2023 Research Round Up: Gynecologic Cancers, Multiple Myeloma, and Head and Neck Cancers

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The theme of the 2023 ASCO Annual Meeting was “Partnering With Patients: The Cornerstone of Cancer Care and Research.” From June 2 to 6 in Chicago, Illinois, and online, cancer researchers and clinicians from around the world gathered to discuss the latest cancer research and how to ensure that all people receive the cancer care they need. In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field presented at the meeting and explain what it means for people with cancer. In today’s episode, our guests will discuss new research in gynecologic cancers [2:06], multiple myeloma [9:15], and head and neck cancer [16:03]. First, Dr. Lan Coffman discusses new research in ovarian cancer, uterine cancer, and cervical cancer. Dr. Coffman is a physician-scientist and gynecologic oncologist at the Magee-Womens Research Institute and Foundation, and assistant professor in Hematology-Oncology at the University of Pittsburgh School of Medicine. She is also the 2023 Cancer.Net Associate Editor for Gynecologic Cancers. You can view Dr. Coffman’s disclosures at Cancer.Net. Dr. Coffman: Hi, my name is Lan Coffman. I'm a physician-scientist at the University of Pittsburgh. I'm a medical oncologist that specializes in gynecologic cancers, and I'm happy to discuss research that was presented on gynecologic cancers at the 2023 ASCO Annual Meeting. I do have a relevant disclosure. I participated in one of the trials I'm going to discuss, a trial called MIRASOL. I was the site principal investigator at University of Pittsburgh. I think there were a lot of interesting studies to highlight, and I wanted to focus on studies involving ovary cancer, endometrial cancer, and cervix cancers as the main sites that we study in the gynecologic oncology world. So when we talk about ovary cancer, I think there was one really impactful study that was presented at ASCO this year, and it was called MIRASOL. And again, this is the study that I also participated in at our hospital at University of Pittsburgh. So it was a large study, so a randomized phase 3 study looking at a drug called mirvetuximab, which is an antibody-drug conjugate. So basically, it's an antibody against a protein that is expressed on ovarian cancer cells and the protein’s called folate receptor-alpha. And that antibody basically carries a little poison. And so it's kind of like a Trojan horse. This antibody goes, finds that protein on the tumor cells, and then delivers that poison. And so this drug has been studied and actually was presented last year in a different trial called SORAYA, which showed that it had activity, meaning the drug helped to kill ovarian cancer cells, and actually led to the first approval of this drug in ovary cancer. So this trial was the confirmatory trial, so enrolling more patients to see, actually, is it better than standard-of-care chemotherapy? So this was in women with ovarian cancer that had come back and was platinum resistant, meaning the cancer started to grow within 6 months from the last platinum-based therapy. Women were eligible if they had high expression of this folate receptor-alpha, and they had to have a couple of prior lines of therapy. And then they were randomized, so kind of chosen out of a hat to either be treated with mirvetuximab or with investigator's choice chemotherapy. So one of the chemotherapies we'd use standardly. And so that would be something like taxol, or liposomal doxorubicin, or topotecan. And basically, this study was comparing how well does mirvetuximab work compared to chemotherapy. And importantly, it showed that it improved survival, both progression-free survival, so how long it took before the disease started to grow again, but probably more importantly, actually improved overall survival, so how long a woman lived. And actually changed overall survival from about 16 and a half months compared to 12 months with chemotherapy. And so this was really important and demonstrated that mirvetuximab does actually impact women with ovarian cancer and actually helps women live longer. And that's really hard to do in this setting. And the other nice thing about this trial was that not only did it work well, but there are actually lower side effects with it, and so less women actually had to discontinue their treatment, and they had less what we call adverse events, or basically bad things that had happened from the treatment themselves. So just telling us that this drug is actually well tolerated. Women feel well on it, even when their cancer is shrinking. So I think that was one of the most impactful studies in ovary cancer. Moving on to endometrial cancer. We recently had 2 studies, one called RUBY and one called GY018 that looked at using immunotherapy in combination with chemotherapy in endometrial cancer. And what was presented at ASCO was some follow-up from this RUBY trial, which was basically validating that this combination of adding immunotherapy actually helped. To give you a