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Dr. Allison Zibelli and Dr. Rebecca Shatsky discuss advances in breast cancer research that were presented at the 2025 ASCO Annual Meeting, including a potential new standard of care for HER2+ breast cancer, the future of ER+ breast cancer management, and innovations in triple negative breast cancer therapy. Transcript Dr. Allison Zibelli: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Allison Zibelli, your guest host of the podcast today. I'm an associate professor of medicine and a breast medical oncologist at the Sidney Kimmel Comprehensive Cancer Center at Jefferson Health. There was a substantial amount of exciting breast cancer data presented at the 2025 ASCO Annual Meeting, and I'm delighted to be joined by Dr. Rebecca Shatsky today to discuss some of these key advancements. Dr. Shatsky is an associate professor of medicine at UC San Diego and the head of breast medical oncology at the UC San Diego Health Moores Cancer Center, where she also serves as the director of the Breast Cancer Clinical Trials Program and the Inflammatory and Triple-Negative Breast Cancer Program.  Our full disclosures are available in the transcript of this episode. Dr. Shatsky, it's great to have you on the podcast today. Dr. Rebecca Shatsky: Thanks, Dr. Zibelli. It's wonderful to be here. Dr. Allison Zibelli: So, we're starting with DESTINY-Breast09, which was trastuzumab deruxtecan and pertuzumab versus our more standard regimen of taxane, trastuzumab pertuzumab for first-line treatment of metastatic HER2-positive breast cancer. Could you tell us a little bit about the study? Dr. Rebecca Shatsky: Yeah, absolutely. So, this was a long-awaited study. When T-DXd, or trastuzumab deruxtecan, really hit the market, a lot of these DESTINY-Breast trials were started around the same time. Now, this was a global, randomized, phase 3 study presented by Dr. Sara Tolaney from the Dana-Farber Cancer Institute of Harvard in Boston. It was assessing essentially T-DXd in the first-line setting for metastatic HER2-positive breast cancer in addition to pertuzumab. And that was randomized against our standard-of-care regimen, which was established over a decade ago by the CLEOPATRA trial, and we've all been using that internationally for at least the past 10 years. So, this was a large trial, and it was one-to-one-to-one of patients getting T-DXd plus pertuzumab, T-DXd alone, or THP, which mostly is used as docetaxel and trastuzumab and pertuzumab every three weeks for six cycles. And this was in over 1,000 patients; it was 1,159 patients with metastatic HER2-positive breast cancer. This was a very interesting trial. It was looking at the use of trastuzumab deruxtecan, but patients were started on this treatment for their first-line metastatic HER2-positive breast cancer with no end date to their T-DXd. So, it was, you know, you were started on T-DXd every 3 weeks until progression. Now, CLEOPATRA is a little bit different than that, though, as we know. So, CLEOPATRA has a taxane plus trastuzumab and pertuzumab. But generally, patients drop the taxane after about six to seven cycles because, as we know, you can't be really on a taxane indefinitely. You get pretty substantial neuropathy as well as cytopenias, other things that end up happening. And so, in general, that regimen has sort of a limited time course for its chemotherapy portion, and the patients maintained after the taxane is dropped on their trastuzumab and their pertuzumab, plus or minus endocrine therapy if the investigator so desires. And the primary endpoint of the trial was progression-free survival by blinded, independent central review (BICR) in the intent-to-treat population. And then it had its other endpoints as overall survival, investigator-assessed progression-free survival, objective response rates, and duration of response, and of course, safety. As far as the results of this trial, so, I think that most of us key opinion leaders in breast oncology were expecting that this was going to be a positive trial. And it surely was. I mean, this is a really, really active drug, especially in HER2-positive disease, of course. So, the DESTINY-Breast03 data really established that, that this is a very effective treatment in HER2-positive metastatic breast cancer. And this trial really, again, showed that. So, there were 383 patients that ended up on the trastuzumab plus deruxtecan plus pertuzumab arm, and 387 got THP, the CLEOPATRA regimen. What was really interesting also to note of this before I go on to the results was that 52% of patients on this trial had de novo metastatic disease. And that's pretty unusual for any kind of metastatic breast cancer trial. It kind of shows you, though, just how aggressive this disease is, that a lot of patients, they present with de novo metastatic disease. It's also reflecting the global nature of this trial where maybe the screening efforts are a little bit less than maybe in the United States, and more patients are presenting as later stage because to have a metastatic breast cancer trial in the United States with 52% de novo metastatic disease doesn't usually happen. But regardless, the disease characteristics were pretty well matched between the two groups. 54% of the patients were triple positive, or you could say hormone-positive because whether they were PR positive or ER positive and PR negative doesn't really matter in this disease. And so, the interim data cutoff was February of this year, of 2025. So, the follow-up so far has been about 29 months, so the data is still really immature, only 38% mature for progression-free survival interim analysis. But what we saw is that T-DXd plus pertuzumab, it really improved progression-free survival. It had a hazard ratio that was pretty phenomenal at 0.56 with a confidence interval that was pretty narrow of 0.44 to 0.71. So, very highly statistically significant data here. The progression-free survival was consistent across all subgroups. Overall survival, very much immature at this time, but of course, the trend is towards an overall survival benefit for the T-DXd group. The median durable response with T-DXd plus pertuzumab exceeded 3 years. Now, importantly, though, I want to stress this, is grade 3 or above treatment-emergent adverse events occurred in both subgroups pretty equally. But there were 2 deaths in the T-DXd group due to interstitial lung disease. And there was a 12.1% adjudicated drug-induced interstitial lung disease/pneumonitis event rate in the T-DXd group and only 1%, and it was grade 1-2, in the THP group. So, that's really the caveat of this therapy, is we know that a percentage of patients are going to get interstitial lung disease, and that some may have very serious adverse events from it. So, that's always something I keep in the back of my mind when I treat patients with T-DXd. And so, overall, the conclusions of the trial were