Podcasts about Atezolizumab

european trial phase british columbia clinical urology atezolizumab declan murphy

Play Episode Listen Later Dec 4, 2023 30:29

In this episode, Brian Slomovitz, MD, MS, FACOG, and Keiichi Fujiwara, MD, PhD, share their thoughts and opinions on seminal data presented at the 2023 IGCS annual meeting for endometrial, ovarian, and cervical cancers, including:Phase III NRG GY018 trial of carboplatin and paclitaxel with or without pembrolizumab followed by pembrolizumab or placebo maintenance for 2 years in patients with measurable stage III/IVA, stage IVB, or recurrent endometrial cancer. Phase III ENGOT-EN6/GOG-3031/RUBY trial of carboplatin and paclitaxel with or without dostarlimab followed by dostarlimab or placebo maintenance for 3 years in patients with primary advanced or recurrent endometrial cancer. Results from the double-blind, randomized, placebo-controlled phase III AtTEnd trial of atezolizumab plus carboplatin/paclitaxel in advanced or recurrent endometrial cancer.Randomized, multicenter, double-blind, placebo-controlled phase III DUO-E study of carboplatin and paclitaxel vs durvalumab plus carboplatin and paclitaxel followed by durvalumab maintenance with or without olaparib as frontline treatment of newly diagnosed, advanced, endometrial cancer.An international, randomized, multicenter phase III trial evaluating short-course chemotherapy followed by chemoradiation vs chemoradiation alone in patients with newly diagnosed stage IB1N+, IB2, II, IIIB, IVA squamous, adeno, adenosquamous cervical cancer (INTERLACE).Randomized, double-blind, placebo-controlled phase III KEYNOTE-A18 trial of pembrolizumab plus concurrent chemoradiotherapy vs placebo plus chemoradiation in patients with high-risk locally advanced cervical cancer.Phase III ICON8B study comparing carboplatin, paclitaxel, and bevacizumab every 3 weeks vs dose-dense weekly paclitaxel plus bevacizumab every 3 weeks in newly diagnosed high-risk epithelial ovarian cancer, either stage III (with residual disease or requiring new adjuvant chemotherapy) or stage IV.Presenters:Brian Slomovitz, MD, MS, FACOGDirectorGynecologic OncologyMount Sinai Medical CenterProfessorObsterics and GynecologyFlorida International UniversityMember, Board of DirectorsGOG FoundationUterine Cancer LeadGOG PartnersMiami, Florida Keiichi Fujiwara, MD, PhDProfessor of Gynecologic OncologySaitama Medical University International Medical CenterHidaka, JapanProfessor of OBGYNInternational University of Health and WelfareNarita, JapanThis educational activity is supported by educational grants from AstraZeneca, Genmab, GlaxoSmithKline, Merck Sharp & Dohme Corp, Novocure, and Seagen. Link to full program, including a downloadable highlights slideset and ClinicalThought commentaries:https://bit.ly/424E3Uq

December 2023 | European Urology Highlights

European Urology Podcast

Play Episode Listen Later Dec 1, 2023 36:38

More great highlights from the latest edition of European Urology!! Here on the European Urology Podcast we bring you selected highlights each month with some great guests. As ever we highlight two key papers (details below) from this month's journal, including interviews with key authors and expert commentators. We also look at other highlights in this month's journal with guest contributor Dr Bernard Jansen (Amsterdam). Declan Murphy hosting on his own this week as co-Host Joyce Baard couldn't make it. But Joyce will be back for our first podcast in 2024!!Even better on our YouTube channelPodcast Priority Papers1. Phase 2 Trial of Atezolizumab in Bacillus Calmette-Guérin–unresponsive High-risk Non–muscle-invasive Bladder Cancer: SWOG S1605 Featured author - Dr Peter Black (University of British Columbia, Vancouver)Discussant - Dr Carmen Mir (La Ribera University Hospital, Valencia)2. Clinical and Genomic Differences Between Advanced Molecular Imaging-detected and Conventional Imaging-detected Metachronous Oligometastatic Castration-sensitive Prostate Cancer Featured author - Dr Philip Sutera (Johns Hopkins University, Baltimore)Discussant - Dr Giorgio Ganglia (San Raffaele University, Milano)Full index to European Urology December 2023

Expert Insight on Key Updates and New Clinical Trial Data From the ESMO 2023 Congress Informing Treatment for Endometrial, Ovarian, and Cervical Cancers

Medscape InDiscussion: Melanoma

Play Episode Listen Later Nov 17, 2023 33:18

In this episode, Isabelle Ray-Coquard, MD, PhD, and Ana Oaknin, MD, PhD, provide expert insights on new clinical trial data presented at the 2023 ESMO annual congress for endometrial, ovarian, and cervical cancers, including:Results from the double-blind, randomized, placebo-controlled phase III AtTEnd trial of atezolizumab plus carboplatin/paclitaxel in advanced or recurrent endometrial cancerRandomized, multicenter, double-blind, placebo-controlled phase III DUO-E study of durvalumab plus carboplatin and paclitaxel followed by durvalumab maintenance with or without olaparib as frontline treatment of newly diagnosed, advanced, endometrial cancerFirst results from a phase II biomarker-directed platform study with assigned treatments for patients with measurable persistent or recurrent platinum-resistant epithelial ovarian cancer based on tumor-specific molecular alterations (ENGOT-GYN/GOG-3051/BOUQUET)Randomized, double-blind, placebo-controlled phase III KEYNOTE-A18 trial of pembrolizumab plus concurrent chemoradiotherapy in patients with high-risk locally advanced cervical cancerAn international, randomized, multicenter phase III trial evaluating short-course chemotherapy followed by chemoradiation vs chemoradiation alone in patients with newly diagnosed stage IB1N+, IB2, II, IIIB, IVA squamous, adeno, adenosquamous cervical cancer (INTERLACE)Primary results from the global, randomized phase III BEATcc trial of atezolizumab plus platinum-based chemotherapy + bevacizumab as frontline treatment in patients with persistent, recurrent, or metastatic cervical cancerInterim analysis results from the global, randomized, open-label phase III innovaTV 301 study of tisotumab vedotin vs investigator's choice of chemotherapy in second-line or third-line recurrent/metastatic cervical cancerPresenters:Ana Oaknin, MD, PhDHead of Gynaecologic Cancer ProgrammeDepartment of Medical OncologyVall d' Hebron University HospitalVall d'Hebron Institute of OncologyBarcelona, SpainIsabelle Ray-Coquard, MD, PhDPresident of the Gineco GroupCentre Leon BérardLaboratories RESHAPE Université Claude Bernard Lyon EstLyon, FranceThis educational activity is supported by educational grants from AstraZeneca, Genmab, GlaxoSmithKline, Merck Sharp & Dohme Corp, Novocure, and Seagen. Link to full program, including a downloadable highlights slideset and ClinicalThought commentaries:https://bit.ly/424E3Uq

Treatment Options Before and After Surgery for Early-Stage Non-Small Cell Lung Cancer

