Since 1990, the mission of MOASC is to ensure access to quality and affordable care for cancer patients. MOASC represents more than 650 hematologists/oncologists throughout Southern California and strives for ongoing success in ensuring the continued practice of oncology care regardless of the setting, thereby ensuring greater access to oncology care for patients.
By. Anusha Kalbasi, MD
In a recent discussion on adoptive T cell therapies for solid tumors, Anusha Kalbasi, MD, provided a comprehensive analysis of various modalities, shedding light on their challenges and potential breakthroughs. Kalbasi began by delving into the realm of tilt therapy, a longstanding approach for melanoma patients. Over the last decade or two, industry interest has surged, revealing response rates of 30 to 50 percent in heavily pretreated melanoma patients. The comparison with immune checkpoint blockade, particularly ipilimumab, has demonstrated promising data on tilt therapy's longer progression-free survival.
The conversation then shifted to TCR-engineered therapy, where Kalbasi elucidated on the exciting results observed in sarcoma patients, specifically those with synovial sarcoma expressing mage a four. The tangible progress in this field, highlighted by an FDA application, marks a significant step forward in TCR-based therapies, with the potential for expanding to other targets and HLA types.
Moving to CAR T cell therapy for central nervous system (CNS) tumors, Kalbasi, MD, acknowledged the historic success in hematologic cancers and emerging victories in solid tumors. Notably, CAR T cells targeting IL 13 receptor alpha 2 and GD2 showcased early success in glioblastoma and midline glioma, respectively, indicating a shift in the narrative for solid tumor treatments.
Addressing challenges and recent setbacks in TIL, TCR, and CAR therapies, Kalbasi, MD, underscored the shared hurdles of intense conditioning regimens, toxicities, and concerns about on-target effects. Despite these challenges, ongoing strategies in T cell engineering, patient selection, and optimization seek to enhance the therapeutic window for these cell therapies.
The discussion concluded with a glimpse into innovative approaches such as remote-controlled CAR T cells and logic-based CAR T cells. Kalbasi, MD, explained how these cutting-edge techniques leverage synthetic biology to modulate cell function post-administration, offering potential avenues to minimize toxicity and improve efficacy. The logical gating of antigen recognition further addresses the perennial challenge of identifying suitable tumor antigens in CAR T cell therapy, showcasing the evolving landscape of adoptive T cell therapies.
By. Bridget Keenan, MD
Bridget Keenan, MD, discusses the tumor microenvironment (TME) and its crucial role in cancer immunotherapy responses. Dr. Keenan notes that effector T cells align with positive outcomes, while suppressive myeloid cells and cytokine signals within the TME often signify a less favorable prognosis and resistance to immunotherapy.
During the presentation, Dr. Keenan explores targeting the TME through immunotherapies, focusing on tumor metabolism and immunosuppressive myeloid cells. Despite various drugs aiming at the TME, no standout winner has emerged, prompting Dr. Keenan to discuss potential strategies for more effective interventions.
She highlights exploring metabolic byproducts with higher concentrations in the TME, using adenosine inhibitors as an example due to their inhibitory effects on the immune system. Myeloid cells, displaying diverse phenotypes, offer another target, either through inhibition or repolarization.
Dr. Keenan underscores the importance of personalized immunotherapy strategies based on the TME components. She envisions a future where immune profiling of tumors before therapy becomes routine, enabling the identification of critical elements in the TME that require targeting for a successful response.
Liver metastases, identified as a significant hurdle in immunotherapy response, are discussed in the context of their tolerogenic nature. Dr. Keenan acknowledges the challenges posed by liver metastases and the ongoing efforts to understand and overcome them, particularly focusing on T regulatory cells as potential drivers.
The presentation concludes with Dr. Keenan exploring adenosine inhibition as an anti-cancer therapy, noting modest response rates. She envisions the future development of adenosine-targeted therapies, emphasizing the importance of personalized approaches based on cancer types with high expression of relevant molecules. Additionally, she suggests combining adenosine inhibitors with other immunotherapies to enhance treatment efficacy.