pretty much a slam dunk. T-DXd plus pertuzumab, it had a highly statistically significant and clinically meaningful improvement in progression-free survival versus the CLEOPATRA regimen. And that was across all subgroups for first-line metastatic HER2-positive breast cancer here. And so, yeah, the data was pretty impressive. Just to go into the overall response rate, because that's always super important as well, you had 85.1% of patients having a confirmed overall RECIST response rate in the T-DXd plus pertuzumab group and a 78.6 in the CLEOPATRA group. The complete CR rate, complete response was 15.1% in the T-DXd group and 8.5 in the CLEOPATRA regimen. And it was really an effective regimen in this group, of course. Dr. Allison Zibelli: So, the investigators say at the end of their abstract that this is the new standard of care. Would you agree with that statement? Dr. Rebecca Shatsky: Yeah, that was a bold statement to make because I would say in the United States, not necessarily at the moment because the quality of life here, you have to think really hard about. Because one thing that's really important about the DESTINY-Breast09 data is that this was very much an international trial, and in many of the countries where patients enrolled on this, they were not able to access T-DXd off trial. And so, for them, this means T-DXd now or potentially never. And so, that is a really big difference whereas internationally, that may mean standard of care. However, in the US, patients have no issues accessing T-DXd in the second- or third-line settings. And right now, it's the standard of care in the second line in the United States, with all patients basically getting this second-line therapy except for some unique patients where they may be doing a PATINA trial regimen, which we saw at San Antonio Breast Cancer in 2024 of the triple-positive patients getting hormonal therapy plus palbociclib, which had a really great durable response. That was super impressive as well. Or there is the patient that the investigator can pick KADCYLA because the patient really wants to preserve their hair or maybe it's more indolent disease. But the quality of life on T-DXd indefinitely in the first-line setting is a big deal because, again, that CLEOPATRA regimen allows patients to drop their chemotherapy component about five to six months in. And with this, you're on a drug that feels very chemo-heavy indefinitely. And so, I think there's a lot more to investigate as far as what we're going to do with this data in the United States because it's a lot to commit a patient in the first-line metastatic setting. These de novo metastatic patients, some of them may be cured, honestly, on the HER2-targeting regimen. That's something we see these days. Dr. Allison Zibelli: So, very interesting trial. I'm sure we'll be talking about this for a long time.  So, let's move on to SERENA-6, which was, I thought, a very interesting trial. This trial took patients with ER positive, advanced breast cancer after six months on an AI (aromatase inhibitor) and a CDK4/6 inhibitor. They did ctDNA every two to three months, and when they saw an ESR1 mutation emerge, they changed half of the patients to camizestrant plus CDK4/6 and kept the other half on the AI plus CDK4/6. Can you talk about that trial a little bit, please? Dr. Rebecca Shatsky: Yeah, so this was a big trial at ASCO25. This was presented as a Plenary Session. So, this was camizestrant plus a CDK4/6 inhibitor, and it could have been any of the three, so palbo, ribo, or abemaciclib in the first-line metastatic hormone-positive population, and patients were on an AI with that. They were, interestingly, tested by ctDNA at baseline to see if they had an ESR1 mutation. So, that was an interesting feature of this trial. But patients had to have already been on their CDK4/6 inhibitor plus AI for at least 6 months to enroll. And then, as you mentioned, they got ctDNA testing every 2 to 3 months. This was also a phase 3, double-blind, international trial. And I do want to highlight again, international here, because that's important when we're considering some of this data in the U.S. because it influences some of the results. So, this was presented by Dr. Nick Turner of the Royal Marsden in the UK. So, just a little bit of background for our listeners on ESR1 mutations and why they're important. This is the most common, basically, acquired resistance mutation to patients being treated with aromatase inhibitors. We know that treatment with aromatase inhibitors can induce this. It makes a conformational change in the estrogen receptor that makes the estrogen receptor constitutively active, which allows the cell to signal despite the influence of the aromatase inhibitor to decrease the estrogen production so that the ligand binding doesn't matter as much as far as the cell signaling and transcription is concerned. And camizestrant, you know, as an oral SERD, just to explain that a little bit too; these are estrogen receptor degraders. The first-in-class of a selective estrogen receptor degrader to make it to market was fulvestrant. And that's really been our standard-of-care estrogen degrader for the past 25 years, almost 25 years. And so, a lot of us are just looking for some of these oral SERDs to replace that. But regardless, they do tend to work in the ESR1-mutated population. And we know that patients on aromatase inhibitors, the estimates of patients developing an ESR1 mutation, depending on which study you look at, somewhere between 30% to 50% overall, patients will develop this mutation with hormone-positive metastatic breast cancer. There is a small percentage of patients that have these at baseline without even treatment of an aromatase inhibitor. The estimates of that are somewhere between 0.5 and up to 5%, depending on the trial you look at and the population. But regardless, there is a chance someone on their CDK4/6 inhibitor plus AI at 6 months' time course could have had an ESR1 mutation at that time. But anyway, so they got this ctDNA every 2 to 3 months, and once they were found to develop an ESR1 mutation, the patients were then switched to the oral SERD. AstraZeneca's version of the oral SERD is camizestrant, 75 mg daily. And then their type of CDK4/6 inhibitor was maintained, so they didn't switch the brand of their CDK4/6 inhibitor, importantly. And that was looked at then for progression-free survival, but these were patients with measurable disease by RECIST version 1.1. And the data cut off here was November of 2024. This was a big trial, you know, and I think that that's influential here because this was 3,256 patients, and that's a lot of patients. So, they were all eligible. And then 315 patients ended up being randomized to switch to camizestrant upon presence of that ESR1 mutation. So, that was 157 patients. And then the other half, so they were randomized 1:1, they continued on their AI without