Cancer.Net Podcasts

Play Episode Listen Later Nov 7, 2023 31:11

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 voice of the world's oncology professionals. 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. Guests' statements on this 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. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses. In this podcast, Cancer.Net Associate Editor for Lung Cancer, Dr. Charu Aggarwal, and Cancer.Net Specialty Editor for Thymoma, Dr. Ryan Gentzler, discuss what people with early-stage non-small cell lung cancer should know about their treatment options before and after surgery, called neoadjuvant therapy and adjuvant therapy, respectively. Dr. Aggarwal is the Leslye Heisler Associate Professor of Medicine in the Hematology-Oncology Division at the University of Pennsylvania's Perelman School of Medicine. Dr. Gentzler is a thoracic medical oncologist and Associate Professor of Medicine in the Division of Hematology/Oncology at the University of Virginia (UVA) Comprehensive Cancer Center. View disclosures for Dr. Aggarwal and Dr. Gentzler at Cancer.Net. To begin, Dr. Gentzler will discuss what people with early-stage non-small cell lung cancer should know about neoadjuvant treatment options before lung surgery. Welcome, Dr. Gentzler. Dr. Gentzler: Hi, this is Ryan Gentzler from the University of Virginia. We're here to discuss the role of neoadjuvant chemotherapy and immunotherapy for the treatment of locally advanced non-small cell lung cancer. So first, I thought I'd address some of the data and definition of what is neoadjuvant treatment. So when we think about treating lung cancer that is not metastatic, that is earlier stage disease, there typically involves multimodality treatment. Sometimes these lesions or tumors can be very small and can be stage I and treated with surgery alone or perhaps radiation alone and no further treatment is needed. But the vast majority of lung cancers that are considered early stage are in fact either larger tumors, involve lymph nodes, and typically fall into the category of stage II or III lung cancers. And these are cancers that often require multiple treatments beyond the local surgery approach alone. When we think about how we deliver that treatment, it can either be given before surgery or after a surgery. If we give treatment before a surgery, we call that neoadjuvant. If it is given after the surgery, we call that adjuvant. And most of the data that we have today in lung cancer uses one or the other of these approaches, and we don't typically give treatments both before and after, at least in terms of the chemotherapy part of that treatment. Historically, most of the data exists in the adjuvant treatment of lung cancer going back several decades that showed that the benefit of chemotherapy after a surgery, particularly for those with stage II and stage III lung cancer, derived a clear benefit of survival by giving chemotherapy after surgery. More recently, with the advent of immune therapy, which we have used in patients with stage IV lung cancer as well as those with stage III lung cancer who cannot undergo surgery, those immunotherapy drugs have been shown to improve overall survival and improve clinical outcomes for a wide range of patients with more advanced disease. And so in the last 4 or 5 years, we have really looked at new trials that have added immunotherapy in what we call perioperative space, either before surgery or after surgery for those that have surgically resectable disease. I'm going to focus on the neoadjuvant approaches that we have seen today, and this largely all started with data from Patrick Forde out of Johns Hopkins and Jamie Chaft from Memorial Sloan Kettering looking at single agent treatment with nivolumab immunotherapy. This was no chemotherapy given for 3 treatments prior to or three cycles prior to surgery. And that trial demonstrated a high degree of patients with tumor reduction and more importantly, we saw that the pathologic response, meaning how much tumor was left under the microscope at the time of surgery, was higher than what anyone anticipated with just immunotherapy alone. That launched a whole series of larger randomized prospective trials evaluating largely the combination of chemotherapy and immune therapy prior to surgery. Now, before we get into some of the results of these trials, I really wanted to emphasize some of the theoretical advantages to neoadjuvant approach. Now, the first potential advantage of giving neoadjuvant treatment is that we know when you start with immunotherapy and chemotherapy regimens and that's the first type of treatment, everyone is guaranteed to get that treatment. And we know that the completion rate prior to surgery is higher than it is after surgery. These patients can get all of the prescribed treatment and will be more likely to get it than if they get it after surgery. So this is one advantage. The other is potentially starting these medications which go throughout the body and treat the cancer, wherever it may be, earlier. We know that one of the risks of all cancers, but lung cancer in particular, is that even with good surgery and removing all of that cancer, there is a chance that there are cancer cells left behind, which leads to risk of recurrence in the years to come after surgery. Naturally, if we start the treatment that can eliminate those cancer cells, wherever they may be, and do that first, perhaps we catch this earlier with fewer cells that have escaped and have a more likely chance of success of eliminating the cancer and resulting in a cure. The third, I think, is one that we still have yet to learn more about, but if we give immunotherapy in particular, these are medications that activate the immune system, particularly the type of immune system cell called a T cell. If that T cell is able to recognize tumor cells, it is more likely to be able to continue to attack those tumor cells. And if we give that treatment prior to removal of the tumor, perhaps that activates the immune system in a more robust way that it can go after these cancer cells and eliminate those that are left behind after the surgery. If you give the immunotherapy after a surgery and the bulk of the tumor, most of the cancer cells have been removed, it may be harder to find those antigens or foreign proteins that are expressed in cancer cells. So the immune system may not be as robustly able to go after cancer if you give it solely after a surgery. Another potential advantage of neoadjuvant approaches is that it really helps us learn as oncologists how well a cancer is responding to a treatment. If we give these treatments for 4 cycles after a surgery, we don't know whether it's eliminating those residual cancer cells or whether it is totally ineffective. If we give it before a surgery and we see that there is tumor reduction or that there is a complete elimination of the cancer, we know that that treatment was an effective treatment at attacking the cancer cells and eliminating them. We know that the cancer was sensitive to that treatment. We can then better prognosticate how well the patients are going to do after surgery. We know based on the latest data that if you achieve what we call a pathologic complete response with chemotherapy and immunotherapy prior to surgery, meaning there are no cancer cells left when we look at that surgical specimen under the microscope, we know that those patients have a much better likelihood of surviving for longer periods of time than those who have active cancer at the time of surgery after prior treatment. And so neoadjuvant approaches allow us in a 2-month time frame to get a great sense of how well our treatments are working and able to prognosticate outcomes based on how well those cancer cells have been eliminated at the time of surgery. One large phase 3 trial called the CheckMate 816 trial was a randomized phase 3 trial and that enrolled patients with stage IB through IIIA non-small cell lung cancer using the old staging system of the 7th edition. These would all now be categorized as stage II and stage III non-small cell lung cancer patients. And it randomized these patients to 3 cycles of chemotherapy plus nivolumab, which is an immunotherapy drug, and compared that to patients treated with chemotherapy alone for 3 cycles. After these 3 cycles of chemotherapy, which is about a 9-week time frame, patients had surgical resection of their tumors. And then after surgery, patients received no further treatment, although treating physicians were allowed to give additional treatments like chemotherapy or radiation if they thought it would be beneficial for these patients, although it was not mandated by the study. One of the first results we saw from this study was that there was a much higher rate of pathologic complete response of 24% of patients achieving a path CR [pathologic complete response] with the nivolumab plus chemotherapy combination compared to only 2.2% with chemotherapy alone. This was highly statistically significant and demonstrated a clear benefit for those receiving the immunotherapy. The other main endpoint of this study was event-free survival, meaning that the time that the patients were alive and without any significant event like cancer progression or death after the enrollment of the trial. And in this analysis, the median event-free survival was significantly longer in those who have received the immunotherapy plus chemotherapy combination prior to surgery. One of the potential concerns about neoadjuvant treatment is that it may render patients unfit for surgery who otherwise could have had their cancer removed. When we look at the outcomes from this CheckMate 816 trial, it actually did not appear to be the case to a large degree. In fact, those that got the nivolumab plus chemotherapy combination were more likely to proceed on with surgery, and the majority did; 83% received the planned surgery. There were patients who were unable to receive surgery due to adverse events of their treatment, but that was only 1% of patients enrolled in the trial. Other reasons for canceling the surgery included disease progression, meaning the cancer got worse to the point where they could not undergo surgery, or other reasons, such as the patient declined surgery, or it was found to be unresectable at the time the surgeon wanted to remove the cancer, or poor lung function. One of the insights we got from the surgical data from this trial were that those who received the combination of chemotherapy and immunotherapy had slightly higher rates of smaller surgeries like a lobectomy compared to a pneumonectomy for those who had received [chemotherapy alone.] There were also fewer numbers of patients who required a conversion from a minimally invasive surgical procedure to an open surgical procedure if they were getting the immunotherapy combination. A higher number of patients also were able to have complete resection of their tumor if they received the immunotherapy/chemotherapy combination. The length of hospitalization was slightly lower, and the rates of pain were slightly lower in those who received the combination as well. These comparisons were not statistically significantly different, but numerically, there seems to be at least a trend toward benefit in surgical outcomes in this neoadjuvant chemotherapy/immunotherapy approach. And I think this makes sense. We know that this combination is more able to eliminate a cancer and make it a pathologic complete response when we look at it under the microscope, and therefore, if there is shrinking the tumor to a higher degree, naturally, it seems there would be more likely of completely removing the tumor, using a smaller incision to remove that tumor, shortening the length of stay in the hospital and recovery time and pain control. All makes sense if we know that the treatment itself is able to reduce that size of the tumor. There are many other phase 3 trials ongoing studying the impact of immunotherapy plus chemotherapy in the neoadjuvant setting. The AEGEAN trial has recently reported data at the AACR meeting this year in 2023 with similar results that we saw with the CheckMate 816 trial. There are 3 other phase 3 trials that are ongoing, one of which we will see later this summer called the KEYNOTE-671 trial evaluating pembrolizumab plus chemotherapy in the neoadjuvant setting and then 2 other trials evaluating nivolumab, the CheckMate 77T trial, or atezolizumab in the IMpower030 trial. Each of these more recent trials typically have used 4 cycles of chemotherapy plus immunotherapy prior to surgery and also continued the immunotherapy after surgery for a period of time, most commonly approximately 1 year. From the data we have seen so far, it remains uncertain whether additional immunotherapy beyond the 3 or 4 cycles given in the neoadjuvant setting provides any additional benefit. We still do not understand what to do with patients who did not achieve a pathologic response whether further treatment would be of any additional benefit. We do not know if there will be further benefit even in those that achieved a pathologic complete response whether a slightly longer duration of immunotherapy would further improve outcomes in that group. We suspect with longer-term follow-up over the years of all of these phase 3 trials that some of these questions will be answered. So what are some key questions that patients should ask when considering a neoadjuvant chemotherapy/immunotherapy approach? I think the first question that's key is what is my tumor stage? We know that the trials that enrolled patients with a neoadjuvant approach enrolled patients using our current staging system would be a stage II or stage III lung cancer. And this is where it gets really tricky is, what subdivision of stage III is it? We tend to think of stage IIIA's as being one that it would be surgically resectable, with a smaller number of stage IIIBs, and then stage IIIC, one that we would not typically recommend surgery for. I think the next question within the tumor stage is, is this based on imaging or based on the biopsies? And we know that biopsies are really the best way to stage locally advanced cancers, particularly getting samples of lymph nodes in the mediastinum. Sometimes what looks like a stage I or stage II on imaging is, in fact, a stage III based on biopsies that are done at the time of surgery. It's ideal to know that information prior to making the decision about surgery so that that surgery is not futile. On the opposite side, sometimes there is imaging suggestive of lymph nodes that are enlarged in the mediastinum, and it's presumed that this is a more advanced stage III and is not surgically resectable. However, if you go and biopsy those lymph nodes, sometimes they are benign. Sometimes they are inflammation related to infection or cancer but do not actually contain cancer cells. And so we typically advise that getting biopsies of lymph nodes in the mediastinum, at least any that are particularly suspicious, is highly recommended for these locally advanced cancers. I think the next question that's key to ask is, what are my tumor biomarkers? And there are multiple biomarkers that we look at in non-small cell lung cancer that help us decide what is the best treatment. What is the best approach? What is the best medicine to treat the cancer? We know that one of these biomarkers that is a key is a mutation. So multiple different mutations can occur in lung cancers, particularly those that are adenocarcinoma subtypes. And these mutations may be less likely to benefit from immunotherapy and we may want to take a different approach with surgery, chemotherapy, and potentially targeted therapies that specifically target that mutation that exists in the tumor. The other key biomarker here is PD-L1. We know that tumors with a higher level of PD-L1 are more likely to respond and benefit from immunotherapy. As of right now, that PD-L1 status plays a more important role in the adjuvant setting. All of the chemotherapy plus immunotherapy combinations in the neoadjuvant setting seem to benefit the group as a whole regardless of that PD-L1 status. But still, an important biomarker that we should have prior to making all final decisions on treatment. I think another question that should be asked any time you have an earlier stage cancer is, is my tumor surgically resectable? And there can be many reasons why cancers are not resectable, perhaps due to the anatomy of where the tumor is located, if it invades into the mediastinum, for example, or is near large blood vessels, or perhaps because there are too many lymph nodes and this is a more advanced stage. And so I think the main reasons for not being surgically resectable would be the tumor is too large, if the stage is too high, or is it more of a function of fitness for surgery and that can be because of other underlying lung disease. Perhaps removing part or all of a lung would not be safe due to impaired lung function to begin with. And I think it's important to understand that sometimes stage III lung cancers are resectable and sometimes they are not, and understanding the reason why they are not, I think, is important. And then I think lastly and ultimately when we're talking about a neoadjuvant approach, you want to ask your treating oncologist, "Would it be better to give my treatment before surgery or after surgery?" And really discuss the pros and cons with the physician and have them incorporate all of the factors that go into these treatment decisions. How well you'll tolerate chemotherapy, other medical conditions that may play a role in the likeliness of getting through those treatments safely, perhaps underlying diseases that may increase the risk of immune-related side effects with immunotherapy. You really want to factor in all of these things and discuss the pros and cons of a systemic treatment first versus surgery first before making final decisions on how to treat locally advanced lung cancer. All right. Thank you. ASCO: Thank you, Dr. Gentzler. Next, Dr. Aggarwal will discuss what people with early-stage non-small cell lung cancer should know about their adjuvant treatment options for after lung surgery. Dr. Aggarwal: This is Dr. Charu Aggarwal. I'm the Leslye Heisler Associate Professor for Lung Cancer Excellence at University of Pennsylvania's Abramson Cancer Center. And today I will talk to you about the use of adjuvant immunotherapy in the setting of early-stage non-small cell lung cancer. We'll start by discussing what adjuvant therapy is, what types of options we have for adjuvant therapy, what kind of testing is important, and what options there may be in terms of adjuvant immunotherapy. So let's get started. Early-stage lung cancer comprises of stages between stage I to stage III. These stages vary by the size of the tumor as well as the level of lymph node involvement. In the setting of very early-stage lung cancer, such as stage I and stage II, as well as some select stage III lung cancers, we recommend surgical resection. And in these patients, the use of additional treatment is recommended based upon the pathological determination of the tumor size as well as the lymph node status. If usually lymph nodes are involved, we recommend adjuvant chemotherapy, and also, many experts will deliver adjuvant chemotherapy for tumors that may be larger than 4 centimeters even in the absence of lymph node involvement. The data for adjuvant chemotherapy comes from several large clinical trials that were conducted about a couple of decades ago now that demonstrated not only an improvement in preventing recurrence of the cancer but also a modest improvement in overall survival, really laying the ground for improvement and therefore becoming the gold standard. Four cycles of chemotherapy are usually administered about 6 to 12 weeks following surgical resection, and this is really the basis of our treatment in the early-stage setting. In today's time and age, we now have several other options. We have treatment options that include molecular therapy, which is biomarker driven, as well as the use of immunotherapy. So it's actually very important for us in the adjuvant setting--or in the post-surgical setting--to test for mutations such as EGFR. It's also important for us to test PD-L1 status. So let's dive into why each of these may be important. Patients with EGFR mutations, especially those with sensitizing mutations in EGFR exon 19 or 21, now have the opportunity to receive a targeted therapy in the form of osimertinib, which is an oral drug, very targeted and specific for the EGFR mutation that has been studied in a clinical trial setting in patients with early-stage non-small cell lung cancer. In patients with stage IB to IIIA non-small cell lung cancer with EGFR mutation, use of osimertinib was associated with a significant improvement in our ability to delay the recurrence of cancer. Based on this significant improvement, FDA approved therapy with osimertinib, and it is currently available and ready to use. We usually recommend it for 3 years, so daily therapy for 3 years, and patients are monitored with routine CAT scans and lab work. For patients who don't have an EGFR mutation, we do recommend broad panel testing. Of course, this is not the standard, but I think it's important for us to identify patients who may not benefit from immunotherapy. Patients that have an ALK mutation, for example, or ROS1 translocation, may not have the best chances of responding to adjuvant immunotherapy, and therefore, I think testing should be performed to make sure that we are having a shared decision-making conversation with our patients about the use of the correct adjuvant options. In terms of adjuvant immunotherapy, we now have 2 approved agents. One of them is atezolizumab, and the other one that was just recently approved is pembrolizumab. Atezolizumab was approved on the basis of a large clinical trial called the IMpower010 study, which randomized 1,280 patients with stage IB to IIIA non-small cell lung cancer to either 1 year of atezolizumab or best supportive care. Of note, all of these patients had to have had adjuvant chemotherapy that included a cisplatin platinum chemotherapy. In the first analysis, we found that the disease-free survival or the probability of the patients remaining cancer-free was significantly improved in those patients that had a tumor expression of PD-L1 greater than or equal to 1% and received atezolizumab compared to patients who did not receive atezolizumab. On the basis of this positive primary endpoint, the U.S. FDA approved the use of adjuvant atezolizumab for patients with stage II to IIIA resected non-small cell lung cancer after surgical resection and adjuvant chemotherapy. Recently, we heard that this does lead to small but significant improvement in overall survival. There is a trend towards improvement in overall survival. However, the data are quite immature at this point, and we do need longer follow-up to be able to follow this trend. The greatest magnitude of overall survival benefit was found in patients who had the PD-L1 greater than or equal to 50%. So it's important to know what the PD-L1 level of a patient may be when I'm thinking about adjuvant immunotherapy because adjuvant immunotherapy is most likely to benefit those that don't have an actionable mutation, such as EGFR, and those that have the highest PD-L1 staining, at least in the IMpower trial. Secondly, the PEARLS clinical trial is a clinical trial that evaluated the use of pembrolizumab, which is another immunotherapy agent, again, in the adjuvant setting. For this clinical trial as well, there was a small but significant improvement in disease-free survival, again preventing the probability of recurrence in all patients that received pembrolizumab compared to the best supportive care. And basically, this led to also an approval by the FDA for the use of pembrolizumab. Again, now we have 2 options. Both of these are administered for 1 year. What should patients know about therapy? These drugs are usually administered once every 3 weeks. They are given intravenously. Sometimes, we can change the treatment schedule to be either once every 4 weeks in the case of atezolizumab or every 6 weeks in the case of pembrolizumab. These may be associated with some side effects. Immunotherapy side effects that are most common are fatigue, chills, myalgias, or basically a feeling of pains in the body or joints. But also, some serious life-threatening reactions can occur such as activation of the immune system to such an extent that the immune system may start to attack the body's organs. So this may lead to swelling or inflammation in the organs that may manifest itself as colitis if the gut gets inflamed, or pneumonitis if the lungs were to get inflamed, or pancreatitis if the pancreas were to get inflamed. Any organ in the body can really get inflamed. We've certainly seen cases of thyroiditis. We've seen cases of polyarthritis. We've seen cases where the brain may also get inflamed or the pituitary may get inflamed. So there are definitely some life-threatening reactions or side effects that can occur with the use of immunotherapy that should be closely monitored. The benefit of having used immunotherapy in the metastatic setting is that now we have a lot of experience managing these side effects. And if recognized early, these side effects can be managed appropriately with the use of steroids as well as holding therapy. Many of the times, we can even reinstitute immunotherapy without significant harm to the patients. However, I think immunotherapy benefits as well as side effects should be discussed in detail with the provider, especially in the adjuvant setting. Patients may ask if neoadjuvant immunotherapy along with chemotherapy is a better approach compared to adjuvant immunotherapy. At this time, we don't have a clinical trial that is comparing neoadjuvant chemoimmunotherapy followed by surgery to an approach that is surgery followed by adjuvant immunotherapy. In general, I would say that if the decision by a multidisciplinary team has been made to proceed with surgery, careful discussion should be had about adjuvant chemotherapy as well as the use of adjuvant immunotherapy, and molecular testing should be performed. All patients with early-stage disease should have a multidisciplinary tumor board discussion, which includes engagement with surgeons, radiation oncologists, pulmonologists, pathologists, and medical oncologists so that they can ensure that many experts have had the chance to weigh into their case as well as come to the right conclusion on whether or not to use new adjuvant chemoimmunotherapy or just to proceed with surgical resection. ASCO: Thank you, Dr. Aggarwal. You can learn more about neoadjuvant and adjuvant treatment options for early-stage non-small cell lung cancer at www.cancer.net/lung. 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.

