD  Head of the Medical Oncology Genitourinary, Istituto Nazionale TumoriMedical OncologyFondazione IRCCS Istituto Nazionale dei TumoriMilan, ItalyCora N. Sternberg, MD, FACPProfessor of MedicineDepartment of Hematology/OncologyWeill Cornell MedicineNew York, New York, USAContent based on an online IME program supported by educational grants from EMD Serono, Inc and Pfizer.Link to full program, including associated downloadable slidesets and on-demand Webcast: http://bit.ly/3kJC5SL

Dr. Andreas Rimner of Memorial Sloan Kettering Cancer Center joins us to discuss a clinical trial "Testing the Addition of Targeted Radiation Therapy to Surgery and the Usual Chemotherapy Treatment (Pemetrexed and Cisplatin [or Carboplatin]) for Stage I-IIIA Malignant Pleural Mesothelioma." Dr. Rimner is a radiation oncologist specializing in thoracic cancers. He in interviewed by Mary Hesdorffer, expert nurse practitioner and executive director of the Mesothelioma Applied Research Foundation. Patients who need help with their diagnosis can contact Mary Hesdorffer, NP through the organization's website. The Mesothelioma Applied Research Foundation is the only national nonprofit organization dedicated to eradicating mesothelioma by providing patient services and education; funding peer-reviewed research; and advocating for government funding of mesothelioma research. More information about the organization is available at www.curemeso.org.

In this episode, Félix Guerrero Ramos, MD, PhD, FEBU, and Óscar Rodríguez-Faba, MD, discuss in Spanish the latest immuno-oncology developments in the treatment of urothelial cancer. Presenters:Félix Guerrero Ramos, MD, PhD, FEBU Teaching CollaboratorDepartment of SurgeryMedicine SchoolUniversidad Complutense de MadridAttending UrologistDepartment of UrologyUroOncology UnitMadrid, Spain Óscar Rodríguez-Faba, MD UrologistUro-OncologyFundació PuigvertBarcelona, Catalonia, SpainContent based on an online IME program supported by educational grants from EMD Serono, Inc and Pfizer.Link to full program, including associated downloadable slidesets and on-demand Webcast:http://bit.ly/3kJC5SL

In this episode, Alain Ravaud, MD, PhD, and Marine Gross-Goupil, MD, PhD, discuss in French the latest immuno-oncology developments in the treatment of urothelial cancer. Presenters:Alain Ravaud, MD, PhD Professor of Medical OncologyHead of Department of Medical OncologyBordeaux University HospitalBordeaux, FranceMarine Gross-Goupil, MD, PhD Medical OncologistSaint-André HospitalBordeaux University HospitalBordeaux, FranceContent based on an online IME program supported by educational grants from EMD Serono, Inc and Pfizer.Link to full program:https://bit.ly/3kJC5SL

Should patients with hypertension who are hospitalized due to COVID-19 continue to take angiotensin-converting enzyme inhibitors and angiotensin receptor blockers? Find out about this and more in today’s PV Roundup podcast.