switching to an oral SERD. That was 158 patients. They were matched pretty well. And so, their baseline characteristics, you know, the two subgroups was good. But this was highly statistically significant data. I'm not going to diminish that in any way. Your hazard ratio was 0.44. Highly statistically significant confidence intervals. And you had a median progression-free survival in those that switched to camizestrant of 16 months, and then the non-switchers was 9.2 months. So, the progression-free survival benefit there was also consistent across the subgroups. And so, you had at 12 months, the PFS rate was 60.7% for the non-treatment group and 33.4% in the treatment group. What's interesting, though, is we don't have overall survival data. This is really immature, only 12% mature as far as overall survival. And again, because this was an international trial and patients in other countries right now do not have the access to oral SERDs that the United States does, the crossover rate, they were not allowed to crossover, and so, a very few patients, when we look at progression-free survival 2 and ultimately overall survival, were able to access an oral SERD in the off-trial here and in the non-treatment group. And so, that's really important as far as we look at these results. Adverse events were pretty minimal. These are very safe drugs, camizestrant and all the other oral SERDs. They have some mild toxicities. Camizestrant is known for something weird, which is called photopsia, which is some flashing lights in the periphery of the eye, but it doesn't seem to have any serious clinical significance that we know of. It has a little bit of bradycardia, but it's otherwise really well tolerated. You know, I hate to say that because that's very subjective, right? I'm not the one taking the drug. But it doesn't have any serious adverse events that would cause discontinuation. And that's really what we saw in the trial. The discontinuation rates were really low. But overall, I mean, this was a positive trial. SERENA-6 showed that switching to camizestrant at the first sign of an ESR1 mutation on CDK4/6 inhibitor plus AI improved progression-free survival. That's all we can really say from it right now. Dr. Allison Zibelli: So, let's move on to ASCENT-04, which was a bit more straightforward. Sacituzumab govitecan plus pembrolizumab versus chemotherapy plus pembrolizumab in PD-L1-positive, triple-negative breast cancer. Could you talk about that study? Dr. Rebecca Shatsky: Yeah, so this was also presented by the lovely Sara Tolaney from Dana-Farber. And this study made me really excited. And maybe that's because I'm a triple-negative breast cancer person. I mean, not to say that I don't treat hundreds of patients with hormone- positive, but our unmet needs in triple negative are huge because this is a disease where you have got to throw your best available therapy at it as soon as you can to improve survival because survival is so poor in this disease. The average survival with metastatic triple-negative breast cancer in the United States is still 13-18 months, and that's terrible. And so, for full disclosure, I did have this trial open at my site. I was one of the site PIs. I'm not the global PI of the study, obviously. So, what this study was was for patients who had had at least a progression-free survival of 6 months after their curative intent therapy or de novo metastatic disease. They were PD-L1 positive as assessed by the Dako 22C3 assay of greater than or equal to a CPS score of 10. So, that's what the KEYNOTE-355 trial was based on as well. So, standard definition of PD-L1 positive in breast cancer here. And basically, these patients were randomized 1:1 to either their sacituzumab govitecan plus pembrolizumab, day 1 they got both therapies, and then day 8 just the saci, as is standard for sacituzumab. And then the other group got the KEYNOTE-355 regimen. So, that is pembrolizumab with – your options are carbogem there, paclitaxel or nab-paclitaxel. And it's up to investigator's decision which upon those they decided. They followed these patients for disease progression or unacceptable toxicity. It was really an impressive trial in my opinion because we know already that this didn't just improve progression-free survival, because survival is so poor in this disease, of course, we know that it improved overall survival. It's trending towards that very much, and I think that's going to be shown immediately. And then the objective response rates were better, which is key in this disease because in the first-line setting, you've got a lot of people who, especially your relapsed TNBC that don't respond to anything. And you lose a ton of patients even in the first-line setting in this disease. And so, this was 222 patients to chemotherapy and pembro and 221 to sacituzumab plus pembro. Median follow-up has only been 14 months, so it's still super early here. Hazard ratio so far of progression-free survival is 0.65, highly statistically significant, narrow confidence intervals. And so, the median duration of response here for the saci group was 16.5 months versus 9.2 months. So, you're getting a 7-month progression-free survival benefit here, which in triple negative is pretty fantastic. I mean, this reminds me of when we saw the ASCENT data originally come out for sacituzumab, and we were all just so happy that we had this tool now that doubled progression-free and overall survival and made such a difference in this really horrible disease where patients do poorly. So, OS is technically immature here, but it's really trending very heavily towards improvement in overall survival. Importantly, the treatment-related adverse events in this, I mean, we know sacituzumab causes neutropenia, people who are experienced with this drug know how to manage it at this point. There wasn't any really unexpected treatment-related adverse events. You get some people with sacituzumab who have diarrhea. It's usually pretty manageable with some Imodium. So, it was cytopenias predominantly in this disease in this population that were highlighted as far as adverse events. But I'm going to be honest, like I was surprised that this wasn't the plenary over the SERENA-6 data because this, in my mind, there we have a practice-changing trial. I will immediately be trying to use this in my PD-L1 population because, to be honest, as a triple-negative breast cancer clinical specialist, when I get a patient with metastatic triple-negative breast cancer who's PD-L1 positive, I think, "Oh, thank God," because we know that part of the disease just does better in general. But now I have something that really could give them a durable response for much longer than I ever thought possible when I started really heavily treating this disease. And so, this was immediately practice-changing for me. Dr. Allison Zibelli: I think that it's pretty clear that this is at least an