How Do You Choose Treatment in the Frontline Setting for Metastatic Melanoma?

Play Episode Listen Later Jun 15, 2023 31:40

Drs Sapna Patel and Yana Najjar analyze the data and share their approach to frontline therapy. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/989035). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Combination Dabrafenib and Trametinib Versus Combination Nivolumab and Ipilimumab for Patients With Advanced BRAF-Mutant Melanoma: The DREAMseq Trial-ECOG-ACRIN EA6134 https://pubmed.ncbi.nlm.nih.gov/36166727/ Sequencing of Ipilimumab Plus Nivolumab and Encorafenib Plus Binimetinib for Untreated BRAF-Mutated Metastatic Melanoma (SECOMBIT): A Randomized, Three-Arm, Open-Label Phase II Trial https://pubmed.ncbi.nlm.nih.gov/36049147/ Long-Term Outcomes of Patients With Active Melanoma Brain Metastases Treated With Combination Nivolumab Plus Ipilimumab (CheckMate 204): Final Results of an Open-Label, Multicentre, Phase 2 Study https://pubmed.ncbi.nlm.nih.gov/34774225/ Health-related Quality of Life With Nivolumab Plus Relatlimab Versus Nivolumab Monotherapy in Patients With Previously Untreated Unresectable or Metastatic Melanoma: RELATIVITY-047 Trial https://pubmed.ncbi.nlm.nih.gov/37167764/ Overall Survival With Combined Nivolumab and Ipilimumab in Advanced Melanoma https://pubmed.ncbi.nlm.nih.gov/28889792/ Evaluation of Two Dosing Regimens for Nivolumab in Combination With Ipilimumab in Patients With Advanced Melanoma: Results From the Phase IIIb/IV CheckMate 511 Trial https://pubmed.ncbi.nlm.nih.gov/30811280/ Adjuvant Therapy of Nivolumab Combined With Ipilimumab Versus Nivolumab Alone in Patients With Resected Stage IIIB-D or Stage IV Melanoma (CheckMate 915) https://pubmed.ncbi.nlm.nih.gov/36162037/ Single-Agent PD-1 Blockade Is "Treatment of Choice" for Desmoplastic Melanoma https://pubmed.ncbi.nlm.nih.gov/37071762/ Single-agent Pembrolizumab May Benefit Patients With Rare Type of Skin Cancer https://www.aacr.org/about-the-aacr/newsroom/news-releases/single-agent-pembrolizumab-may-benefit-patients-with-rare-type-of-skin-cancer/ Atezolizumab, Vemurafenib, and Cobimetinib as First-Line Treatment for Unresectable Advanced BRAFV600 Mutation-Positive Melanoma (Imspire150): Primary Analysis of the Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/32534646/ Overall Survival Benefit With Tebentafusp in Metastatic Uveal Melanoma https://pubmed.ncbi.nlm.nih.gov/34551229/ Efficacy and Safety of Nivolumab Alone or in Combination With Ipilimumab in Patients With Mucosal Melanoma: A Pooled Analysis https://pubmed.ncbi.nlm.nih.gov/28056206/ Single-Agent Anti-PD-1 or Combined With Ipilimumab in Patients With Mucosal Melanoma: An International, Retrospective, Cohort Study https://pubmed.ncbi.nlm.nih.gov/35716907/ CheckMate 067: Long-Term Outcomes in Patients With Mucosal Melanoma. https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.10019 A Randomized Phase 2 Trial of Encorafenib + Binimetinib + Nivolumab Vs Ipilimumab + Nivolumab In BRAFV600-Mutant Melanoma Brain Metastases https://www.swog.org/clinical-trials/s2000

Episode 245: ASCO 2023 - CONTACT-03 cabozantinib +/- atezolizumab in renal cancer

The Uromigos

Play Episode Listen Later Jun 5, 2023 27:46

Toni Choueiri describes the results of this renal cancer trial exploring rechallange with immune therapy

cancer renal asco atezolizumab cabozantinib toni choueiri

Gastroesophageal and Hepatobiliary Cancers | Cases from the Community: Investigators Discuss Available Research Guiding the Care of Patients with Gastroesophageal and Hepatobiliary Cancers — A 2023 Post-ASCO GI Webcast

Research To Practice | Oncology Videos

Play Episode Listen Later Apr 4, 2023 60:32

Featuring perspectives from Drs Eric Lee, Neil Morganstein and Swati Vishwanathan, including the following topics: • Gastroesophageal Cancers — Zev Wainberg, MD, MSc o Introduction (0:00) o Systemic therapy considerations for HER2-negative localized gastroesophageal cancers (4:33) o First-line systemic therapy for metastatic esophageal or gastric cancer (10:05) o Zolbetuximab/chemotherapy as first-line treatment for HER2-negative, locally advanced unresectable or metastatic gastric and gastroesophageal junction cancers (16:19) o Repeat tissue biopsy versus circulating tumor DNA testing for HER2-positive GI cancers after disease progression on first-line therapy (20:59) o Trastuzumab deruxtecan as second-line therapy for HER2-positive gastric cancer; management of CNS disease (25:05) • Hepatobiliary Cancers — Lipika Goyal, MD, MPhil o Tissue biopsy for suspected hepatocellular carcinoma (HCC) (29:59) o Atezolizumab/bevacizumab versus durvalumab/tremelimumab as first-line therapy for HCC; disease etiology and response to treatment (33:34) o Liver-directed therapy in the era of effective novel systemic regimens (40:50) o First-line, single-agent immunotherapy for HCC (44:33) o Sequencing tyrosine kinase inhibitors for patients with HCC with and without contraindications to immunotherapy (47:46) o Survival benefit with durvalumab/gemcitabine/cisplatin for advanced biliary tract cancers (BTCs) in the TOPAZ-1 trial — A new standard? (51:25) o Spectrum of targetable genetic alterations in BTCs; novel FGFR2 inhibitors for cholangiocarcinoma (54:28) CME information and select publications

FDA D.I.S.C.O. Burst Edition: FDA approvals of Tecentriq (atezolizumab) for unresectable or metastatic alveolar soft part sarcoma, and Krazati (adagrasib) for KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer

FDA Drug Information Soundcast in Clinical Oncology (D.I.S.C.O.)