By. Bartosz Chmielowski, MD PhD
In this presentation, Bartosz Chmielowski, MD PhD, discusses advancements in cancer therapy, focusing on approaches utilizing herpes virus-based treatments. The spotlight is on T VEC, the pioneering herpes virus therapy for cancer patients. The approval of this therapy was based on the durability of responses observed during clinical trials, demonstrating a heightened response rate compared to G-M-C-S-F injections alone.
Bartosz Chmielowski, MD PhD, emphasizes the specificity of T VEC, clarifying that it is tailored for patients with easily injectable diseases, limited to skin lesions or palpable lymph nodes. The therapy showcased a borderline improvement in overall survival, especially crucial at a time when large PD-1 blocking antibody results were not yet available.
The discussion then shifts to the combination therapy involving RP1, Fusolimod, and parapoxvirus, combined with nivolumab. Bartosz Chmielowski, MD PhD, details an overall objective response rate of 37.4%, offering hope for patients with primary and secondary resistance to anti-PD-1 therapy. This new herpes-based virus is anticipated to enhance infectivity in cancer cells and improve antigen presentation, presenting a potential option for patients progressing on PD-1 blocking antibodies.
The dialogue delves into intralesional therapy with cytokines, specifically IL-12 (tavokinogene telsaplasmid). Bartosz Chmielowski, MD PhD, notes the challenges faced with systemic IL-12 administration due to significant side effects, leading to the development of electroporation methods. While initial trials displayed promise, subsequent confirmatory trials, particularly in combination with pembrolizumab, yielded less favorable results. Despite setbacks, ongoing efforts explore alternative delivery methods for IL-12.
The conversation evolves to address the need for personalized treatment in PD-1 progressors and the scarcity of biopsies to validate activity and establish biomarkers. Bartosz Chmielowski, MD PhD, advocates for smaller, lab-focused trials, emphasizing the importance of linking clinical observations with laboratory analyses. The heterogeneity of resistance mechanisms prompts a call for tailored therapies based on individual patient profiles.
The presentation concludes with a discussion on innate immune agonists like Vigitalimod, CMP001, and Tilsitolimod (IMO2125). Bartosz Chmielowski, MD PhD, expresses interest in these therapies' potential to activate dendritic cells, enhancing antigen presentation and immune response. However, the need for confirmatory randomized trials remains paramount to validate and translate these responses into clinical outcomes.
In summary, Bartosz Chmielowski, MD PhD, offers an overview of the evolving landscape of herpes virus-based therapies, emphasizing the need for personalized treatments and ongoing research to address challenges in cancer therapy.
By. Anna M. Wu, MD, PhD
Anna M. Wu, MD, PhD, discussed the use of immunotherapy in patients who underwent melanoma resection and reviewed drug development strategies in this field. She traced the progression from treating advanced, unresectable cases to improved outcomes in stage three and node-negative diseases.
Wu highlighted the shift from post-surgery to pre-surgery immunotherapy, citing the S1801 clinical trial's significant improvement in event-free survival with pre-surgery treatment. She discussed ongoing trials and emerging data on effective combinations, including early outcomes of a cancer vaccine in melanoma.
Regarding the future of immunotherapy, Wu mentioned combining drugs like nivolumab and melatomab to potentially extend efficacy to resected stage three disease. She acknowledged the challenge of balancing effectiveness with potential side effects and expressed hope for advancements leading to less invasive surgeries.
Addressing the duration of immunotherapy treatment, Wu discussed ongoing debates about optimal periods and efforts to explore shorter treatment durations. She emphasized ongoing research into biomarkers of response, recognizing individual variations in the ideal treatment duration.
In conclusion, Anna M. Wu provided insights into the evolving landscape of immunotherapy in melanoma, showcasing advancements in treatment strategies and expressing optimism for future developments.