option, if not the option, for this group of patients. Dr. Rebecca Shatsky: Yeah, the duration of responses here was – it's just really important because, I mean, I do think this will make people live longer. Dr. Allison Zibelli: So, moving on to the final study that we're going to discuss today, neoCARHP (LBA500), which was neoadjuvant taxane plus trastuzumab, pertuzumab, plus or minus carbo(platin) in HER2-positive early breast cancer. I think this is a study a lot of us have been waiting for. What was the design and the results of this trial? Dr. Rebecca Shatsky: I was really excited about this as well because I'm one of those people that was waiting for this. This is a Chinese trial, so that is something to take note of. It wasn't an international trial, but it was a de-escalation trial which had become really popular in HER2-positive therapy because we know that we're overtreating HER2-positive breast cancer in a lot of patients. A lot of patients we're throwing the kitchen sink at it when maybe that is not necessary, and we can really de-escalate and try to personalize therapy a little bit better because these patients tend to do well. So, the standard of care, of course, in HER2-positive curative intent breast cancer with tumors that are greater than 2 cm is to give them the TCHP regimen, which is docetaxel, carboplatin, trastuzumab, and pertuzumab. And that was sort of established by several trials in the NeoSphere trial, and now it's been repeated in a lot of different studies as well. And so, that's really the standard of care that most people in the United States use for HER2-positive curative intent breast cancer. This was a trial to de-escalate the carboplatin, which I was super excited about because many of us who treat this disease a lot think carbo is the least important part of the therapy you're giving there. We don't really know that it's necessary. We've just been doing it for a long time, and we know that it adds a significant amount of toxicity. It causes thrombocytopenia, it causes severe nausea, really bad cytopenias that can be difficult in the last few cycles of this to manage. So, this trial was created. It randomized patients one to one with stage 2 and 3 HER2-positive breast cancer to either get THP, a taxane, pertuzumab, trastuzumab, similar to the what we do in first-line metastatic HER2-positive versus the whole TCHP with a carboplatin AUC of 6, which is what's pretty standard. And it was a non-inferiority trial, so important there. It wasn't to establish superiority of this regimen, which none of us, I think, were looking for it to. And it was a modified intent-to-treat population. And so, all patients got at least one cycle of this to be assessed as a standard for an intent-to-treat trial. And so, they assumed a pCR rate of about 62.8% for both groups. And, of course, it included both HER2-positive triple positives and ER negatives, which are, you know, a bit different diseases, to be honest, but we all kind of categorize them and treat them the same. And so, this trial was powered appropriately to detect a non-inferiority difference. And so, we had about 380 patients treated on both arms, and there was an absolute difference of only 1.8% of those treated with carbo versus those without. Which was fantastic because you really realized that de-escalation here may be something we can really do. And so, the patients who got, of course, the taxane regimen had fewer adverse events. They had way fewer grade 3 and 4 adverse events than the THP group. No treatment-associated deaths occur, which is pretty standard for- this is a pretty safe regimen, but it causes a lot of hospitalizations due to diarrhea, due to cytopenias, and neutropenic fever, of course. And so, I thought that this was something that I could potentially enact, you know, and be practice-changing. It's hard to say that when it's a trial that was only done in China, so it's not necessarily the United States population always. But I think for patients moving forward, especially those with, say, a 2.5 cm tumor, you know, node negative, those, I'd feel pretty comfortable not giving them the carboplatin here. Notes that I want to make about this population is that the majority were stage 2 and not stage 3. They weren't necessarily your inflammatory HER2-positive breast cancer patients. And that the taxane that was utilized in the trial is a little different than what we use in the United States. The patients were allowed to get nab-paclitaxel, which we don't have FDA approval for in the first-line curative intent setting for HER2-positive breast cancer in the United States. So, a lot of them got abraxane, and then they also got paclitaxel. We tend to use docetaxel every 3 weeks in the United States. So, just to point out that difference. We don't really know if that's important or not, but it's just a little bit different to the population we standardly treat. Dr. Allison Zibelli: So, are there patients that you would still give TCHP to? Dr. Rebecca Shatsky: Yeah, great question. I've been asked that a lot in the past like week since ASCO. I'd say in my inflammatory breast cancer patients, that's a group I do tend to sometimes throw the kitchen sink at. Now, I don't actually use AC in those because I know that that was the concern, but I think the TRAIN-2 trial really showed us you don't need to use Adriamycin in HER2-positive disease unless it's like refractory. So, I don't know that I would throw this on my stage 3C or inflammatory breast cancer patients yet because the majority of this were not stage 3. So, in your really highly lymph node positive patients, I'm a little bit hesitant to de-escalate them from the start. This is more of a like, if there's serious toxicity concerns, dropping carbo is absolutely fine here. Dr. Allison Zibelli: All right, great.  Thank you, Dr. Shatsky, for sharing your valuable insights with us on the ASCO Daily News Podcast today. Dr. Rebecca Shatsky: Thanks so much, Dr. Zibelli and ASCO Daily News. I really want to thank you for inviting me to talk about this today. It was really fun, and I hope you find my opinions on some of this valuable. And so, I just want to thank everybody and my listeners as well. Dr. Allison Zibelli: And thank you to our listeners for joining us today. You'll find the links to all the abstracts discussed today in the transcript of this episode. Finally, if you like this podcast and you learn things from it, please take a moment to rate, review, and describe because it helps other people find us wherever you get your podcasts. Thank you again. Disclaimer: 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. More on today's speakers Dr. Allison Zibelli Dr. Rebecca Shatsky @Dr_RShatsky Follow ASCO on social media:  @ASCO on Twitter  @ASCO on Bluesky  ASCO on Facebook  ASCO on LinkedIn   Disclosures: Dr. Allison Zibelli: No relationships to disclose Dr. Rebecca Shatsky: Consulting or Advisory Role: Stemline, Astra Zeneca, Endeavor BioMedicines, Lilly, Novartis, TEMPUS, Guardant Health, Daiichi Sankyo/Astra Zeneca, Pfizer Research Funding (Inst.): OBI Pharma, Astra Zeneca, Greenwich LifeSciences, Briacell, Gilead, OnKure, QuantumLeap Health, Stemline Therapeutics, Regor Therapeutics, Greenwich LifeSciences, Alterome Therapeutics  