Play Episode Listen Later Jan 23, 2023 6:59

Listen to a soundcast of the December 9 and 12, 2022, FDA approvals of Tecentriq (atezolizumab) for unresectable or metastatic alveolar soft part sarcoma, and Krazati (adagrasib) for KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer”

soft fda disc locally burst approvals metastatic sarcoma kras mutated small cell lung cancer alveolar unresectable atezolizumab

MPR Weekly Dose 145 — COVID-19 Vaccine Investigation; HIV Vaccine Lacks Efficacy; Sepsis Diagnostic Test; RSV-Associated Disease Vaccine; Combo Tx Reduces CA Recurrence

MPR Weekly Dose

Play Episode Listen Later Jan 20, 2023 13:08

Pfizer-BioNTech bivalent vaccine under investigation; Trial evaluating HIV prevention vaccine discontinued; Early detection sepsis test cleared; Trial results for RSV-associated disease vaccine; Combo Tx for HCC recurrence shows promise

Individualizing Care for Patients With Triple-Negative Breast Cancer

Medscape InDiscussion: Renal Cell Carcinoma

Play Episode Listen Later Jan 18, 2023 36:17

In this podcast episode from a live CCO Cancer Conversations webinar, Mark Pegram, MD, and Sara Tolaney, MD, MPH, provide expert perspectives on optimal treatment strategies for patients with triple-negative breast cancer (TNBC), with topics including:Current data and strategies for using PD-1/PD-L1 inhibitors in early-stage TNBC Clinical implications of PD-L1 status on therapeutic planning for patients with metastatic TNBC Current data and treatment strategies and the future of antibody–drug conjugates in the management of relapsed/refractory advanced TNBC Treatment implications of the presence of BRCA1/2 mutations and homologous recombination deficiency genes in advanced TNBCRole of PARP inhibitors in the treatment of TNBCPresenters: Mark Pegram, MDProfessor Medical OncologyStanford UniversityPalo Alto, CaliforniaSara Tolaney, MD, MPHAssociate Professor of MedicineDivision of Breast OncologyHarvard Medical SchoolChief, Division of Breast OncologyBreast Oncology ProgramDana-Farber Cancer InstituteBoston, MassachusettsContent based on an online CME/CE/CPE program supported by educational grants from Gilead Sciences, Inc.Link to full program:http://bit.ly/3iQzDz5

Second-Line Treatment of Renal Cell Carcinoma

Play Episode Listen Later Jan 5, 2023 20:41

Drs Sumanta Pal and Martin Voss discuss second-line treatment of renal cell carcinoma, including current studies and agents used in the refractory setting. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968745). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Renal Cell Carcinoma Treatment & Management https://emedicine.medscape.com/article/281340-treatment Comparative Effectiveness of Axitinib Versus Sorafenib in Advanced Renal Cell Carcinoma (AXIS): A Randomised Phase 3 Trial https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61613-9/fulltext Cabozantinib Versus Everolimus in Advanced Renal-Cell Carcinoma https://www.nejm.org/doi/full/10.1056/NEJMoa1510016 CANTATA: Primary Analysis of a Global, Randomized, Placebo (Pbo)-Controlled, Double-Blind Trial of Telaglenastat (CB-839) + Cabozantinib Versus Pbo + Cabozantinib in Advanced/Metastatic Renal Cell Carcinoma (mRCC) Patients (pts) Who Progressed on Immune Checkpoint Inhibitor (ICI) or Anti-Angiogenic Therapies. https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.4501 FDA Approves Tivozanib for Relapsed or Refractory Advanced Renal Cell Carcinoma https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tivozanib-relapsed-or-refractory-advanced-renal-cell-carcinoma Tivozanib Versus Sorafenib in Patients With Advanced Renal Cell Carcinoma (TIVO-3): A Phase 3, Multicentre, Randomised, Controlled, Open-Label Study https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30735-1/fulltext Lenvatinib, Everolimus, and the Combination in Patients With Metastatic Renal Cell Carcinoma: A Randomised, Phase 2, Open-Label, Multicentre Trial https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00290-9/fulltext A Study of Atezolizumab in Combination With Cabozantinib Compared to Cabozantinib Alone in Participants With Advanced Renal Cell Carcinoma After Immune Checkpoint Inhibitor Treatment (CONTACT-03) https://clinicaltrials.gov/ct2/show/NCT04338269 TiNivo: Safety and Efficacy of Tivozanib-Nivolumab Combination Therapy in Patients With Metastatic Renal Cell Carcinoma https://linkinghub.elsevier.com/retrieve/pii/S0923-7534(20)42472-X Kidney Cancer Research Summit https://kcrs.kidneycan.org/

Plasma Growth Hormone in HCC as Biomarker of Response to Atezolizumab & Bevacizumab

Oncotarget

Play Episode Listen Later Dec 22, 2022 3:49

A new research paper was published in Oncotarget's Volume 13 on December 6, 2022, entitled, “Plasma growth hormone is a potential biomarker of response to atezolizumab and bevacizumab in advanced hepatocellular carcinoma patients.” Hepatocellular carcinoma (HCC) has limited systemic therapy options when discovered at an advanced stage. Thus, there is a need for accessible and minimally invasive biomarkers of response to guide the selection of patients for treatment. In this new study, researchers Yehia I. Mohamed, Dan G. Duda, Muhammad O. Awiwi, Sunyoung S. Lee, Lina Altameemi, Lianchun Xiao, Jeffrey S. Morris, Robert A. Wolff, Khaled M. Elsayes, Rikita I. Hatia, Aliya Qayyum, Shadi M. Chamseddine, Asif Rashid, James C. Yao, Armeen Mahvash, Manal M. Hassan, Hesham M. Amin, and Ahmed Omar Kaseb from MD Anderson Cancer Center, Massachusetts General Hospital, Harvard Medical School, Michigan State University, University of Pennsylvania, and Perelman School of Medicine investigated the biomarker value of plasma growth hormone (GH) level as a potential biomarker to predict outcome in unresectable HCC patients treated with current standard therapy, atezolizumab plus bevacizumab (Atezo/Bev). “The present study was designed to investigate the association between GH levels and overall survivals (OS) and progression free survival (PFS) in HCC patients treated with current standard, atezolizumab plus bevacizumab.” The study included unresectable HCC patients scheduled to receive Atezo/Bev. Patients were followed to determine progression-free survival (PFS) and overall survival (OS). Plasma GH levels were measured by ELISA and used to stratify the HCC patients into GH-high and GH-low groups (the cutoff normal GH levels in women and men are ≤3.7 μg/L and ≤0.9 μg/L, respectively). The Kaplan-Meier method was used to calculate median OS and PFS and Log rank test was used to compare survival outcomes between GH-high and -low groups. Thirty-seven patients were included in this analysis, of whom 31 were males and 6 females, with a median age of 67 years (range: 37–80). At the time of the analysis, the one-year survival rate was 70% (95% CI: 0.51, 0.96) among GH low patients and 33% (95% CI: 0.16, 0.67) among GH high patients. OS was significantly superior in GH-low compared to GH-high patients (median OS: 18.9 vs. 9.3 months; p = 0.014). PFS showed a non-significant trend in favor of GH-low patients compared to the GH-high group (median PFS: 6.6 vs. 2.9 months; p = 0.053). “Plasma GH is a biomarker candidate for predicting treatment outcomes in advanced HCC patients treated with Atezo/Bev. This finding should be further validated in larger randomized clinical trials in advanced HCC patients.” DOI: https://doi.org/10.18632/oncotarget.28322 Correspondence to: Ahmed Omar Kaseb - akaseb@mdanderson.org Keywords: growth hormone, hepatocellular carcinoma, immunotherapy, atezolizumab, bevacizumab About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com.

Plasma Growth Hormone in HCC: A Biomarker of Response to Atezo/Bev?

Oncotarget

Play Episode Listen Later Dec 9, 2022 6:09

Listen to a blog summary of a trending research paper published in Volume 13, entitled, “Plasma growth hormone is a potential biomarker of response to atezolizumab and bevacizumab in advanced hepatocellular carcinoma patients.” __________________________________________________ Hepatocellular carcinoma (HCC) is a highly aggressive cancer of the liver with a very poor prognosis; many patients pass away within a year of diagnosis. Currently, there is no effective screening method for HCC and thus, 80% of patients are diagnosed at advanced stages. This makes treatment difficult and often unsuccessful. As a result, new treatments for HCC are constantly being explored. Atezolizumab and bevacizumab are two standard therapies used to treat unresectable, advanced HCC. However, researchers Yehia I. Mohamed, Dan G. Duda, Muhammad O. Awiwi, Sunyoung S. Lee, Lina Altameemi, Lianchun Xiao, Jeffrey S. Morris, Robert A. Wolff, Khaled M. Elsayes, Rikita I. Hatia, Aliya Qayyum, Shadi M. Chamseddine, Asif Rashid, James C. Yao, Armeen Mahvash, Manal M. Hassan, Hesham M. Amin, and Ahmed Omar Kaseb from MD Anderson Cancer Center, Massachusetts General Hospital, Harvard Medical School, Michigan State University, and University of Pennsylvania Perelman School of Medicine noticed a significant gap in research on biomarkers of response in advanced HCC patients treated with atezolizumab plus bevacizumab. The team conducted a new study aimed at beginning to close this gap. On December 6, 2022, their research paper was published in Oncotarget's Volume 13, entitled, “Plasma growth hormone is a potential biomarker of response to atezolizumab and bevacizumab in advanced hepatocellular carcinoma patients.” “This study investigated the biomarker value of plasma growth hormone (GH) level as a potential biomarker to predict outcome in unresectable HCC patients treated with current standard therapy, atezolizumab plus bevacizumab (Atezo/Bev).” Full blog - https://www.oncotarget.org/2022/12/08/plasma-growth-hormone-in-hcc-a-biomarker-of-response-to-atezo-bev/ DOI - https://doi.org/10.18632/oncotarget.28322 Correspondence to - Ahmed Omar Kaseb - akaseb@mdanderson.org Video - https://www.youtube.com/watch?v=r2_6kjhwOfM Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28322 Keywords - growth hormone, hepatocellular carcinoma, immunotherapy, atezolizumab, bevacizumab About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

Bad News For Belantamab-Mafodotin And Atezolizumab's Bladder Cancer Indication

OncoPharm

Play Episode Listen Later Dec 1, 2022 13:54

Recent voluntary withdrawals from the US market of belantamab-mafodotin and atezolizumab's indication for bladder cancer have us weighing (again) the pros & cons of the accelerated approval program. Also, FDA approves the 1st fecal transplant product.