By. Arta Monjazeb, MD
Arta Monir Monjazeb, MD, explores cancer immunotherapy with a detailed discussion on the immune response, radiation's role, and the challenges of combining radiotherapy with immune checkpoint inhibitors (ICI). As a prominent figure in the field, Dr. Monjazeb brings forth insights that bridge clinical practice and research.
In an exploration of the immune response, Dr. Monjazeb emphasizes the role of antigen-presenting cells in transitioning from innate to adaptive immunity. He discusses the intricate relationship between radiation and the immune system, emphasizing the importance of immunogenic cell death and the subsequent activation of T cells.
Touching upon disparities among cancer types, Dr. Monjazeb articulates the varying effects of radiation and the need for tailored approaches. His discourse extends to the combination of radiation and immune checkpoint inhibitors, showcasing successes observed in non-small cell lung cancer. With a measured perspective, he questions whether these triumphs are inherent to the cancer type or a consequence of focused research.
The conversation takes a pragmatic turn as Dr. Monjazeb acknowledges the hurdles in combining radiotherapy with ICI, citing trial outcomes. He dissects the challenges, questioning the appropriateness of radiation doses, fractionation, and timing. Dr. Monjazeb highlights the critical need for a deeper understanding of the optimal conditions for combining these therapeutic modalities.
In response to the interviewer's probing on strategies for improvement, Dr. Monjazeb delineates a two-fold approach. First, he scrutinizes the methodology of testing radiation, emphasizing the necessity of refining the dose, fractionation, and timing. Second, he postulates that radiation alone may not suffice for cancers resistant to immune checkpoint inhibitors, advocating for a combination with immunostimulatory agents to enhance the immune response.
The interview culminates in a discussion of a canine trial involving radiation, the TLR9 agonist SD 101, and the IDO inhibitor epacadostat. Dr. Monjazeb elucidates the rationale behind the selection of these agents, drawing from previous studies at Stanford. The trial aims to address limitations observed in earlier efforts by blocking IDO, potentially amplifying the treatment's effectiveness.
In this conversation, Dr. Arta Monjazeb, MD, emerges as a thought leader navigating the complexities of cancer immunotherapy, offering valuable perspectives on the immune response, challenges faced, and innovative strategies to enhance therapeutic outcomes.
By. Greg Daniels, MD
In this discussion, Dr. Greg Daniels, a physician in the field of solid organ transplantation, provides information on the complexities faced by transplant patients, particularly those who have undergone kidney or heart transplants. With experience, Dr. Daniels emphasizes the role of immune suppressive drugs in maintaining the viability of transplanted organs, preventing rejection by the recipient's body.
Dr. Daniels elucidates the various immune suppressive agents used, highlighting the differences among them. Notably, he underscores the risk of cancer, particularly skin cancers such as cutaneous squamous cell carcinoma, as a concern for transplant patients. The physician discusses the importance of understanding the duration and depth of immune suppression and the specific agents used, as these factors contribute to the risk of developing malignancies.
The conversation touches upon the reality that successful organ transplants can be overshadowed by the emergence of cancer, impacting outcomes for patients. Dr. Daniels delves into the decision-making process when faced with complications like wound infections and disease progression, emphasizing the need for a multidisciplinary approach and consideration of treatment options, particularly avoiding cytotoxic chemotherapies and EGFR inhibitors unless absolutely necessary.
Addressing a specific case involving recurrent cutaneous squamous cell carcinoma in a renal transplant patient, Dr. Daniels discusses the challenges posed by wound infections and the limitations of certain immune suppressive agents. He explores the use of experimental immune therapies, cautioning about the associated risks and the necessity of collaboration with transplant centers to minimize the potential loss of the transplanted organ.
The discussion extends to the safety of immunotherapy in immunosuppressed patients, with Dr. Daniels presenting insights from a study involving RP1, an oncolytic herpesvirus. He emphasizes the importance of precautions, including biosafety measures, and notes the safety profile observed in the study compared to similar trials in non-transplant patients.