La Cofepris emitió una alerta por la falsificación de medicamentos de Kadcyla, Stribild, Anesket Detienen a 4 implicados en el asesinado del exalcalde de IxtapalucaRealizan con éxito trasplante simultaneo de Bomba cardíaca y riñón de cerdo en EEUUMás información en nuestro podcast

In a recent conversation with CancerNetwork®, Sara A. Hurvitz, MD, FACP, senior vice president and director of the Clinical Research Division at Fred Hutch Cancer Center and head of the Division of Hematology and Oncology at the University of Washington Department of Medicine, discussed new treatment options for patients with metastatic HER2-positive breast cancer.  In the discussion, Hurvitz highlighted findings from the phase 3 HER2CLIMB-02 trial (NCT03975647), which assessed the efficacy and safety of tucatinib (Tukysa) plus ado-trastuzumab emtansine (Kadcyla; T-DM1) in patients with HER2-positive breast cancer, specifically those with brain metastases.  Patients enrolled in this trial experienced a significant improvement in progression-free survival (PFS) with the tucatinib-based regimen. Data presented at the 2023 San Antonio Breast Cancer Symposium (SABCS) highlighted that the median time to disease progression or death was 9.5 months (95% CI, 7.4-10.9) and 7.4 months (95% CI, 5.6-8.1 in the experimental arm and placebo arm, respectively (HR, 0.76; 95% CI, 0.61-0.95; P = .0163). In patients with brain metastases, the median time to disease progression or death was 7.8 months (95% CI, 6.7-10.0) and 5.7 months (95% CI, 4.6-7.5) in the experimental arm and placebo arm, respectively (HR, 0.64; 95% CI, 0.46-0.89). Investigators reported that toxicity in the experimental arm was generally manageable and reversible. “This was a study that only enrolled patients who were naive to trastuzumab deruxtecan [T-DXd; Enhertu],” Huvitz said. “We know that T-DXd has substantial improvements in PFS and survival, so having so many patients receive this [agent] after progression is certainly going to impact our ability to observe survival differences. About 15% of patients in each arm also went on to receive tucatinib. These are pretty exciting results for our patients, especially those with brain metastases. This study did enroll, as I said, patients with brain metastases, who comprised 44% or so of the entire population enrolled in this study. These are interesting data, and we'll see if this regimen is ultimately approved.” Reference Hurvitz SA, Loi S, O'Shaughnessy J, et al. HER2CLIMB-02: randomized, double-blind phase 3 trial of tucatinib and trastuzumab emtansine for previously treated HER2-positive metastatic breast cancer. Presented at the 2023 San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, TX. Session GS01-10.

The last week was a busy one for us here at CURE® and across the oncology space in general. There were two major meetings we covered: the San Antonio Breast Cancer Symposium and the American Society of Hematology Annual Meeting.  The San Antonio Breast Cancer Symposium — also known as SABCS — features breast cancer research conducted around the globe. We had editors on the ground in San Antonio, as well as back in our office covering the meeting. Here are some highlights from SABCS.  And, to view all of our conference coverage, be sure to check out curetoday.com/conference Kadcyla Is the ‘First Therapy to Show Improved Survival' in a Breast Cancer Subset For in patients with HER2-positive early breast cancer that still had remaining invasive disease after undergoing neoadjuvant therapy Kadcyla outperformed Herceptin when it came to overall survival, which is the time until death of any cause, and invasive disease-free survival, which is the time patients live without experience metastases or invasive disease.  The findings, which come out of the KATHERINE trial, mark the “first therapy to show an improved survival after post-surgical therapy in patients with HER2-positive early breast cancer and residual invasive disease after neoadjuvant therapy,” according to study author, Dr. Sibylle Loibl, who presented the findings at SABCS.  More specifically, at the 8.4-year follow-up mark, 70.1% of patients in the Kadcyla group and 62% in the Herceptin group were still alive. Also at that point, 32.2% given Kadcyla did not develop invasive disease, compared with 19.7% of patients in the Herceptin group.  Keytruda, Chemo Show Early-Stage Breast Cancer Event-Free Survival Benefits Findings from phase 3 KEYNOTE-522 trial showed that presurgical Keytruda plus chemotherapy, followed by postsurgical Keytruda led to improved event-free survival — that's time a patient lives without complications from their disease — in patients with high-risk, early-stage triple-negative breast cancer.  At a median follow-up of 63.1 months, the five-year event-free survival rate was 81.3% with neoadjuvant Keytruda/chemotherapy followed by adjuvant Keytruda compared with 72.3% in those who received placebo/chemotherapy and then placebo. These findings, according to Dr. Peter Schmid, further support the use of this Keytruda regimen as the standard of care for this patient population.  Tecentriq Plus Perjeta, Herceptin, Chemo Does Not Improve pCR in HER2+ Breast Cancer Another phase 3 trial — the APTneo Michelangelo — showed that adding Tecentriq and Herceptin to Perjeta and chemotherapy actually did not lead to a statistically significant improvement in pathologic complete response (that's the disappearance of cancer) when given in the presurgical setting for patients with HER2-positive breast cancer.  The study found that while Tecentriq and Herceptin-containing regimens did lead to a higher number of pathologic complete responses, these difference between the two treatment groups was not statistically significant, meaning that the researchers could not definitively say that one therapy was the result of better outcomes.  No Racial Difference in Recurrence-Free Survival in HR+, HER2- Breast Cancer While research has shown that Black and White patients with HR-positive, HER2-negative breast cancer tend to have different survival outcomes, research presented at SABCS found that three-year recurrence-free survival is actually comparable between the two groups.   “More aggressive treatment can improve outcomes for (patients with HR-positive, basal-type tumors), as demonstrated by improved (overall survival) in (those who) achieved pathologic complete response,” study investigators stated in the poster. “These data highlight the importance of genomic testing to help optimize treatment and reduce outcome disparities in Black women.”