fda bad news indication bladder cancer atezolizumab

Frontline Treatment of Renal Cell Carcinoma

Medscape InDiscussion: Renal Cell Carcinoma

Play Episode Listen Later Sep 1, 2022 20:44

Drs Sumanta Pal and Brian Rini discuss front-line treatment of renal cell carcinoma. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968736). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals. Resources Bevacizumab Plus Interferon-alpha Versus Interferon-alpha Monotherapy in Patients With Metastatic Renal Cell Carcinoma: Results of Overall Survival for CALGB 90206 https://ascopubs.org/doi/10.1200/jco.2009.27.18_suppl.lba5019 An updated table of the front-line IO combination RCC studies that have shown an OS advantage https://twitter.com/brian_rini/status/1309609380585844736/photo/1 Targeting PD-1 or PD-L1 in Metastatic Kidney Cancer: Combination Therapy in the First-Line Setting https://aacrjournals.org/clincancerres/article/26/9/2087/83102/Targeting-PD-1-or-PD-L1-in-Metastatic-Kidney Conditional Survival and Long-term Efficacy With Nivolumab Plus Ipilimumab Versus Sunitinib in Patients With Advanced Renal Cell Carcinoma https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.34180 International Metastatic Renal Cell Carcinoma Database Consortium Criteria https://www.uptodate.com/contents/image?imageKey=ONC%2F116130&topicKey=ONC%2F2984&source=see_link Molecular Correlates Differentiate Response to Atezolizumab (atezo) + Bevacizumab (bev) vs Sunitinib (sun): Results From a Phase III Study (IMmotion151) in Untreated Metastatic Renal Cell Carcinoma (mRCC) https://cslide.ctimeetingtech.com/esmo2018/attendee/confcal/presentation/list?q=LBA31 Nivolumab Versus Everolimus in Patients With Advanced Renal Cell Carcinoma: Updated Results With Long-term Follow-up of the Randomized, Open-Label, Phase 3 CheckMate 025 Trial https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415096/pdf/nihms-1732721.pdf Lenvatinib Plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma https://www.nejm.org/doi/10.1056/NEJMoa2035716 The Uromigos Debate: Treatment of Favorable Risk Renal Cancer https://anchor.fm/the-uromigos/episodes/Episode-67-The-Third-Uromigos-Debate---fPD1VEGF-vs-PD1CTLA4-for-front-line-renal-cancer-emjpji Health-Related Quality-of-Life Outcomes in Patients With Advanced Renal Cell Carcinoma Treated With Lenvatinib Plus Pembrolizumab or Everolimus Versus Sunitinib (CLEAR): A Randomised, Phase 3 Study https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(22)00212-1/fulltext Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (COSMIC-313) https://clinicaltrials.gov/ct2/show/NCT03937219 A Study of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib, Versus Pembrolizumab and Lenvatinib, for Treatment of Advanced Clear Cell Renal Cell Carcinoma (MK-6482-012) https://clinicaltrials.gov/ct2/show/NCT04736706 Twitter poll questions: What magnitude of benefit is required to adopt triplets? OS https://mobile.twitter.com/brian_rini/status/1508450496104783877 What magnitude of absolute PFS benefit vs doublets is required to adopt triplets? https://mobile.twitter.com/brian_rini/status/1508450910506295305 What would be the most convincing endpoint to adopt triplets? https://mobile.twitter.com/brian_rini/status/1508451622564909057 Molecular Subsets in Renal Cancer Determine Outcome to Checkpoint and Angiogenesis Blockade https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436590/ OPtimal Treatment by Invoking biologic Clusters in Renal Cell Carcinoma (OPTIC RCC) https://www.kcameetings.org/wp-content/uploads/2021/12/IKCSNA21_TIP8_Chen.pdf

Adjuvant Treatment With Immunotherapy

Medscape InDiscussion: Renal Cell Carcinoma

Play Episode Listen Later Sep 1, 2022 22:37

Drs Sumanta Pal and Tian Zhang review the state of the data on adjuvant treatment with immunotherapy for patients with renal cell carcinoma, including where current clinical trials stand. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968737). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals. Resources Immunotherapy With Nivolumab and Ipilimumab Followed by Nivolumab or Nivolumab With Cabozantinib for Patients With Advanced Kidney Cancer, The PDIGREE Study https://clinicaltrials.gov/ct2/show/NCT03793166 The Role of Targeted Therapy in the Management of High-Risk Resected Kidney Cancer: What Have We Learned and How Will It Inform Future Adjuvant Trials https://journals.lww.com/journalppo/Abstract/2020/09000/The_Role_of_Targeted_Therapy_in_the_Management_of.3.aspx Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy https://www.nejm.org/doi/10.1056/NEJMoa1611406 Sutent (sunitinib) prescribing information https://labeling.pfizer.com/showlabeling.aspx?id=607 Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma (KEYNOTE-564) https://www.nejm.org/doi/full/10.1056/NEJMoa2106391 RAMPART: A Phase III Multi-arm Multi-stage Trial of Adjuvant Checkpoint Inhibitors in Patients With Resected Primary Renal Cell Carcinoma (RCC) at High or Intermediate Risk of Relapse https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520913/ A Study of Atezolizumab as Adjuvant Therapy in Participants With Renal Cell Carcinoma (RCC) at High Risk of Developing Metastasis Following Nephrectomy (IMmotion010) https://clinicaltrials.gov/ct2/show/NCT03024996 A Comparison of Sunitinib with Cabozantinib, Crizotinib, and Savolitinib for Treatment of Advanced Papillary Renal Cell Carcinoma: a Randomised, Open-Label, Phase 2 Trial https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8687736/ A Study Comparing Nivolumab, Nivolumab in Combination With Ipilimumab and Placebo in Participants With Localized Kidney Cancer Who Underwent Surgery to Remove Part of a Kidney (CheckMate 914) https://clinicaltrials.gov/ct2/show/NCT03138512 PROSPER: Phase III RandOmized Study Comparing PERioperative nivolumab versus observation in patients with renal cell carcinoma (RCC) undergoing nephrectomy (ECOG-ACRIN EA8143). https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.TPS4596 Pembrolizumab as Post Nephrectomy Adjuvant Therapy for Patients With Renal Cell Carcinoma: Results From 30-Month Follow-up of KEYNOTE-564 https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.6_suppl.290 Leibovich RCC Model: Prediction of Progression After Radical Nephrectomy for patients With Clear Cell Renal Cell Carcinoma https://cancernomograms.com/nomograms/972 Effects of Adjuvant Sorafenib and Sunitinib on Cardiac Function in Renal Cell Carcinoma Patients without Overt Metastases: Results From ASSURE, ECOG 2805 https://aacrjournals.org/clincancerres/article/21/18/4048/117759/Effects-of-Adjuvant-Sorafenib-and-Sunitinib-on

Experts Discuss Challenges in Advanced Hepatocellular Carcinoma Management

Clinical Conversations » Podcast Feed

Play Episode Listen Later Aug 22, 2022 26:12

In this podcast episode from Clinical Care Options (CCO), Heinz-Josef Klumpen, MD, PhD, and Chris Verslype, MD, PhD, discuss challenges in selecting and sequencing therapy for patients with advanced hepatocellular carcinoma. Topics include:Factors to consider before selecting frontline immunotherapyRole of TKIs in the frontlineImpact of Child-Pugh status on the efficacy of immunotherapy/VEGF inhibitor combination therapyReal-world evidence on frontline immunotherapy/VEGF combination therapyFactors to consider when selecting second-line therapy including the role of TKIs and planning for multiple lines of therapyPresenters:Heinz-Josef Klumpen, MD, PhDStaff Specialist, Medical OncologistDepartment of Medical OncologyAmsterdam UMCAmsterdam, The NetherlandsChris Verslype, MD, PhDProfessorClinical Digestive OncologyKULeuvenHead of ClinicHepatologyDigestive OncologyU.Z. LeuvenLeuven, Belgium

challenges phd management md belgium factors himalaya stride immunotherapy hcc liver cancer vegf hepatocellular carcinoma tki bevacizumab tkis atezolizumab sorafenib lenvatinib child pugh

Updated Adjuvant Atezolizumab Data (& more)

OncoPharm

Play Episode Listen Later Aug 11, 2022 15:18

New OS data is out for adjuvant atezolizumab in NSCLC - how does it compare to the original DFS data? Plus, lots of recent FDA expanded approvals to discuss.

data fda dfs nsclc adjuvant atezolizumab

Podcast 299: Lung cancer and atezolizumab — results from the IMpower010 trial

Play Episode Listen Later Aug 9, 2022 14:58

A VIDEO RECORDING OF THIS INTERVIEW IS AVAILABLE HERE. Interim results on overall survival in phase 3 of the IMpower010 trial were presented at this year's meeting of the International Assosciation for the Study of Lung Cancer (IASLC). As part of the NEJM Group's coverage of the conference, Christine Sadlowski interviewed the presenter, Dr. Enriqueta Felip. […] The post Podcast 299: Lung cancer and atezolizumab — results from the IMpower010 trial first appeared on Clinical Conversations.

study trial lung interim lung cancer atezolizumab

Expert Insights on New Data From ASCO 2022 Informing Treatment for Endometrial, Ovarian, and Cervical Cancers

Play Episode Listen Later Jun 30, 2022 38:27

In this episode, Jubilee Brown, MD, and Elisabeth Diver, MD, provide expert insights on new data presented at ASCO 2022 for ovarian, endometrial, and cervical cancers regarding:Subgroup analyses from KEYNOTE-826 evaluating pembrolizumab in combination with chemotherapy with or without bevacizumab in persistent, recurrent, or metastatic cervical cancerPreliminary subgroup analyses from phase III ENGOT-EN5/GOG-3055 SIENDO trial of selinexor vs placebo maintenance in recurrent endometrial cancerUpdated analyses from phase I GARNET trial of dostarlimab in dMMR/MSI-H and pMMR/MSS advanced/recurrent endometrial cancer (cohorts A1 and A2)EndoBARR trial of atezolizumab, bevacizumab, and rucaparib in previously treated recurrent and progressive endometrial cancerPhase III ATHENA-MONO trial of first-line rucaparib vs placebo maintenance after platinum-based chemotherapy in patients with advanced ovarian cancerPresenters:Jubilee Brown, MDProfessor and Division DirectorGynecologic OncologyLevine Cancer Institute, Atrium HealthCharlotte, North CarolinaElisabeth Diver, MDClinical Assistant ProfessorDivision of Gynecologic OncologyDepartment of Obstetrics and GynecologyStanford UniversityStanford Cancer InstituteStanford University Hospital and ClinicsStanford, CaliforniaContent supported by educational grants from AstraZeneca, GlaxoSmithKline, Karyopharm Therapeutics, and Merck Sharp & Dohme Corp.Link to full program, including a downloadable highlights slideset, and ClinicalThought commentaries:https://bit.ly/3ufB8Js

Optimizing Immune Checkpoint Inhibitor Therapy in Advanced Non-Small-Cell Lung Cancer

therapy md optimizing immune ici checkpoint immunotherapy inhibitor nsclc pd l1 small cell lung cancer pembrolizumab immune checkpoint inhibitors nivolumab ipilimumab atezolizumab iraes advanced nsclc