We'll discuss the efficacy of a triplet combination therapy in BRCA-mutated, HER2-negative advanced breast cancer. Then, we'll move on to a report that detailed multiorgan immunotherapy-related adverse events in patients treated with atezolizumab. Last, we'll review the FDA's approval of the RET-targeted therapy pralsetinib in patients with metastatic RET fusion–positive non–small cell lung cancer.Coverage of stories discussed this week on ascopost.com:Addition of Veliparib to Carboplatin/Paclitaxel in Previously Treated Patients With BRCA-Mutated Advanced Breast Cancer: BROCADE3 TrialNew Study Focuses on Multiorgan Immunotherapy-Related Adverse Events in Clinical TrialsFDA Approves Pralsetinib for Metastatic RET Fusion–Positive NSCLCTo listen to more podcasts from ASCO, visit asco.org/podcasts.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.11.245969v1?rss=1 Authors: Szikriszt, B., Poti, A., Nemeth, E., Kanu, N., Swanton, C., Szuts, D. Abstract: Platinum-based drugs are a mainstay of cancer chemotherapy. However, their mutagenic effect can increase tumour heterogeneity, contribute to the evolution of treatment resistance, and also induce secondary malignancies. We coupled whole genome sequencing with phenotypic investigations on two cell line models to compare the magnitude and understand the mechanism of mutagenicity of cisplatin, carboplatin and oxaliplatin. Cisplatin induced significantly more base substitution mutations than carboplatin or oxaliplatin when used at equitoxic concentrations on human TK6 or chicken DT40 cells, and also induced the highest number of short insertions and deletions. Assessment through histone H2AX phosphorylation and single cell agarose gel electrophoresis suggested that cisplatin caused more DNA damage than carboplatin or oxaliplatin. The analysis of base substitution spectra revealed that all three tested platinum drugs elicit both a direct mutagenic effect at purine dinucleotides, and an indirect effect of accelerating endogenous mutagenic processes. Whereas the direct mutagenic effect correlated with the level of DNA damage caused, the indirect mutagenic effects were equal. The different mutagenicity and DNA damaging effect of equitoxic platinum drug treatments suggests that DNA damage independent mechanisms significantly contribute to their cytotoxicity. Thus, the comparatively high mutagenicity of cisplatin should be taken into account in the design of chemotherapeutic regimens. Copy rights belong to original authors. Visit the link for more info

ASCO's updated 2017 antiemetic guidelines recommend NK-1 antagonists to prevent CINV with standard Q 3 week carboplatin (i.e. AUC 5-6), but how good are the data to support that? We dive into the supporting data.

The basic must-know information for carboplatin, for students, residents, or anyone looking for a refresher.

In the first episode of Blood & Cancer, David Henry, MD (http://bit.ly/2MFDfzm), welcomes Richard J. Gralla, MD (http://bit.ly/2ShsxEv), or the Albert Einstein College of Medicine in New York. The topic today centers around antiemetics and ways to use them. And later, Ilana Yurkiewicz, MD (https://stanford.io/2RXPixR), debuts her segment Clinical Correlations all about hematology care. Visit MDedge/hematology-oncology  Show Notes By Emily Bryer, DO Highly emetic chemotherapy regimens include cisplatin, dacarbazine, anthracycline, and cyclophosphamide combinations Treatment should include an NK1 receptor antagonist, dexamethasone, and a 5HT3 antagonist All 5HT3 antagonists should be given only once (no evidence that prn or delayed administration is helpful) Olanzapine is an effective antiemetic, although its precise role and dose are undergoing investigation An all-oral regimen for highly emetic could include Netupitant (NK1) and palonosetron (long-acting 5HT3) (NEPA) + Oral Dex + Olanzapine Moderately emetic chemotherapy regimens include irinotecan and taxotere Treatment should include 5HT3 antagonist and dexamethasone Carboplatin causes more emesis than initially thought Improvement with NK1 antagonist yields a 15% decreased risk of emesis Guidelines now recommending NK1 with carboplatin Low emetic chemotherapy regimens include gemcitabine, pemetrexed as single agent Single drug: one dose of corticosteroid or one dose of 5HT3 antagonist Minimal emetic chemotherapy regimens include vincristine or bleomycin No drugs are recommended for acute or delayed nausea/emesis 20 mg Dexamethasone IV (or 12 mg PO 12 mg) should be administered only on day 1 of chemotherapy. Dexamethasone can be spared after that unless cisplatin (would require 2 days of steroids) Marijuana and THC have some antiemetic properties, but are about one quarter as effective as 5HT3 antagonists Lorazepam may be used in anticipatory emesis started a few days prior to chemotherapy References:  Ann Oncol. 2014 Jul;25(7):1333-9. JCSO 2015;13(4):128-30. JCSO 2016;4(1):11-20. Contact information: Contact us: podcasts@mdedge.com MDedge on Twitter: @mdedgehemonc Dr. Ilana Yurkiewicz on Twitter: @ilanayurkiewicz Dr. Yurkiewicz on MDedge: http://bit.ly/2DItTAb  