You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world's leading professional organization for doctors who care for people with cancer. 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses. In this podcast, Cancer.Net Associate Editor Dr. Norah Lynn Henry covers new research in breast cancer treatment, prevention, and survivorship presented at the 2022 San Antonio Breast Cancer Symposium, held December 6-10. Dr. Henry is a Professor and Interim Chief of the University of Michigan's Division of Hematology/Oncology in the Department of Internal Medicine and is the Breast Oncology Disease Lead at the Rogel Cancer Center in Ann Arbor, Michigan. View Dr. Henry's disclosures at Cancer.Net. Dr. Henry: Hi, I'm Dr. Lynn Henry, a breast cancer oncologist from the University of Michigan Rogel Cancer Center. Welcome to this quick summary of updates from the 2022 San Antonio Breast Cancer Symposium. I have no conflicts of interest for any of the trials that I will talk about today. First, I'm going to give a very brief overview of the types of breast cancer, and then talk about some research that was presented on both metastatic and early-stage breast cancer. As a reminder, there are multiple kinds of breast cancer. Some breast cancers are called hormone receptor-positive or estrogen receptor-positive and are stimulated to grow by the hormone estrogen. We treat those cancers with anti-estrogen treatments, which block estrogen or lower estrogen levels. We often combine anti-estrogen treatments with other medications to try to make them work even better against the cancer. Other breast cancers are called HER2-positive. These are often more aggressive cancers, but because they have extra copies of HER2, they often respond to treatments that block HER2. Finally, there are breast cancers that don't have hormone receptors or HER2 receptors. These are called triple-negative breast cancer and are also often fairly aggressive cancers. One of the most exciting takeaways from the San Antonio meeting was the promise of new medications on the horizon to treat hormone receptor-positive, HER2-negative metastatic breast cancer. A commonly used treatment for metastatic breast cancer that is hormone receptor-positive and HER2-negative is fulvestrant, which is a type of medicine called “SERD,” or selective estrogen receptor degrader. At the meeting, we heard new data about 2 new SERD medications: elacestrant that was tested in the EMERALD trial and camizestrant that was tested in the SERENA trial, both of which are oral pills instead of injection medications and both of which may work particularly well against tumors that have mutations in the estrogen receptor called ESR1. In addition, we heard about capivasertib, which is an AKT inhibitor that was shown to work well when combined with fulvestrant and had less toxicity than some of the similar drugs that had previously been tested. For treatment of HER2-positive metastatic breast cancer, there are now a lot of medications that have been FDA approved, so some of the questions that clinical trials are now examining are related to what order we should use the medications in when we are treating patients. We heard about 2 studies of the medication trastuzumab deruxtecan, which I'm going to refer to as Enhertu. This drug is a combination of the anti-HER2 antibody trastuzumab plus a chemotherapy drug, and the antibody targets the drug to a cancer like a guided missile. Enhertu is currently routinely used to treat patients with metastatic HER2-positive breast cancer. We heard updated data that showed that when Enhertu was compared head-to-head against trastuzumab emtansine, also known as Kadcyla, patients who were treated with Enhertu were able to stay on the medication for a lot longer compared to patients who were treated with Kadcyla. We also heard that for patients who had already been treated with Kadcyla but it was no longer working, it is reasonable to switch to treatment with Enhertu at that point, because it is still likely to be effective. These studies may help oncologists decide what order to use these newer medications when treating patients with HER2-positive breast cancer. To switch gears a little bit, I'll now talk about another study I found interesting. This one is in the setting of people who are at high risk of developing breast cancer, but who haven't actually been diagnosed with cancer yet. In general, people are recommended to take either tamoxifen or an aromatase inhibitor medication, which is the same as treatment for patients who have been diagnosed with hormone receptor-positive breast cancer. But in this case, it's trying to prevent them from ever getting breast cancer in the first place. However, many people don't take the medications because they are concerned about side effects. A study was therefore performed in Italy that compared the 5-milligram dose of tamoxifen, which is only one-quarter of the full dose, with placebo for 3 years. After 7 years of follow-up, this low dose of tamoxifen, which is being referred to as “babytam,” was shown to reduce the risk of developing breast cancer by about half, which is similar to the effects seen with the full dose of the medication. Plus, there were fewer side effects. This lower dose is likely to be used regularly for prevention of breast cancer based on these findings, although this lower dose of tamoxifen has not yet been tested to see if it is as effective as the full dose of medication for preventing breast cancer recurrence, so it is not routinely recommended for patients who have a diagnosis of breast cancer to receive this lower dose. Finally, I will touch briefly on exciting results from the POSITIVE trial, which is a trial conducted around the world that examined whether it is safe for young women with hormone receptor-positive breast cancer to stop taking anti-hormone therapy to become pregnant. The women on this trial stopped taking endocrine therapy after taking it for about 18 to 30 months, and then