Play Episode Listen Later Jun 30, 2022 12:51

In this episode, Sandip Patel, MD shares his thoughts on optimizing immune checkpoint inhibitor (ICI) therapy in advanced non-small-cell lung cancer (NSCLC) and discusses best practices for individualizing therapy decisions and managing adverse events.Topics include:Currently approved ICIsRole of biomarker and PD-L1 testing in advanced NSCLCStrategies to individualize ICI treatment for patients with advanced NSCLCStrategies for identifying and managing immune-related adverse events in patients treated with ICIPresenter:Sandip P. Patel, MDAssociate ProfessorDepartment of MedicineDivision of Hematology/OncologyUniversity of California – San DiegoLa Jolla, California Link to full program:https://bit.ly/39vuCHC

Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer: An Update from ASCO 2022

survival findings msn immunotherapy asco nsclc small cell lung cancer immune checkpoint inhibitors pembrolizumab nivolumab ipilimumab atezolizumab iraes advanced nsclc

Play Episode Listen Later Jun 27, 2022 19:42

In this episode, Beth Sandy, MSN, CRNP provides her thoughts on key data presented at the 2022 ASCO annual conference relating to immune checkpoint inhibitors in non-small cell lung cancer (NSCLC). Findings covered include:Survival results after 3 years from the phase III Checkmate 9LA study of nivolumab and ipilimumab combined with 2 cycles of chemotherapy vs chemotherapy in previously untreated advanced NSCLCUpdated survival and safety results after 5 years from the phase III Checkmate 227 study of nivolumab and ipilimumab vs chemotherapy in previously untreated advanced NSCLC, including assessment of a treatment-free intervalUpdated analysis from the phase III ATEZO-BRAIN trial of atezolizumab + carboplatin and pemetrexed in patients with advanced NSCLC with untreated brain metastases Updated overall response analysis from the phase II KEYNOTE-799 study of pembrolizumab with concurrent chemoradiation in unresectable, locally advanced stage III NSCLCResults from a phase II trial evaluating nivolumab plus ipilimumab vs nivolumab monotherapy following chemoradiation in unresectable stage III NSCLCPathological complete response results from the phase II NADIM II study of nivolumab and chemotherapy vs chemotherapy in the neoadjuvant NSCLC settingPresenter:Beth Sandy, MSN, CRNPNurse PractitionerAbramson Cancer CenterUniversity of PennsylvaniaPhiladelphia, PennsylvaniaLink to full program:https://bit.ly/39vuCHC

NSCLC: efficacia di Atezolizumab nel paziente over 70

DrTalk | Oncology

Play Episode Listen Later Apr 27, 2022 8:03

Lung Pod - condivisione di esperienze cliniche in ambito lung cancerUna rassegna di casi clinici e di esperienze sul campo riguardanti la diagnosi, la gestione e il trattamento delle neoplasie polmonari nel setting real world in questi podcast che vedono protagonisti alcuni dei più importanti esperti italiani.Seguici sui nostri socialInstagram (@drtalk_it)Twitter (@drtalk_it)YouTube (DrTalk_it)

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Anti-TIGIT Therapy: Overview of Current Clinical Evidence and Key Ongoing Trials

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Play Episode Listen Later Apr 15, 2022 22:03

In this episode, Jyoti D. Patel, MD, and Ani Balmanoukian, MD, discuss several studies investigating agents targeting TIGIT, an emerging immune checkpoint target with promising results in PD-L1-positive NSCLC. The episode includes a review of phase II data on the use of tiragolumab plus atezolizumab in NSCLC, the use of PD-L1 as a marker of response, the potential role of anti-TIGIT therapies in solid tumors, and ongoing trials in lung cancer including SKYSCRAPER-01, SKYSCRAPER-02, SKYSCRAPER-03, and SKYSCRAPER-05. Presenters:Jyoti D. Patel, MDProfessor of MedicineDivision of Hematology and OncologyMedical Director for Thoracic OncologyAssistant Director for Clinical ResearchAssociate Vice Chair of Clinical ResearchDepartment of MedicineRobert H. Lurie Comprehensive Cancer CenterNorthwestern UniversityChicago, Illinois Ani Balmanoukian, MDDirector of Thoracic OncologyMedical OncologyThe Angeles Clinic and Research Institute, a Cedars-Sinai AffiliateLos Angeles, CaliforniaLink to the complete program, including an online text module with downloadable slidesets, ClinicalThought commentaries, and an additional podcast on this topic:https://bit.ly/38qVCH7

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Efficacia di Atezolizumab in seconda linea nel paziente fragile

DrTalk | Oncology

Play Episode Listen Later Apr 13, 2022 8:29

HCC: Treatment-Related Adverse Events, Case Discussions and Q&A – Episode 2

Play Episode Listen Later Feb 25, 2022 31:06

In this second episode of two podcasts, Dr. Amit Singal and Dr. Mark Yarchoan discuss how to identify, prevent and mitigate treatment-related adverse events, and review cases with careful considerations for patient-specific factors guiding treatment selection, followed by a question-and-answer session on the management of patients with HCC. This activity is available for CE/CME credit. Claim your credit at pce.is/GIGU.Contributors:Amit Singal, MD, MSMark Yarchoan, MDBridget O'Brien, DNP, FNP-BC, AOCNPDr Singal: consulting fees: AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Exelixis, Genentech, Roche.Dr Yarchoan: consulting fees: AstraZeneca, Eisai, Exelixis, Genentech; other financial or material support: Bristol-Myers Squibb, Incyte.Dr O'Brien: fees for non-CME/CE services: Amgen, Novartis.

HCC: Current State, Available and Emerging Therapies – Episode 1

Play Episode Listen Later Feb 25, 2022 33:04

In this first episode of two podcasts, Dr. Amit Singal and Dr. Mark Yarchoan discuss the latest data supporting their approach to selecting treatment regimens for patients with HCC, with topics including: the current challenges in the management of HCC, recommended initial workup strategies and the evolving treatment landscape in HCC. This activity is available for CE/CME credit. Claim your credit at pce.is/GIGU.Contributors:Amit Singal, MD, MSMark Yarchoan, MDBridget O'Brien, DNP, FNP-BC, AOCNPDr Singal: consulting fees: AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Exelixis, Genentech, Roche.Dr Yarchoan: consulting fees: AstraZeneca, Eisai, Exelixis, Genentech; other financial or material support: Bristol-Myers Squibb, Incyte.Dr O'Brien: fees for non-CME/CE services: Amgen, Novartis.

TKIs for Advanced HCC in the Second Line and Beyond

Play Episode Listen Later Feb 22, 2022 17:14

In this podcast episode from Clinical Care Options (CCO), Josep M. Llovet, MD, PhD, and Markus Peck-Radosavljevic, MD, MBA, discuss second line treatment of patients with advanced hepatocellular carcinoma. Topics include:Available agents for the management of advanced hepatocellular carcinoma in the second lineThe current role of tyrosine kinase inhibitors in second-line treatment of advanced hepatocellular carcinomaOngoing clinical trials in the second-line settingPresenters: Josep M. Llovet, MD, PhD, FAASLDProfessor of MedicineDirector, Mount Sinai Liver Cancer ProgramDivision of Liver DiseasesMount Sinai School of MedicineNew York, New YorkProfessor of ResearchLiver Unit, IDIBAPSHospital Clinic BarcelonaBarcelona, SpainUniv. Prof. Markus Peck-Radosavljevic, MD, MBAProfessor of MedicineMedical University of ViennaVienna, AustriaDepartment Chair, Innere Medizin und GastroenterologieKlinikum Klagenfurt am WörtherseeKlagenfurt am Wörthersee, AustriaLink to full program, including accompanying downloadable slidesets:https://bit.ly/2ZL9bxq

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Advanced Urothelial Cancer: Applying New Therapeutic Options, Part 2

harvard medical school abrams ras colorectal cancer metastatic atezolizumab cabozantinib

Play Episode Listen Later Feb 11, 2022 37:03

In this second of two podcasts, discuss the management of advanced urothelial cancer with novel therapies and how to address adverse events, and concludes the episode with a review of audience questions and patient cases. This activity is available for CE/CME credit. Claim your credit at pce.is/GIGU.Contributors:Arjun Balar, MDRana R. McKay, MDTerran W. Sims, MSN, ACNP-C, CNN-BC, COCNDr Balar: consulting fees: Bristol-Myers Squibb, Incyte, Istari Oncology, Janssen, Pfizer; consulting fees/research support: Immunomedics, Seagen; consulting fees/contracted research/fees for non-CME/CE services: AstraZeneca/Medimmune, Genentech; Merck; consulting fees/contracted research: Immunomedics/Gilead, Nektar, Seagen; consulting/ownership interest: EpiVax Oncology, GT Biopharma.Dr McKay: consulting fees: AstraZeneca, Bristol-Myers Squibb, Calithera, Caris, Dendreon, Exelixis, Janssen, Merck, Myovant, Novarits, Sanofi, Sorrento Therapeutics; Vividion Therapeutics; consulting fees/contracted research: Bayer, Pfizer, Tempus.Ms Sims: consulting fees: Coloplast.

cancer options claim pfizer sims astrazeneca therapeutic msn mckay merck janssen chemotherapy sanofi immunotherapy genentech bristol myers squibb tempus caris nektar gigu pembrolizumab seagen nivolumab ctdna incyte cme/ce coloplast atezolizumab arjun balar dendreon astrazeneca medimmune

Cabozantinib/Atezolizumab for Metastatic Colorectal Cancer: Thomas Abrams, MD

Oncology Data Advisor

Play Episode Listen Later Feb 8, 2022 5:52

In this interview, Dr. Thomas Abrams of Harvard Medical School discusses the role that cabozantinib/atezolizumab may play for patients with metastatic colorectal cancer, particularly those with RAS wild-type disease, in the coming years.

JAMA Oncology : Atezolizumab Plus Bevacizumab vs Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma

JAMA Network

Play Episode Listen Later Dec 23, 2021 22:38

Interview with Robert J. Motzer, MD, author of Final Overall Survival and Molecular Analysis in IMmotion151, a Phase 3 Trial Comparing Atezolizumab Plus Bevacizumab vs Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma. Hosted by Jack West, MD.

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Atezolizumab Plus Bevacizumab vs Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma

JAMA Oncology Author Interviews: Covering research, science, & clinical practice in oncology that improves the care of patien

Play Episode Listen Later Dec 23, 2021 22:38

interview patients md phase metastatic untreated renal cell carcinoma bevacizumab jack west atezolizumab sunitinib robert j motzer

Cancer Topics – Beyond Adjuvant Chemotherapy: Precision Oncology in Early-stage NSCLC

ASCO eLearning Weekly Podcasts

Play Episode Listen Later Dec 15, 2021 31:03

Adjuvant immunotherapy is a game-changer for early lung cancer, but it is not the best choice for every patient. Through patient cases, Drs. Karen Kelly (University of California Davis) and Howard West (City of Hope Cancer Center) explore considerations in shared decision making and personalizing therapy. Subscribe: Apple Podcasts, Google Podcasts | Additional resources: education.asco.org | Contact Us Air Date: 12/15/21

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FDA D.I.S.C.O. Burst Edition: FDA approval of Tecentriq (atezolizumab) for adjuvant treatment following resection and platinum-based chemotherapy in patients with stage II to IIIA non-small cell lung cancer

FDA Drug Information Soundcast in Clinical Oncology (D.I.S.C.O.)