Dr Han presents results at the San Antonio Breast Cancer Symposium 2016 from a randomised phase II study of veliparib against placebo in combination with carboplatin and paclitaxel, for patients with locally recurrent of metastatic BRCA1/2 mutated breast cancer. The data presented at this press conference reflects two arms of a three arm study, with the veliparib plus temozolomide results not yet available. Dr Han describes the addition of veliparib as well tolerated, with similar toxicity profile to the placebo arm, and notes an improvement in partial r response rate, though clinical benefit and duration of response was equivalent to placebo.

Prof Minckwitz talks to ecancertv at SABCS 2015 about his research into adding carboplatin to presurgery chemotherapy. According to results from the randomised phase II GeparSixto clinical trial there was improved disease-free survival for patients with triple-negative breast cancer.

Dr. Jack West, Swedish Cancer Institute, discusses current trials seeking to determine the efficacy of combining immunotherapy agents in lung cancer.

Dr. Jack West, Swedish Cancer Institute, discusses current trials seeking to determine the efficacy of combining immunotherapy agents in lung cancer.

Dr. Jack West, Swedish Cancer Institute, discusses current trials seeking to determine the efficacy of combining immunotherapy agents in lung cancer.

Dr. Jack West, Swedish Cancer Institute, raises the question of whether to use immune checkpoint inhibitors as first-line treatment of lung cancer, alone or in combination with chemotherapy.

Dr. Jack West, Swedish Cancer Institute, raises the question of whether to use immune checkpoint inhibitors as first-line treatment of lung cancer, alone or in combination with chemotherapy.

Dr. Jack West, Swedish Cancer Institute, raises the question of whether to use immune checkpoint inhibitors as first-line treatment of lung cancer, alone or in combination with chemotherapy.

Dr. Jack West, Swedish Cancer Institute, defines maintenance therapy in advanced NSCLC and discusses maintenance treatment strategies.

Dr. Jack West, Swedish Cancer Institute, defines maintenance therapy in advanced NSCLC and discusses maintenance treatment strategies.

Dr. Jack West, Swedish Cancer Institute, defines maintenance therapy in advanced NSCLC and discusses maintenance treatment strategies.

Dr. Jack West, Swedish Cancer Institute, identifies the best choice for first-line chemotherapy for large-cell neuroendocrine histology.

Dr. Jack West, Swedish Cancer Institute, identifies the best choice for first-line chemotherapy for large-cell neuroendocrine histology.

Dr. Jack West, Swedish Cancer Institute, identifies the best choice for first-line chemotherapy for large-cell neuroendocrine histology.

Dr. Jack West, Swedish Cancer Institute, reviews the choices for a first-line chemotherapy regimen based on a squamous histology.

Dr. Jack West, Swedish Cancer Institute, reviews the choices for a first-line chemotherapy regimen based on a squamous histology.

Dr. Jack West, Swedish Cancer Institute, reviews the choices for a first-line chemotherapy regimen based on a squamous histology.

Dr. Jack West, Swedish Cancer Institute, addresses the issue of choosing a first-line chemotherapy regimen based on an adenocarcinoma histology.

Dr. Jack West, Swedish Cancer Institute, addresses the issue of choosing a first-line chemotherapy regimen based on an adenocarcinoma histology.

Dr. Jack West, Swedish Cancer Institute, addresses the issue of choosing a first-line chemotherapy regimen based on an adenocarcinoma histology.

Dr. Jack West, Swedish Cancer Institute, discusses the anti-angiogenic agent bevacizumab (Avastin) and the trial evidence of its efficacy for non-squamous NSCLC.

Dr. Jack West, Swedish Cancer Institute, discusses the anti-angiogenic agent bevacizumab (Avastin) and the trial evidence of its efficacy for non-squamous NSCLC.

Dr. Jack West, Swedish Cancer Institute, discusses the anti-angiogenic agent bevacizumab (Avastin) and the trial evidence of its efficacy for non-squamous NSCLC.