In the concluding segment, Dr. Daniels underscores the importance of prevention in managing skin cancers in solid organ transplant recipients. He advocates for a proactive approach, integrating dermatology into the care of transplant patients before the transplantation process begins. Dr. Daniels emphasizes the need for a comprehensive dermatology program focused on identifying and treating pre-existing skin issues, employing strategies such as sun protection, smoking cessation, and specific preventive measures to reduce the overall risk of skin cancers in this vulnerable population.
By. Katy Tsai, MD
Katy Tsai, MD, discusses the progress in cancer survivorship on a national scale, citing data from the American Cancer Society projecting a significant increase in the number of cancer survivors in the United States over the next decade. Katy Tsai, specializing in treating advanced melanoma skin cancer patients, reflects on advancements in melanoma survivorship with the introduction of immune checkpoint inhibitors.
In her dialogue, Katy Tsai delves into the historical context, emphasizing the shift from dire prognoses for metastatic melanoma patients to outcomes with contemporary treatments. She specifically mentions the success of combination immune checkpoint inhibitor blockade, such as the combination of ipilimumab plus nivolumab, showcasing substantial survival rates beyond the once-dreaded one-year mark.
During the interview, the conversation transitions to Katy Tsai's expertise in immune-related adverse events (IRAEs) associated with immune checkpoint inhibitors. She articulates challenges in predicting the frequency and onset of these events, especially with varying severity between anti CTLA4 and anti-PD-1/L1 agents. Katy Tsai discusses ongoing research aimed at refining management strategies, emphasizing the need for a better understanding of the underlying reasons behind IRAEs.
The interviewer prompts Katy Tsai to elaborate on the general management guidelines, specifically focusing on the Common Terminology Criteria for Adverse Events (CTCAE). Katy Tsai acknowledges the utility of standardized codification in discussing IRAEs' severity but highlights the dynamic nature of severity grading, particularly in refractory cases or instances of persistent toxicity. She underscores the importance of early intervention and adaptability in response to patients' evolving conditions.
The interview further explores the balance between managing IRAEs with glucocorticoids and ensuring optimal cancer treatment efficacy. Katy Tsai addresses the complexities of this issue, citing conflicting data on the impact of high-dose steroid use on overall survival. She emphasizes the need for nuanced approaches, considering the potential blunting of anti-tumor efficacy with glucocorticoid use.
In the final segment, the interviewer delves into the prognostication of chronic IRAEs, their recognition, and long-term implications for patients undergoing immunotherapy. Katy Tsai acknowledges the early stages of exploration in this area, citing a notable paper from Vanderbilt University as a step in standardizing definitions and increasing awareness of chronic IRAEs. She expresses optimism about collaborative efforts to gather data across different cancer types and contexts of immunotherapy use, contributing to a more comprehensive understanding of these prolonged adverse events.
By. Kim Margolin, MD
In the field of cancer immunotherapy, Kim Margolin, MD, provides insights into the interplay between the innate and adaptive immune systems. According to her, the innate immune system serves as a bridge, reacting swiftly against pathogens. This orchestration involves the secretion of cytokines, cytotoxic granules, and the engulfing of pathogens. Margolin emphasizes the concert between innate and adaptive immune responses, highlighting the significance of acute inflammation in anticancer reactions, in contrast to immunosuppression associated with chronic inflammation.
Margolin delves into the field of tertiary lymphoid structures within tumors, elucidating their composition, which mirrors that of the adaptive immune system. She emphasizes the dynamic nature of tumor stroma, dispelling the notion of static, structural elements. The stromal cells, including cancer-associated fibroblasts and various dendritic cell types, contribute functionally, playing crucial roles in immune reactions against pathogens and cancer.
Turning her attention to the microbiota, Margolin discusses its role in cancer immunotherapy. Focusing primarily on the gut microbiome, she elaborates on studies revealing certain bacteria associated with responses to immunotherapy. She discusses therapeutic interventions involving the transfer of fecal microbiome from immunotherapy-responsive animals to enhance outcomes in mice. Margolin suggests that understanding the nucleic acids of bacteria could pave the way for future therapeutic advancements.