Play Episode Listen Later Oct 26, 2021 4:00

Listen to a soundcast of the October 15, 2021 FDA approval of Tecentriq (atezolizumab) for adjuvant treatment following resection and platinum-based chemotherapy in patients with stage II to IIIA non-small cell lung cancer.

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Withdrawal of Atezolizumab's Indication for Metastatic Triple-Negative Breast Cancer

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Play Episode Listen Later Sep 3, 2021 9:27

This week, we're reviewing the details of Genentech's decision to withdraw atezolizumab's indication for metastatic triple-negative breast cancer. We'll then hear about a systematic review and meta-analysis that provided a profile of treatment-related adverse events observed in clinical trials combining PD-1 or PD-L1 inhibitors with chemotherapy, targeted therapy, immunotherapy, and radiotherapy.Coverage of stories discussed this week on ascopost.com:Update on U.S. Indication for Atezolizumab in PD-L1–Positive Metastatic Triple-Negative Breast CancerProfile of Adverse Events Related to PD-1 and PD-L1 Inhibitor–Based TherapyTo listen to more podcasts from ASCO, visit asco.org/podcasts.

Journal Club 泌尿肾内星期二 Episode 27

Journal Club 前沿医学报导

Play Episode Listen Later Dec 9, 2020 27:40

FDA 批准首个用于治疗晚期尿路上皮癌的FGFR激酶抑制剂Nature Medicine 免疫检查点抑制剂PD-L1联合CTLA-4单抗治疗高危尿路上皮癌前沿医学多功能天然高分子纳米颗粒作为抗纤维化基因载体用于治疗CKD厄达替尼（erdafitinib）我们的节目曾在《消化科星期三 Episode 3》中介绍过培米加替尼，治疗成纤维细胞生长因子受体编码基因（FGFR）基因融合或重排的局部晚期胆管癌，胆管癌中约有20%的患者存在这种基因突变。研究人员发现FGFR突变在尿路上皮癌中也很常见，并且可能与对免疫干预的敏感性降低相关。厄达替尼（erdafitinib）是一种FGFR1-4的酪氨酸激酶抑制剂，2019年4月，FDA已经批准厄达替尼（erdafitinib）用于治疗局部晚期或转移性尿路上皮癌。《BLC2001研究：厄达替尼治疗局部晚期或转移性尿路上皮细胞癌的2期临床研究》New England Journal of Medicine，2019年8月 (1) 在这项开放标签的2期研究中，纳入了FGFR基因突变的、局部晚期和不可切除或转移性尿路上皮细胞癌的患者99人，所有患者既往均接受过化疗，并在化疗12个月内发生疾病进展。最初将患者随机分组，随后根据中期分析，将连续用药方案的起始剂量设定为8mg/d，并可在药效学指导下，将剂量增加至9mg/d。经过平均5个周期的厄达替尼治疗后，缓解率为40%（3%完全缓解，37%部分缓解）。在既往接受过免疫治疗患者中，缓解率为59%。中位无进展生存期为5.5个月，中位总生存期为13.8个月。结论：在既往接受过治疗的、有FGFR基因突变的、且患局部晚期和不可切除或转移性的尿路上皮细胞癌的患者中，厄达替尼治疗后肿瘤客观缓解率达40%。膀胱尿路上皮癌膀胱癌是最常见的泌尿系统恶性肿瘤，其中尿路上皮癌（也称移行细胞癌）是主要的组织学类型，占所有膀胱癌的90%。膀胱尿路上皮癌可表现为非肌肉浸润癌、肌肉浸润癌和转移癌，病变的程度可以反映自然病程，并决定了治疗和预后。膀胱癌通常表现为肉眼血尿或镜下血尿，刺激性或梗阻性排尿困难也可以是首发症状。非肌肉浸润性膀胱癌的治疗对于非肌肉浸润性膀胱癌的患者，采用经尿道膀胱肿瘤切除术（TURBT），并联合膀胱内辅助治疗等保守治疗方式有可能保留膀胱功能。膀胱内辅助治疗主要包括卡介苗（牛结合分支杆菌的减毒活疫苗）和丝裂霉素C、表柔比星、吉西他滨等化疗药物。《系统回顾：膀胱治疗非肌肉浸润性膀胱癌的疗效》European Urology，2020年9月 (2)研究的目的是评价在卡介苗治疗后，保留膀胱功能的患者的疾病完全缓解率和无复发率。研究系统地回顾了42项研究，包括24种治疗方案、2254名患者。包含原位癌在内的肿瘤治疗中位完全缓解率，6个月时为26%，12个月时为17%，24个月时为8%。相比，乳头状癌的平均无进展率，6个月时为67%，12个月时为44%，24个月时为10%。特别是在卡介苗无效的、接受草分枝杆菌细胞壁-核酸复合物的患者中，6个月和12个月的完全缓解率分别为45%和27%；6、12、24个月中位不带病生存率分别为43%、35%和18%。总的中位无进展率为91%，原位癌的研究中为95%，乳头状癌的研究中为89%。膀胱内给药的不良反应少，且轻微。结论：卡介苗治疗后的、保留膀胱疗法，在非肌肉浸润性膀胱癌患者中取得了适度的疗效。《NIMBUS研究：卡介苗标准剂量和数量灌注治疗重度非肌肉浸润性膀胱癌的3期临床研究》European Urology，2020年11月 (3)膀胱内灌注卡介苗治疗是一种被广泛接受的预防非肌肉浸润性膀胱癌复发的策略，但是具有显著的毒性。研究的目的是评估了降低标准剂量卡介苗灌注的次数是否可以达到同样的疗效。研究纳入了345名非肌肉浸润性膀胱癌的患者，分别接受标准治疗（诱导6周，在第3、6和12个月时各治疗3周，共15次灌注），或低频率治疗（第1、2和6周诱导，在第3、6和12个月时各治疗2周，共9次灌注）。中位随访12个月后，标准治疗组复发率12%，低频率治疗组复发率27%。安全性分析达到了预先定义的、无效停止标准。结论：在预防膀胱癌复发方面，标准治疗方案更好，目前研究已经停止对参与者的招募。《国家质量指标项目：提高非肌肉浸润性膀胱癌经尿道膀胱肿瘤切除术的质量和有效性》European Urology，2020年8月 (4)非肌肉浸润性膀胱癌的临床预后部分取决于初始干预。为了改善和标准化癌症治疗，苏格兰实施了一项针对膀胱癌的国家质量指标项目。研究中纳入了2689例患者，标准干预包括：（1）使用膀胱图；（2）经尿道膀胱肿瘤切除术后单次膀胱内灌注丝裂霉素C一次；（3）逼尿肌活检；（4）高危膀胱癌患者中，早期行二次手术。研究中，67%患者接受了术后一次膀胱灌注；复发率、残余癌比例和继发肿瘤的比例分别为13%、33%和2.9%。术后一次膀胱灌注复发率降低相关；逼尿肌活检则癌症残留的可能性减半。结论：在苏格兰实施国家质量指标计划似乎有助于向患者提供高质量的经尿道膀胱肿瘤切除术，且降低了术后的复发率、肿瘤分期更准确。《DaBlaCa-13研究：短期强化化疗与标准辅助膀胱内灌注治疗非肌肉浸润性膀胱癌》European Urology，2020年8月 (5)膀胱灌注治疗非肌肉浸润性膀胱癌可减少复发。术前灌注化疗副作用更少，甚至一些患者在治疗后都无需接受肿瘤切除术了。研究旨在比较术前丝裂霉素C短期强化化疗治疗复发性非肌肉浸润性膀胱癌的效果。研究纳入120例患者，短期强化化疗组，膀胱灌注化疗每周3次，共2周；对照组先行经尿道膀胱肿瘤切除术，术后6周每周进行一次膀胱灌注辅助治疗。在短期强化化疗组中，有33名参与者（57%）出现了肿瘤完全缓解，且不良事件少。结论：术前短期强化化疗使一半以上的患者避免肿瘤切除术，但长期疗效仍需随访观察。肌肉浸润性膀胱癌的治疗对于肌肉浸润性膀胱癌，需行根治性膀胱切除术+尿流改道术，以及辅助化疗、免疫治疗。化疗方案中的MVAC方案（甲氨蝶呤、长春碱、多柔比星、顺铂）被认为是一线化疗方案，临床实践中多在这个方案上增减。目前已有几个免疫检查点抑制剂被获批用于膀胱尿路上皮癌的治疗：阿替利珠单抗（atezolizumab），帕博利珠单抗（pembrolizumab），纳武利尤单抗（nivolumab），阿伟鲁单抗（avelumab），德瓦鲁单抗（durvalumab）。《回顾性综述：FGFR3的水平变化与膀胱癌对铂化疗的敏感性有关》European Urology，2020年8月(6)大约15%的膀胱癌存在成纤维细胞生长因子受体3 （FGFR3）基因突变。研究人员回顾性的比较和综述三个队列的患者：（1）新辅助化疗治疗肌肉侵袭性膀胱癌患者的数据；（2）一线铂类化疗治疗转移性尿路上皮癌患者的数据；（3）来自癌症基因组图谱中的肌肉侵袭性膀胱癌患者的数据。队列一：72例新辅助化疗的肌肉侵袭性膀胱炎癌患者中有13%具有FGFR3突变，均没有达到病理完全缓解，且无复发生存期短。队列三：来自癌症基因组图谱中的肌肉侵袭性膀胱癌的患者，接受辅助化疗、且伴有FGFR3突变的无复发生存期也更短。相反，在未接受化疗的患者中，FGFR3突变与无复发生存期更长、总生存率更高。队列二：转移性尿路上皮癌的患者中，FGFR3突变虽然药物反应低，但不影响无进展生存率和总生存率。结论：肌肉浸润性膀胱癌中，FGFR3突变可能与围手术期铂类药物化疗反应差、易复发有关。《IMvigor130研究：化疗联合阿替利珠单抗治疗转移性尿路上皮癌的3期临床研究》Lancet，2020年5月 (7)这个多中心、3期、随机研究的目的是，比较阿替利珠单抗与安慰剂加铂类化疗在一线转移性尿路上皮癌的疗效。研究纳入未经治疗的、≥18岁的、局部晚期或转移性尿路上皮细胞癌患者共1213人。随机接受阿替利珠单抗+铂类化疗，或阿替利珠单抗单药治疗，或安慰剂+铂类化疗，随访11.8个月。中位无进展生存期，在阿替利珠单抗联合化疗组为8·2个月，在安慰剂联合化疗组为6.3个月（p = 0·007）。中位生存期，在阿替利珠单抗联合化疗组为16·0个月，安慰剂联合化疗组为13·4个月（p = 0·027）。阿替利珠单抗单药治疗组中位总生存期为15·7个月，与安慰剂联合化疗组无差异。结论：阿替利珠单抗联合铂类化疗延长了转移性尿路上皮癌患者的无进展生存，研究支持使用阿替利珠单抗联合铂类化疗作为转移性尿路上皮癌的潜在的、一线治疗选择。《JAVELIN Bladder200研究：PD-L1单抗阿伟鲁单抗维持治疗局部晚期、或转移性尿路上皮癌》New England Journal of Medicine，2020年9月 (8)这项3期临床试验中，研究人员纳入无法手术的局部晚期、或转移性尿路上皮癌患者共700人，在接受一线化疗后，随机给予阿伟鲁单抗维持治疗、或仅给予支持治疗。阿伟鲁单抗维持治疗能显著延长了患者的总生存期。阿伟鲁单抗组和对照组的，1年总生存率分别为71.3%和58.4%，中位总生存期分别为21.4个月和14.3个月（死亡风险比 0.69，P = 0.001）。阿伟鲁单抗也显著延长了PD-L1阳性的患者的总生存率，两组分别为79.1%和60.4%（风险比 0.56，P < 0.001）。在总体人群中，阿伟鲁单抗组的中位无进展生存期为3.7个月，对照组为2.0个月（疾病进展或死亡的风险比为0.62）；在PD-L1阳性的人群中，阿伟鲁单抗组的中位无进展生存期为5.7个月，对照组为2.1个月（风险比 0.56）。结论：一线化疗+阿伟鲁单抗维持治疗，能进一步延长了患者的总生存期。《随机对照研究：卡博替尼和纳武利尤单抗联合或不联合伊匹木单抗治疗转移性尿路上皮癌的1期临床研究》Journal of Clinical Oncology，2020年10月 (9)卡博替尼（cabozantinib）是一种酪氨酸激酶受体抑制剂，纳武利尤单抗（nivolumab）是一种PD-1单抗，伊匹木单抗（ipilimumab）是一种CTLA-4单抗。研究的目的是评估了卡博替尼联合纳武利尤单抗的CaboNivo方案，以及CaboNivo联合伊匹木单抗的CaboNivoIpi方案在转移性尿路上皮癌和其他泌尿生殖系统恶性肿瘤患者中的安全性和有效性，共入组54人。平均随访时间为44.6个月，转移性尿路上皮癌的客观缓解率为38.5%，平均缓解持续时间尚未达到，中位无进展生存期达12.8个月，中位总生存期为25.4个月。CaboNivo和CaboNivoIpi治疗组中，严重不良事件发生率分别为75%和87%，主要包括疲劳、腹泻、高血压、肝炎、结肠炎。II期临床研究推荐剂量为卡博替尼40 mg/d、纳武利尤单抗3 mg/kg，伊匹木单抗1 mg/kg。结论：CaboNivo方案（卡博替尼+纳武利尤单抗）和CaboNivoIpi（卡博替尼+纳武利尤单抗+伊匹木单抗）方案均显示了良好的耐受性和持久的疗效，多项II期和III期临床研究正在进行中。《随机对照临床研究：新辅助PD-L1加CTLA-4阻滞治疗顺铂化疗无法耐受的、可手术切除的、高危、尿路上皮癌的1期临床研究》Nature Medicine，2020年10月 (10)这是首个抗PD-L1单抗（德瓦鲁单抗，durvalumab）联合抗CTLA-4单抗（曲美木单抗，tremelimumab）。研究纳入在顺铂化疗无法耐受的、具有高危特征的、尿路上皮癌患者共28人（高危特征为肿块大、组织学变异、淋巴血管侵犯、肾盂积水和/或高度上尿路疾病）。在完成手术的患者中，病理完全缓解为37.5%，58%的患者达到无残余侵袭性占位。21%的患者出现免疫相关不良事件，包括无症状实验室异常、肝炎和结肠炎结论：研究提供了抗PD-L1单抗联合抗CTLA-4单抗新辅助治疗的初步安全性、有效性和生物标志物数据，这对于局限性尿路上皮癌患者，特别是具有高危特征且目前没有建立标准护理新辅助治疗的顺铂不合格患者，值得进一步发展。《NABUCCO研究：术前CTLA-4联合PD-1抑制剂治疗局部晚期尿路上皮癌的1期临床研究》Nature Medicine，2020年10月 (11)伊匹木单抗（ipilimumab）是一种CTLA-4单抗，纳武利尤单抗（nivolumab）是一种PD-1单抗，在NABUCCO研究中，纳入了24名III期、尿路上皮癌患者，术前接受两次伊匹木单抗联合纳武利尤单抗治疗后，然后在12周内接受手术切除。研究中46%的患者达到病理学完全缓解，58%达到无残余侵袭性占位。与单独使用PD-1/PD-L1抑制剂的研究相比，伊匹木单抗联合纳武利尤单抗的疗效与基线时CD8+ T细胞活性无关。3-4级免疫相关不良事件发生率分别为55%和41%。结论：在局部晚期尿路上皮癌患者中，CTLA-4联合PD-1阻断可能提供一个有效的术前治疗策略，而不用考虑先前的CD8+ T细胞的活性。纳米颗粒作为抗纤维化基因载体治疗CKD《基础研究：多功能天然高分子纳米颗粒作为抗纤维化基因载体用于治疗慢性肾脏病》J American Society of Nephrology，2020年8月 (12)预防或逆转促纤维化的细胞的基因表型是治疗慢性肾脏病的一个方向，来自南开大学的研究人员开发了一种纳米颗粒，作为抗纤维化的基因的载体，为损伤组织和常驻细胞提供抗纤维化治疗，以限制促纤维化表型的表现。研究人员将表达骨形态发生蛋白7（BMP7）或肝细胞生长因子（HGF）-NK1（HGF/NK1）的质粒DNA包裹在有一层透明质酸壳的聚糖纳米颗粒内，安全地将含有质粒DNA的多功能纳米粒导入肾脏，用于抗纤维化因子的局部和持续表达。在小鼠模型中，静脉注射后，这些纳米颗粒约有10-45%的基因被肾脏摄取，减轻了纤维化的发展，并挽救了肾功能。BMP7基因逆转了纤维化进展、促进肾小管再生；HGF/NK1基因减少胶原纤维沉积。结论：纳米颗粒作为BMP7基因和HGF-NK1基因的载体，提供了今后靶向基因治疗慢性肾脏病的基础。参考文献1.Loriot Y, Necchi A, Park SH, Garcia-Donas J, Huddart R, Burgess E, et al. Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma. New England Journal of Medicine. 2019;381(4):338-48.2.Li R, Sundi D, Zhang J, Kim Y, Sylvester RJ, Spiess PE, et al. Systematic Review of the Therapeutic Efficacy of Bladder-preserving Treatments for Non-muscle-invasive Bladder Cancer Following Intravesical Bacillus Calmette-Guerin. Eur Urol. 2020;78(3):387-99.3.Grimm MO, van der Heijden AG, Colombel M, Muilwijk T, Martinez-Pineiro L, Babjuk MM, et al. Treatment of High-grade Non-muscle-invasive Bladder Carcinoma by Standard Number and Dose of BCG Instillations Versus Reduced Number and Standard Dose of BCG Instillations: Results of the European Association of Urology Research Foundation Randomised Phase III Clinical Trial "NIMBUS". Eur Urol. 2020;78(5):690-8.4.Mariappan P, Johnston A, Padovani L, Clark E, Trail M, Hamid S, et al. Enhanced Quality and Effectiveness of Transurethral Resection of Bladder Tumour in Non-muscle-invasive Bladder Cancer: A Multicentre Real-world Experience from Scotland's Quality Performance Indicators Programme. Eur Urol. 2020.5.Lindgren MS, Bue P, Azawi N, Blichert-Refsgaard L, Sundelin MO, Dyrskjøt L, et al. The DaBlaCa-13 Study: Short-term, Intensive Chemoresection Versus Standard Adjuvant Intravesical Instillations in Non-muscle-invasive Bladder Cancer-A Randomised Controlled Trial. Eur Urol. 2020.6.Teo MY, Mota JM, Whiting KA, Li HA, Funt SA, Lee CH, et al. Fibroblast Growth Factor Receptor 3 Alteration Status is Associated with Differential Sensitivity to Platinum-based Chemotherapy in Locally Advanced and Metastatic Urothelial Carcinoma. Eur Urol. 2020.7.Galsky MD, Arija JÁ A, Bamias A, Davis ID, De Santis M, Kikuchi E, et al. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2020;395(10236):1547-57.8.Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, et al. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020;383(13):1218-30.9.Apolo AB, Nadal R, Girardi DM, Niglio SA, Ley L, Cordes LM, et al. Phase I Study of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced or Metastatic Urothelial Carcinoma and Other Genitourinary Tumors. J Clin Oncol. 2020;38(31):3672-84.10.Gao J, Navai N, Alhalabi O, Siefker-Radtke A, Campbell MT, Tidwell RS, et al. Neoadjuvant PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable high-risk urothelial carcinoma. Nat Med. 2020.11.van Dijk N, Gil-Jimenez A, Silina K, Hendricksen K, Smit LA, de Feijter JM, et al. Preoperative ipilimumab plus nivolumab in locoregionally advanced urothelial cancer: the NABUCCO trial. Nat Med. 2020.12.Midgley AC, Wei Y, Zhu D, Gao F, Yan H, Khalique A, et al. Multifunctional Natural Polymer Nanoparticles as Antifibrotic Gene Carriers for CKD Therapy. J Am Soc Nephrol. 2020.