spent up to 2 years trying to become pregnant. About three-quarters of the patients had at least 1 pregnancy during that time, and importantly, there was no increased risk of breast cancer recurrence seen in these patients. Once patients were done with their pregnancy, it was recommended that they restart taking endocrine therapy again. There were a lot of other research findings presented that were related to treatment for both early-stage and metastatic breast cancer at this meeting. Importantly, we got glimpses of the many new drugs on the horizon for treatment of breast cancer, including the 3 that I mentioned already. And we eagerly await the results of large, randomized trials so that the drugs that work can be used to care for patients with breast cancer. But for now, that's it for this quick summary of important research from the 2022 San Antonio Breast Cancer Symposium. Stay tuned to Cancer.Net for future updates from upcoming breast cancer conferences. Thank you. ASCO: Thank you, Dr. Henry. You can find more research from recent scientific meetings at www.cancer.net. Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care. And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

2021 results from the DESTINY-Breast03 study showed that Enhertu (chemical name: fam-trastuzumab-deruxtecan-nxki) more than doubled the 12-month progression-free survival rate compared to Kadcyla (chemical name: T-DM1 or ado-trastuzumab emtansine) in people diagnosed with metastatic HER2-positive breast cancer that had been previously treated. At the 2022 San Antonio Breast Cancer Symposium, Dr. Sara Hurvitz presented new overall survival results, showing that Enhertu also improves overall survival compared to Kadcyla. Listen to the episode to hear Dr. Hurvitz explain: overall survival and progression-free survival results severe side effects of Enhertu how the researchers managed any severe lung problems that developed in people receiving Enhertu

Dr. Sara Tolaney is chief of the Division of Breast Oncology and associate director of the Susan F. Smith Center for Women's Cancers at the Dana-Farber Cancer Institute, as well as associate professor of medicine at Harvard Medical School. The 2021 San Antonio Breast Cancer Symposium featured four days of presentations on the latest research on breast cancer. Dr. Tolaney joined us to discuss the research that is most immediately applicable to people who've been diagnosed with the disease. Listen to the episode to hear Dr. Tolaney explain: results of an early study looking at how effective the experimental medicine datopotamab deruxtecan was in treating metastatic, triple-negative breast cancer a study comparing Enhertu (chemical name: fam-trastuzumab-deruxtecan-nxki) to Kadcyla (chemical name: T-DM1 or ad-trastuzumab emtansine) for metastatic, HER2-positive breast cancer that had spread to the brain the studies that she thinks are practice-changing

Dr. Brian Wojciechowski practices medical oncology in Delaware County, Pennsylvania at Riddle, Taylor, and Crozer hospitals and also serves as Breastcancer.org's medical adviser. A native of South Philadelphia, he trained at Temple University School of Medicine and Lankenau Medical Center. Dr. Wojciechowski is a sought-after speaker on the topics of medical ethics and the biology of cancer. Dr. Wojciechowski joined us to talk about some of the most notable research at the European Society for Medical Oncology Congress 2021. Listen to the episode to hear Dr. Wojciechowski explain: what an antibody-drug conjugate is results from the DESTINY-Breast03 study, showing Enhertu more than doubled the 12-month progression-free survival rate compared to Kadcyla in people diagnosed with metastatic HER2-positive breast cancer that had been previously treated results from the BrighTNess study, showing adding carboplatin to chemotherapy before surgery improves progression-free survival. Running time: 14:09

Dr. Jeffrey Cleland, Ph.D., Chairman, CEO and President of Ashvattha Therapeutics, a clinical stage biotech company discusses treatments that are in development to address inflammation of the brain caused by COVID. They recently announced positive interim results on its ongoing phase 2 PRANA clinical study, which showed that OP-101, a novel hydroxyl dendrimer therapeutic, has the ability to successfully cross the blood brain barrier and suppress hyperinflammation. The company is also developing a class of novel hydroxyl dendrimer therapeutics that they hope will become the future of targeted therapies and unlock new levels of patient care across oncology, ophthalmology, and inflammatory diseases. #AshvatthaTherapeutics Dr. Cleland has 30 years of industry experience in research and development, including more than a decade at Genentech, Inc. His experience in startups includes major roles in obtaining more than $450 million in capital at stages from Series A through D and exit via IPO including over $300 million in capital raised as CEO. As the founding CEO of Versartis (VSAR), he led one of top biotech IPOs of all time. After Versartis, he led the Series B financing and clinical translation of novel Johns Hopkins University technology as CEO of Graybug Vision (GRAY). He held executive management positions at BaroFold, Novacea and Targesome, and has managed directly all aspects of drug development and late-stage research. While at Genentech, Dr. Cleland served in product development and manufacturing roles. He held important leadership roles in the successful approval of two drugs, Herceptin® and Nutropin Depot®, as well as in early work on Lucentis®, Avastin®, and Kadcyla®. He holds a BS in Chemical Engineering from the University of California, Davis and a PhD in Chemical Engineering from the Massachusetts Institute of Technology. Dr. Cleland has authored more than 100 articles and four books, and holds several issued patents. He serves on the Boards of BIO, Exicure, and Zylem and has advisory roles with small emerging biotechnology companies.