Dr. Jack West, Swedish Cancer Institute, identifies the platinum-based chemotherapy doublet as the backbone of first-line treatment for the majority of NSCLC patients.

Dr. Jack West, Swedish Cancer Institute, identifies the platinum-based chemotherapy doublet as the backbone of first-line treatment for the majority of NSCLC patients.

Dr. Jack West, Swedish Cancer Institute, identifies the platinum-based chemotherapy doublet as the backbone of first-line treatment for the majority of NSCLC patients.

Dr. Nasser Hanna, Indiana University Health, lists chemo regiments appropriate for use with radiation in locally advanced NSCLC.

Dr. Nasser Hanna, Indiana University Health, lists chemo regiments appropriate for use with radiation in locally advanced NSCLC.

Dr. Nasser Hanna, Indiana University Health, lists chemo regiments appropriate for use with radiation in locally advanced NSCLC.

Dr. Jared Weiss, UNC Lineberger Comprehensive Cancer Center, discusses the use of single agent vs. doublet chemotherapy in elderly patients.

Dr. Jared Weiss, UNC Lineberger Comprehensive Cancer Center, discusses the use of single agent vs. doublet chemotherapy in elderly patients.

Dr. Jared Weiss, UNC Lineberger Comprehensive Cancer Center, discusses the use of single agent vs. doublet chemotherapy in elderly patients.

Dr. David Spigel, Sarah Cannon Cancer Center, outlines treatment options for squamous lung cancer.

Dr. David Spigel, Sarah Cannon Cancer Center, outlines treatment options for squamous lung cancer.

Dr. David Spigel, Sarah Cannon Cancer Center, outlines treatment options for squamous lung cancer.

Dr. David Spigel, Sarah Cannon Cancer Center, outlines treatment options for squamous lung cancer.

Dr. David Spigel, Sarah Cannon Cancer Center, outlines treatment options for squamous lung cancer.

Dr. David Spigel, Sarah Cannon Cancer Center, outlines treatment options for squamous lung cancer.

Dr. Jared Weiss from the University of North Carolina, reviews several options as induction therapy for head and neck cancer and focuses on the potential appeal and tolerability of the combination of weekly carboplatin and paclitaxel with cetuximab.

Dr. Jared Weiss from the University of North Carolina, reviews several options as induction therapy for head and neck cancer and focuses on the potential appeal and tolerability of the combination of weekly carboplatin and paclitaxel with cetuximab.

Dr. Jared Weiss from the University of North Carolina, reviews several options as induction therapy for head and neck cancer and focuses on the potential appeal and tolerability of the combination of weekly carboplatin and paclitaxel with cetuximab.

Dr. Jared Weiss from the University of North Carolina, reviews several options as induction therapy for head and neck cancer and focuses on the potential appeal and tolerability of the combination of weekly carboplatin and paclitaxel with cetuximab.

Dr. Jared Weiss from the University of North Carolina, reviews several options as induction therapy for head and neck cancer and focuses on the potential appeal and tolerability of the combination of weekly carboplatin and paclitaxel with cetuximab.

Dr. Jared Weiss from the University of North Carolina, reviews several options as induction therapy for head and neck cancer and focuses on the potential appeal and tolerability of the combination of weekly carboplatin and paclitaxel with cetuximab.