First-Line Atezolizumab vs Chemotherapy for PD-L1–Positive Metastatic NSCLC

positive coverage outcomes chemotherapy asco first line metastatic nsclc pd l1 atezolizumab

Play Episode Listen Later Oct 16, 2020 12:58

This week, we'll review results of a trial that evaluated first-line anti–PD-L1 therapy vs platinum-based chemotherapy in patients with metastatic lung cancer and high PD-L1 expression. We'll also discuss findings from a study that evaluated whether patients receiving care for advanced cancer based on the recommendations of a molecular tumor board tended to survive longer or experience more time without disease progression.Coverage of stories discussed this week on ascopost.com:First-Line Atezolizumab vs Chemotherapy in PD-L1–Positive Metastatic NSCLC: IMpower110Cancer Therapy Based on Molecular Tumor Board Recommendations: Improvement in Outcomes?To listen to more podcasts from ASCO, visit asco.org/podcasts.

Reports From the ESMO Asia Congress 2019

chinese congress fda reports coverage combination esmo bevacizumab atezolizumab

Play Episode Listen Later Nov 27, 2019 6:45

This week, we summarize two studies presented at the recent ESMO Asia Congress—one on a novel combination therapy for unresectable liver cancer, and the second on the activity of a Chinese-manufactured trastuzumab biosimilar. We'll also discuss last week's FDA approval of acalabrutinib for chronic lymphocytic leukemia or small lymphocytic lymphoma.Coverage of stories discussed this week on ascopost.com:ESMO Asia 2019: Combination of Atezolizumab and Bevacizumab for Unresectable Hepatocellular CarcinomaESMO Asia 2019: Trastuzumab Biosimilar HLX02 Shows Activity in HER2-Positive Metastatic Breast CancerFDA Approves Acalabrutinib for CLL/SLL as Part of Project Orbis

News in Genitourinary Cancers From ESMO 2019