background, traditionally, women that have endometrial cancer that is advanced staged, meaning spread outside of the uterus itself or has come back, we treat it with chemotherapy. But this study added an immunotherapy called dostarlimab in combination with our standard chemotherapy and actually showed that women were living longer with this, at least in that progression-free survival. We're still waiting on final evaluation. But at ASCO, what they reported was another independent blinded review of the data to show that even when we're really carefully looking at this data, it looks like immunotherapy helps women with endometrial cancer live longer. They also presented quality-of-life data showing that women actually feel better with the addition of the immunotherapy. So I think this is practice changing. And again, this data has been coming out over the last year or so, but I do think this will change the way in which endometrial cancer is treated. And then the final thing I wanted to discuss would be in cervix cancer. And while there wasn't a lot of new data presented here in terms of kind of paradigm shifts or large changes, we did have final survival [data] from the KEYNOTE-826 presented, which is also using immunotherapy along with chemotherapy in cervix cancer. And so this was in women that, again, had advanced-stage cervix cancer. So it was a cervix cancer that had moved beyond the cervix itself or cervix cancer that had come back and was treated with chemotherapy along with another immunotherapy called pembrolizumab. And this was the final survival data that confirmed that the immunotherapy did help women live longer. The survival data was impressive with about a 10-month improvement in overall survival. So how long a woman lived. And so that was really confirmatory of the previous trials. So again, that emphasizes that immunotherapy is moved towards the standard of care in cervix cancer as well. I can't hit all the highlights of the impressive research coming out of ASCO 2023, this is a brief summary of some of the critical studies in gynecologic cancers. ASCO: Thank you, Dr. Coffman. Next, Dr. Sagar Lonial discusses new research in multiple myeloma. Dr. Lonial is a professor of Hematology and Medical Oncology at Winship Cancer Institute at Emory University, where he also serves as Department Chair. He is also the 2023 Cancer.Net Associate Editor for Myeloma. You can view Dr. Lonial’s disclosures at Cancer.Net. Dr. Lonial: Hello, I'm Dr. Sagar Lonial from the Emory School of Medicine and the Winship Cancer Institute in Atlanta, Georgia. And today I'm going to discuss some of the really exciting research in the context of multiple myeloma that was presented at the 2023 ASCO Annual Meeting. In terms of my conflicts of interest, I have enrolled patients on many CAR T trials as well as bispecific trials from all of the different companies involved here. So, I do have some engagement with those trials. And one of the studies that I may talk about at the end came from our institution. So I was an investigator on that study as well. When I think about some of the really exciting work that was presented at ASCO this year, there are really 2 big categories of trials that I think were most exciting. And the first is CAR T-cells and moving them earlier and earlier in the disease state. And what we saw at ASCO this year was the CARTITUDE-4 study, which was a randomized phase 3 trial comparing CAR T-cells versus standard treatment in the context of first or second relapsed multiple myeloma. And this was a really important study for us to hear because we know that CAR T-cells are highly effective in the later lines of therapy. A big question at this point is, "Does their efficacy hold up in earlier lines of therapy? And how does it compare in a randomized setting against what we might normally use in that clinical context?" And what I think we were really excited to see at ASCO this year was that CAR T-cells appear to be superior to standard treatment in the context of that randomized phase 3 trial. Now, there were a few patients who were randomized to CAR T-cells who didn't get to the CAR T-cell infusion because their disease progressed in that interval. And that is a challenge that many of us deal with on a regular basis when we think about using a CAR T in a patient. But in general, the treatment was available for almost all patients. And the analysis of benefit as measured by a longer remission duration for the patients who received CAR T cells versus those who didn't was really done on what we call an intent to treat basis. And what that means is if you were randomized to the CAR T arm, even if you didn't get the CAR T, which again was a very small number of patients, you were still evaluated as if you got a CAR. And what I think that tells us is that even taking into account some of those patients who may not get there, there still was significant clinical benefit. And this is really important data for us to have insight into. We've seen this with cilta-cel in CARTITUDE-4. We'd seen similar kinds of findings in KarMMa using ide-cel as