What would have been a lung surgery and breast implant explant surgery, turned into the miracle of only needing the explant. But what happened in recovery was shocking to me. A surgery I had put very little merit in, made me go down the rabbit hole of breast implant illness (BII) and thousands of stories of women suffering from it. I was speechless to just how incredible I felt after getting them out and knew I needed to use my platform to share my story, among others that had even more symptoms than me. Join me and Laura Krosky as we talk about the reasons behind us getting our implants out and why we want to share this controversial topic. Breast Implant Illness (BII) Resources:The Inner Circle podcast with Carrie Doll - Healing Breast Implant IllnessBreast Implant Illness Facebook GroupLaura Krosky Resources:Laura on IGLaura Krosky CoachingLaura Krosky Coaching on Facebook Sign up for the next DAC Bootcamp Follow me on Social Media:Amy on IGAmy on Facebook Resources:AmyLedin.comLean Bodies Consulting (LBC)LBC University 

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer. 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses. In this podcast, Cancer.Net Associate Editor Dr. Norah Lynn Henry discusses new research that was presented at the 2018 San Antonio Breast Cancer Symposium, held December fourth through eight in San Antonio, Texas. Dr. Henry is an Associate Professor in the University of Utah's Division of Oncology in the Department of Medicine, and Leader of the Women’s Cancers Disease Center at the Huntsman Cancer Institute. ASCO would like to thank Dr. Henry for discussing this topic. Dr. Henry: Good morning. I am Dr. Lynn Henry, a breast medical oncologist at Huntsman Cancer Institute in Salt Lake City. I would like to share with you one of the exciting breast cancer advances from the 2018 San Antonio Breast Cancer Symposium that was recently held in San Antonio, Texas. First, just a reminder that breast cancer is divided into 3 main categories determined by the presence or absence of receptors on the cancer cell. These categories include hormone receptor positive, HER2-positive, and the so-called triple-negative breast cancer, when all 3 of those main receptors are negative. The study I'm highlighting, which is called KATHERINE, focused specifically on patients with HER2-positive breast cancer. The most commonly used antibody medication used to treat HER2-positive cancer is called trastuzumab, which is also called Herceptin. In the KATHERINE trial, the researchers were testing a different but related drug called trastuzumab emtanzine, which is also called Kadcyla. This new drug is the trastuzumab antibody linked directly to a type of chemotherapy drug. This allows the chemotherapy to be directed specifically to the HER2-positive cancer cells, so it generally causes fewer side effects than typical chemotherapy. Since the generic names of the medications are quite similar, I'm going to refer to them as Herceptin and Kadcyla in the rest of this podcast. Many patients with HER2-positive breast cancer have treatment with chemotherapy and anti-HER2 drugs, like Herceptin, before they undergo surgery in order to try to shrink the cancer and ideally make it all go away. About half of the patients treated this way have no cancer found in their breast or lymph node when they have surgery, but the other half still have cancer remaining. Regardless of what is found at surgery, all patients are usually recommended to have additional treatment with Herceptin after surgery, so they receive a total of 1 year of Herceptin treatment. The KATHERINE trial is important because it asks the question, "Do women who still have cancer left in the breast when they have surgery after chemotherapy and anti-HER2 therapy—do they get more benefit from treatment with Kadcyla, which is Herceptin with the chemotherapy drug, for about 10 months after surgery compared to the standard treatment Herceptin?" In this trial of almost 1500 patients, those who were treated with Kadcyla were much less likely to have their cancer return compared to those treated with Herceptin. The new treatment decreased the risk of cancer returning by about half. Patients with both hormone receptor-positive and hormone receptor-negative breast cancer appeared to benefit from this treatment, however, the downside was that patients treated with Kadcyla had more side effects and were more likely to have to stop the medication because of those side effects. We don't have any information yet about whether or not this new medication will allow patients to live longer following their breast cancer diagnosis, but we do know that it means they're less likely to have their cancers coming back. So how do these findings change treatment recommendations? Before these data were available, oncologists were recommending Herceptin to all patients following surgery. Now, it is likely that once this new medication is approved to be used for this purpose, oncologists will recommend treatment with Kadcyla to those patients who still have cancer remaining at the time of surgery. In terms of what to expect going forward, there are many other trials ongoing to determine how best to treat patients with HER2-positive breast cancer in order to decrease the likelihood of cancer recurrence as much as possible, while also avoiding overtreating those who don't need as much therapy. Well, that's it for this quick summary of this important trial from San Antonio 2018. Overall, we continue on a fast track in breast cancer with many new and exciting therapies being actively studied and research helping support our patients do better than ever before. Stay tuned to Cancer.Net for future updates from upcoming breast cancer conferences. Thank you. ASCO: Thank you, Dr. Henry.  Learn more about breast cancer at www.cancer.net/breast. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play. Cancer.Net is supported by ASCO’s Conquer Cancer Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support.

30% of women who are diagnosed with breast cancer go on to develop secondary breast cancer.  Fiona Leslie is one of them. Sadly there is no cure, but with a positive outlook and by taking the life-extending drug Kadcyla, Fiona is living her life to the full.   Since her diagnosis, the former journalist and now PR professional used her skills to successfully campaign for Kadcyla to be routinely available on the NHS. She’s also a trustee for the charity Second Hope.  I’m sure you’ll agree she’s a true inspiration... For more about Fiona here's her blog: fidancingintherain.wordpress.com If you need more information on Secondary Breast Cancer here are some useful links: secondhope.co.uk breastcancernow.org breastcancercare.org.uk Stay in touch... facebook.com/howshedoesitpodcast instagram.com/how_she_does_it twitter.com/HowShe_Doesit

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