Weichteilsarkome (STS) sind seltene maligne Neoplasien, die von bindegewebigen Strukturen wie Fett-, Muskel- oder Stützgewebe ausgehen und im gesamten Körper auftreten können. Goldstandard der Therapie ist die Resektion aller Manifestationen unter Mitnahme ausreichender Sicherheitsabstände. Da dies jedoch nicht in allen Patienten möglich ist, wird versucht, durch Verabreichung zytostatischer Substanzen eine Tumormassenreduktion zur erreichen. Dies gelingt mit den vorhandenen Chemotherapeutika mit erwiesener Wirksamkeit, insbesondere Doxorubicin, jedoch nur in etwa einem Drittel aller Patienten. Es konnte gezeigt werden, dass die Anwendung einer regionalen Hyperthermie (RHT) das Ansprechen der Patienten verbessert. Noch anspruchsvoller ist die Therapie von Patienten mit bereits metastasierter, rezidivierender oder Doxorubicin-refraktärer Erkrankung. Hier ist bislang keine Standardtherapie definiert. Die vorliegende Arbeit evaluiert eine in dieser Situation angewendete Polychemotherapie, bestehend aus Ifosfamid, Carboplatin und Etoposid (ICE) und appliziert in Kombination mit RHT, hinsichtlich ihrer Wirksamkeit und Verträglichkeit. Zudem wurde die Funktion natürlicher Killerzellen (NK-Zellen) als an der Kontrolle von Neoplasien beteiligte Effektoren des Immunsystems bei Patienten mit STS untersucht. Es konnte gezeigt werden, dass ICE + RHT eine wirksame Therapieoption für Patienten mit Anthrazyklin-refraktärem STS darstellt, und zwar sowohl für Patienten mit als auch ohne Fernmetastasen. Remissionen waren in 13% der Patienten nachweisbar, überwiegend konnte eine Krankheitsstabilisierung erreicht werden. Die Therapie ist jedoch assoziiert mit einer höhergradigen hämatologischen Toxizität und febrilen Komplikationen in einem signifikanten Anteil der Patienten, so dass ICE + RHT nur ausgewählten Patienten in gutem Allgemeinzustand verabreicht werden sollte. Die lytische Funktion der NK-Zellen war noch vor Beginn einer Therapie bei Patienten mit Erstdiagnose eines STS sowie bei Patienten mit Anthrazyklin- refraktärem STS signifikant reduziert im Vergleich zu gesunden Probanden. Während der Therapie mit ICE + RHT zeigte sich keine Zunahme dieser Funktion. Durch Inkubation der Zellen mit Interleukin 2 und TKD, einem Hitzeschockprotein- Derivat mit NK-stimulierenden Eigenschaften, konnte die Funktion in vitro wiederhergestellt werden. Die Augmentation der NK-Zell-Funktion könnte in Zukunft von therapeutischem Nutzen für Patienten mit STS sein.

Carboplatin-Gemcitabine-Bevacizumab represents an additional regimen to consider for management of recurrent platinum sensitive epithelial ovarian cancer, although it raises several questions regarding the role of bevacizumab in this disease setting.

Das Lungenkarzinom gehört in den Industrienationen zu den häufigsten Krebserkrankungen des Menschen. Als nachweislich gewichtigste Ursache für diesen Umstand steht der Zigarettenkonsum. Die Inzidenz der Neuerkrankungen nimmt bei den Frauen stetig zu, bei den Männern ist seit den 80igern ein leichter Abwärtstrend zu verzeichnen. Aufgrund der sehr unspezifischen Symptome beim Lungenkarzinom wird die Diagnose häufig erst sehr spät gestellt. Eine Operation kommt im fortgeschrittenen Stadium oft nicht mehr in Frage, weshalb die Therapie sich meist auf Radio- und Chemotherapie beschränkt. Obwohl die Therapie der vorliegenden Studie einen primär kurativen Ansatz hat, wird bei den meisten Patienten keine komplette Remission des Tumors erreicht und die Therapie bleibt palliativ beschränkt. Insbesondere in der Palliativmedizin gewinnt die Betrachtung der Lebensqualität der Patienten immer mehr an Beachtung. Wichtig sind nicht ausschließlich Überlebensraten und Toxizität sondern auch die subjektive Lebensqualität des Patienten. Der Patient als Individuum rückt in das Zentrum des Interesses. In der vorliegenden Dissertation wird die Lebensqualität im Verlauf von Patienten mit inoperablen NSCLC im Stadium IIIA und IIIB nach erhaltener Radiotherapie oder simultanen Radio- und Chemotherapie untersucht. Es handelt sich um eine prospektive multizentrische Phase III Studie. Die Studienpopulation setzt sich aus 303 Patienten zusammen. Zunächst erfolgte eine sechswöchige Induktions-Chemotherapie, die in zwei Zyklen mit Paclitaxel und Carboplatin durchgeführt wurde. Danach wurden die Patienten in zwei Behandlungsarme randomisiert, eine alleinige Radiotherapie oder eine simultanen Radio- und Chemotherapie, die ebenfalls sechs bis sieben Wochen andauerte. Die Lebensqualität wurde mittels dem Fragebogen QLQ-C30 von der EORTC aus Brüssel erfasst. Die Ergebnisse favorisieren die simultane Radio- und Chemotherapie. Es lässt sich ein signifikanter Unterschied der gesundheitsbezogenen Lebensqualität zwischen beiden Behandlungsarmen nach der Therapie feststellen. Die Patienten im Behandlungsarm der simultanen Radio- und Chemotherapie beurteilen ihre Lebensqualität im moderaten Maß besser als Patienten im Behandlungsarm der alleinigen Radiotherapie. Durch die simultane Radio- und Chemotherapie mit Paclitaxel kann die gesundheitsbezogene Lebensqualität der Patienten mit inoperablem nicht-kleinzelligen Lungenkarzinom im Stadium IIIA oder IIIB statistisch signifikant und klinisch relevant verbessert werden.