the CAR T-cell, although it does appear that the remission duration, at least when you're comparing across trials, appears to be a little bit longer for cilta-cel than what we've seen with ide-cel. But nonetheless, it suggests that even in the context of early relapse, there may be some benefit for CARs over standard therapy. Now, does this mean that CARs are going to replace standard therapy in terms of early relapse? I don't think we know the answer to that right now. I think there's a lot of information that we need to look at to really feel comfortable making that step. The other big set of data I think that we were all very excited about to see at ASCO this year were the T-cell engagers or the bispecifics. And what we saw from a number of different bispecifics was that the efficacy data looks like it continues to hold up. But what to me was really quite exciting was the idea that the T-cell engager could be highly effective even if a patient had seen prior BCMA-directed therapy. And what this means to me is that perhaps if you're progressing on a CAR T-cell, you still may have a pretty reasonable chance at a response, again, to a BCMA-directed therapy with a bispecific. The other way around may not necessarily be the same. And so I think what we learned at this meeting is that the bispecific or T-cell engagers clearly could have activity in the context of prior BCMA-exposed therapy. And I think, as a field, we need to think more about how we define what it means to be resistant to a BCMA-directed therapy. So that I think was really important and exciting and will have relevance in our daily clinical practice. We also saw updates on a different non-BCMA-directed target. So we saw updates on GPRC5D-targeted bispecifics, also known as talquetamab. What I think was really exciting here is we saw a very high overall response rate, modest infectious complications compared to what we've seen with BCMA-directed therapy.   Finally, what I want to wrap up with was a very small study addressing what I think is a pretty significant unmet medical need. And that was a trial from Dr. Nooka at my institution, where we evaluated a combination of carfilzomib with pomalidomide and dexamethasone, or KPD. And we used that specifically as maintenance in the high-risk group. And what we learned from that evaluation is that it appears for patients with high-risk disease that KPD maintenance is better than either carfilzomib and len [lenalidomide] or even bortezomib and lenalidomide, which historically has been what we're using. But there remains an unmet medical need patient population, particularly the double-hit patient population, that even with KPD still didn't have a great outcome overall. So more work for us to do down the road. But certainly, food for thought for many of those other patients that perhaps don't fit into that double-hit classic category. So I think what I've given you is a nice sort of overview of many of the exciting data that were presented at ASCO 2023. Again, go to the website to see additional ones. And thank you again for listening to this brief summary of research in myeloma updates from the 2023 ASCO Annual Meeting. ASCO: Thank you, Dr. Lonial. Finally, Dr. Cristina Rodriguez discusses new research in treating head and neck cancer. Dr. Rodriguez is a medical oncologist at Seattle Cancer Care Alliance, an Associate Professor in the Division of Medical Oncology at the University of Washington, and an Associate Member for solid tumor clinical research at the Fred Hutchinson Cancer Research Center. She is also the 2023 Cancer.Net Associate Editor for Head and Neck Cancers. You can view Dr. Rodriguez’s disclosures at Cancer.Net. Dr. Rodriguez: Hello, my name is Cristina Rodriguez, and today I'm going to discuss some new research focusing on head and neck cancer that was presented at our annual ASCO 2023 meeting. As part of my disclosures, my institution receives research funding from CGEN. My takeaway from this meeting was there were a few major themes represented by the research. One of them was research on uncommon cancer types, such as nasopharyngeal cancer and salivary gland cancer. The other major theme and what was exciting for me was research on groups that were typically not represented in clinical trials in head and neck cancer. These include elderly or frail patients with many other comorbid illnesses that might have excluded them from clinical trials. Another theme was research in areas outside the developed world. In other words, resource-restricted countries. There was some exciting research coming out of that. And finally, a few new agents, novel agents that looked to have activity in patients with head and neck cancer that are going to be studied further. So with that, I'm going to start with talking about research that came out of France, presented by Dr. Fayette. This was a clinical trial that focused primarily on the frail elderly population. A group that might make very difficult for one to enter clinical trial because of many different illnesses or not being fit enough. And this group, out of