Background: Patients with metastatic breast cancer (MBC) are increasingly exposed to anthracyclines and taxanes either during treatment of primary breast cancer or during initial therapy of metastatic disease. The combination of gemcitabine and carboplatin was therefore investigated as an anthracycline- and taxane-free treatment option. Patients and Methods: MBC patients previously treated with chemotherapy were enrolled in a multicenter phase II study. Treatment consisted of gemcitabine (1,000 mg/m(2) i.v. on days 1 and 8) and carboplatin (AUC 4 i.v. on day 1) applied every 3 weeks. Results: Thirty-nine patients were recruited, and a total of 207 treatment cycles were applied with a median of 5 cycles per patient. One complete response and 11 partial responses were observed for an overall response rate of 31% (95% CI: 17-48%). Twelve patients (31%) had stable disease. Median time to progression was 5.3 months (95% CI: 2.6-6.7 months) and median overall survival from start of treatment was 13.2 months (95% CI: 8.7-16.7 months). Grade 3/4 hematological toxicity included leukopenia (59%/5%), thrombo-cytopenia (26%/23%) and anemia (10%/0%). Nonhematological toxicity was rarely severe. Conclusion: Combination chemotherapy with gemcitabine and carboplatin is an effective and generally well-tolerated treatment option for intensively pretreated patients with MBC. Due to a considerable incidence of severe thrombocytopenia it would be reasonable to consider starting gemcitabine at the lower dose level of 800 mg/m(2). Copyright (c) 2008 S. Karger AG, Basel.

Background: Prognosis of patients with metastatic soft tissue sarcomas (MSTS) is poor even after response to doxorubicin-based chemotherapy. We report phase II data of highdose chemotherapy and peripheral blood stem cell (PBSC) rescue in patients with MSTS responding to AI-G chemotherapy. Patients and Methods: From 1997 to 2002, 55 patients with MSTS were prospectively treated with 4 cycles of AI-G (doxorubicin 75 mg/m(2), ifosfamide 6 g/m(2) with G-CSF support). Responders received 2 further cycles of AI-G with collection of PBSCs. High-dose chemotherapy consisted of ifosfamide 12 g/m(2), carboplatin 1.2 g/m(2) and etoposide 1.2 g/m(2) (HD-ICE) followed by reinfusion of PBSCs. Results: Twenty-one of 55 patients (38%) were assessed as responders (3 complete response, 18 partial response). All but 2 patients refusing treatment received high-dose chemotherapy with PBSC rescue leading to grade IV hematologic toxicity without severe infections in all patients. No toxic death occurred. After a median follow-up time of 30 months, the median progression-free time was 12 months and survival time was 22 months for the entire group. By intent-totreat analysis the probability of 5-year progression-free survival was significantly higher for patients allocated to HD-ICE compared to patients receiving second-line chemotherapy after failure of AI-G (14 vs. 3%; p = 0.003). The estimated 5-year overall survival between the 2 groups was different (27% vs. not reached) but did not reach significance (p = 0.08). Conclusion: HD-ICE is feasible and promising in patients with chemosensitive MSTS. A randomized phase III trial is warranted to further define the role of HD-ICE as consolidation treatment in these patients.

Zusammenfassung: Unter den Tumoren des weiblichen Genitales hat das Ovarialkarzinom die schlechteste Prognose. Die Möglichkeiten der Früherkennung und apparativen Diagnostik sind sehr eingeschränkt so dass 75 % der Erkrankungen erst in den fortgeschrittenen FIGO-Stadien II, III und IV diagnostiziert werden. Es ist daher wichtig dass diese Frauen in spezialisierten Zentren durch onkologisch erfahrenen Gynäkologen behandelt werden. In unserer Klinik wurden in einem 5-Jahreszeitraum 118 Patientinnen zum Teil mehrmals sowohl operativ als auch chemotherapeutisch behandelt. Die Anzahl der Patientinnen die einheitlich behandelt wurde ist somit ausreichend groß um Aussagen über das operative und chemotherapeutische Vor-gehen treffen zu können. Die Ergebnisse zeigen das trotz ständiger Suche nach neuen Prognosefaktoren die bekannten Faktoren wie das Grading und der belassenen Tumorrest für das Überleben entscheidend sind. Der Tumormarker CA 125 liefert in dem Fall wenn er von den Tumorzellen expremiert wird ein gutes diagnostisches Instrument um das Ergebnis der Therapie und den Verlauf der Erkrankung zu kontrollieren. Die präoperative Diagnostik zeigte dass insbesondere über die sichere Dignität und das Ausmaß des Tumorbefalls keine sicheren Aussagen getroffen werden kann und eine optimale Vorbereitung der Patientinnen in jedem Ver-dachtsfall unerlässlich ist. In dieser Arbeit wurde ein Patientengut untersucht die in der First-Line The-rapie eine platinhaltige Chemotherapie und in der Second-Line Therapie eine Taxol Therapie nach einer möglichst maximalen tumorreduktiven Chirurgie erhielten. Die operativen Ergebnisse zeigen dass auch in fortgeschrittenen Tumorstadien bei vielen Patientinnen eine nahezu vollständige Tumorreduktion unter vertretbarer Morbidität möglich ist. Es ist uns unter Einsatz des CUSA-Gerätes gelungen eine geringe Quote an Darmresektionen zu erreichen so dass die notwendige Chemotherapie bei geringen postoperativen Komplikationen baldmöglichst begonnen werden konnte. Auch bei Frauen mit einem Rezidivtumor war durch die erneuten Operationen bei ca. der Hälfte der Pati-entinnen eine neuerliche Tumorfreiheit zu erzielen. Auch wenn diese Patientinnen in der Regel jünger und waren und eine bessere Prognose hatten zeigen unsere guten Überlebensraten nach 1. Interventionslaparotomie zwei weitere Ergebnisse. Erstens ist auch beim Rezidiv die maximal reduktive Tumorchirurgie möglich und sinnvoll und das Chemotherapeutikum Taxol hatte auch in der Second - Line Therapie gute Ansprechraten. Vergleicht man unsere Ergebnisse jedoch mit den neueren Daten seit Mitte der neunziger Jahre in dem Taxol und Carboplatin in der First-Line Therapie eingesetzt wurden können wir die verbesserten Überlebensraten nicht erreichen und haben aufgrund der vorliegenden Daten unser chemotherapeutisches Vorgehen seit 1994 umgestellt. Es scheint aufgrund dieser Daten eine erneute Diskussion um eine alleinige platinhaltige First-Line Therapie nicht sinnvoll. Wir denken das aufgrund unserer Ergebnisse bei der großen Anzahl der Patientinnen die unter gleichen Voraussetzungen behandelt wurden und der damit verbundenen Erfahrung es wichtig ist einen Vergleich zu unseren Patientinnen die nach Einführung des Taxol in die First-Line Therapie zu haben. Wir haben daher eine weitere Arbeit über einen gleichen Zeitraum mit Patientinnen unserer Klinik geplant und können dann sicher noch exaktere Aussagen über die Wertigkeit des operativen Vorgehens und der First-Line Chemotherapie treffen. Trotz des Wechsels des chemotherapeutischen Vorgehens sind die Überlebensraten dieser Erkrankung weiterhin ernüchternd und es muss weiterhin an einer verbesserten Früherkennung gearbeitet werden. Das unterschiedliche biologische Verhalten der heterogenen Gruppe der Ovarialtumore muss besser verstanden werden um eine optimale Chemotherapie im entsprechenden Stadium durchführen zu können. Die Möglichkeiten einer suffizienten Rezidivtherapie nach Einführung des Taxol und Carboplatin in die Primärtherapie müsste eindeutiger geklärt werden. Vielleicht können uns in Zukunft neue Ansätze im Bereich der molekularen Ebene innovative Diagnostiken und Therapien bringen und den Wunsch erfüllen das Ovarialkarzinom heilbar zu machen.