France, looked at a combination of immunotherapy and a gentler lower dose chemotherapy called carboplatin and paclitaxel. Interestingly, in this group, there was very encouraging results, including 71% of patients having an objective response or a reduction in the size of their tumor, and very few patients, less than 5% of patients, having toxicity that required permanent discontinuation of the drug. So I thought this study was particularly interesting and gives us physicians and patients who are in this situation some more options to use when we're in the treatment of head and neck cancer. The next study that I thought was particularly interesting came out of India and was presented by Dr. Kothari. The special thing about this study was that it asked the question of the efficacy of a very low-cost combination for patients with recurrent or metastatic head and neck cancer. It's a combination that we don't tend to use here in the United States, one that involves methotrexate, celecoxib, and erlotinib. This particular clinical trial was carried out in several sites in India, and it randomized patients to this low-cost oral regimen versus physician's choice. In other words, any type of treatment that might involve immunotherapy or antibody therapy. The main issue here being that sometimes many of these therapies are not easily accessible to patients in low-resourced situations. The investigators observed an overall survival advantage, what that means is more patients lived longer when they use the low-cost oral regimen, which was much more practical, much easier for patients to take, and had more success in improving and prolonging the lives of patients. So I thought that that was a particularly important observation. And we forget a lot of times when we're practicing in the United States that a lot of our practice patterns here may not be applicable to low-resource settings. And I think it's very exciting that research is being carried out to answer questions that are relevant to this area. The third abstract that I thought was particularly intriguing was one presented by Dr. Glenn Hanna from Dana-Farber. And it looked at a new drug called BCA101. BCA101 is an antibody that has 2 functions. It inhibits EGFR, or epidermal growth factor receptor, very commonly overexpressed in head and neck squamous cell carcinomas. And it has a dual function, which is it modulates TGFβ, which is an immunosuppressive cytokine within tumor cells. This drug was combined with pembrolizumab in this small study and offered to patients who have never received treatment for recurrent or metastatic head and neck cancer. There was a lot of enthusiasm for this drug because in the 33 patients enrolled in the trial, 48% of them had an objective response, meaning a reduction in the size of their tumor. Anemia was one of the more common side effects that were noted. But the efficacy of this agent in this population, these patients expressed PD-L1 or had a CPS score of 1, was enough to support further study of this drug and a larger clinical trial is going to be carried out looking to see if this drug will have similar efficacy or better efficacy in a larger population. Finally, the last abstract is one that was presented by Dr. Swiecicki. And it was an interesting abstract to me because it examined the activity of another novel agent not FDA-approved for head and neck cancer, called enfortumab vedotin. This is a class of drugs that belong to a group called antibody-drug conjugates. This is an antibody that's directed toward the target called Nectin-4 and has a small chemotherapy payload that's attached to the antibody. Unlike Dr. Hanna's study, this study was a small phase 2 trial that focused on patients who've previously been treated in the recurrent or metastatic setting and are now receiving this drug either as their second or third option after they developed recurrent or metastatic disease. 46 patients were enrolled in this trial, and 24% of patients had an objective response or reduction in the size of this tumor. Although that number doesn't seem very high, it is an encouraging signal because in patients who previously received treatment for head and neck cancer, we tend to see very poor response rates. So this is encouraging given the population that was studied. Another 32% of these patients had what's called stable disease or no significant change in the size of their tumor. So that too is quite encouraging. This drug is going to also move on for further study in head and neck cancer. So I thought that these themes really brought about a lot of excitement for me for the future of treatments in patients with head and neck cancer, not only in developed countries but also in resource-restricted environments. And I look forward to next year and more work being done in these areas. And I'd like to thank you for listening to this brief summary of developments and head and neck cancer presented in the 2023 ASCO Annual Meeting. ASCO: Thank you, Dr. Rodriguez. 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. 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