Das Ziel der vorliegenden Studie war es, Arbeitsbedingungen zu ermitteln, die einen Einfluss auf die Inkorporation von verarbeiteten Substanzen in der zentralen Zytostatikazubereitung in Krankenhäusern ausüben könnten. Anhand der Daten sollten Handlungsempfehlungen für eine Expositionsprophylaxe abgeleitet werden. In einer prospektiven Längsschnittstudie über drei Jahre sammelten 87 Apothekenmitarbeiter von 14 verschiedenen Kliniken bis zu 3 Mal fraktioniert 24 h Urin am Ende einer Arbeitswoche. Zusätzliche Proben wurden nach zwei Tagen sowie nach wenigstens drei Wochen Abwesenheit vom Arbeitsplatz gewonnen. Cyclophosphamid, Ifosfamid, Doxo-, Dauno-, Epi-, und Idarubicin sowie Platin (von den Medikamenten Cis- und Carboplatin) wurden mittels Gaschromatographie, Massenspektrometrie, HPLC und Voltammetrie bestimmt. Folgende Arbeitsbedingungen wurden per Fragebogen erhoben: Technische Ausstattung des Arbeitsplatzes, Reinigung des Arbeitsplatzes, Umgang mit den Primärverpackungen, Entsorgung des Zytostatika-Abfalls, die verarbeiteten Mengen an Zytostatika, sowie persönliche Schutzmaßnahmen (Material, Stärke und Tragedauer der Handschuhe). Die Ergebnisse beziehen sich im ersten Zyklus auf 87, im zweiten auf 81 und im dritten auf 69 Probanden. 64 % der Probanden hatten mindestens einen positiven Befund innerhalb der drei Zyklen (56 der ursprünglich 87 Probanden). 7 positive Befunde waren mit keiner dokumentierten Handhabung der Substanzen in Verbindung zu bringen. Es konnte gezeigt werden, dass Mitarbeiter, die Material anreichten, genauso betroffen waren, wie Mitarbeiter, die die Applikationen zubereiteten. Die Abfallaufbewahrung im Labor und die Anzahl der Zubereitungen waren signifikant mit der relativen Häufigkeit der positiven Befunde assoziiert. Die gehandhabte Menge und die Anzahl der Zubereitungen von Cyclophosphamid hatte einen signifikanten Einfluss auf einen positiven Befunden mit Cyclophosphamid. Es ist somit zu fordern, dass für Mitarbeiter, die Material anreichen, die gleichen Schutzvorschriften gelten wie für zubereitenden Personal. Weiterhin sollte die Möglichkeit für Schmierkontamination im Labor minimiert werd