Margolin then explores the landscape of cancer immunotherapy, investigating antigens and delivery approaches. Neoantigens, generated by mutations in cancer cells' DNA, stand out as targets. Sequencing these neoantigens allows for the creation of vaccines that stimulate adaptive immune responses. She highlights the diversity of vaccine approaches, ranging from killed cells to recombinant DNA-based substances, each undergoing rigorous study for efficacy against different cancer types.
The discussion concludes with a focus on the flip side of immunotherapy success—immune-related toxicities. Margolin acknowledges the breakthroughs in immune checkpoint blockade therapy but underscores the challenge of breaking tolerance, leading to potential autoimmune-like reactions. She discusses the use of immunosuppressive drugs to manage these adverse effects, noting that patients typically retain control over cancer, even after necessary interventions to counter immune-related toxicities. While the field is not without its challenges, Margolin expresses optimism about the ongoing progress in balancing the therapeutic benefits and potential side effects of cancer immunotherapy.
By: Allison Betof Warner, MD, PhD, Stanford
Immuno-Oncology Determining Optimal Treatment Duration
The question of how long to treat patients is one of the more challenging ones in our field. It's always wonderful when our patients are responding. Classically in oncology, we kept patients on treatment indefinitely in the days of chemotherapy and even targeted therapy. Um, but we really feel that the immune system can learn to take care of a cancer itself from immunotherapy.
And all of the data have suggested that over the years. the question is, how do we pick which patient is the right patient to discontinue? Um, and at what time point? And so the earliest studies, you know, planned immunotherapy indefinitely, then many set a cutoff of two years as a stopping date. And that's really when, you know, where most of the data lie at a two year stopping date.
And what we've seen is that patients really do quite well, particularly the patients who have a complete response or a deep partial response. They really do quite well if they discontinue treatment after two years. The question lies in can we stop earlier, right? Trying to avoid toxicity. Certainly trying to avoid the cost of treatment both for patients and for the healthcare system.
Um, you know, we are running into the issue of not enough treatment beds, not enough treatment chairs as a healthcare system. Um, certainly as well as the high dollar cost of these medicines. So if we could safely discontinue patients earlier that gets them back to their life. That, you know, reduces the risk that they will develop a new side effect late, although that is somewhat uncommon, but certainly saves us and the healthcare system a lot of money, um, time, hassle, time away from work, et cetera.
Um, there are several studies trying to examine this question, but really right now we're very reliant on retrospective data looking at what's been done, you know, across systems. And so we've looked back at certainly those clinical trials that planned stopping at two years and we know, as I said earlier, that patients who have a complete response and even patients who have a deep partial response have excellent outcomes.
You know, two, three, five years later, um, But what is harder is in a real world population, in a population outside of a clinical trial who didn't have a perfectly prescribed course. So my group published on this a few years ago looking at 102 patients who had a complete response who were not treated for a planned two years, but that actually the vast majority of those patients discontinued treatment.
right after they had a complete response. Um, this was a single center series, and so it's certainly not comprehensive by any stretch of the imagination. But those patients did quite well long term as well, maybe not quite overall as well. But in a real world population, 75 ish percent of them still had not required additional treatment years down the road.
Overall, we are looking at prospective clinical trials to try to answer this question. There's an ongoing trial called Pet Stop, uh, led by Jeff Gibney at Georgetown University. Um, that is doing a plan stopping of treatment at a one year. If patients have a negative. PET scan or a PET scan that's positive, but the biopsy shows no viable disease and then following outcomes and recurrence for those patients.
Um, and some randomized trials that are occurring internationally that I think will help us define this better. But at this point, I'm counseling my patients, you know. That all of the data suggests that if you're tolerating treatment well, we stay on somewhere between one and two years. And then we plan to stop at that point.
Can you provide insights into the challenges and decision making process in defining the duration of therapy, especially when faced with durable responses, as seen in the Keynote 001 study? Yeah, so the keynote 001 study looked at single agent pembrolizumab for the treatment of advanced unresectable melanoma.
And the vast majority of those patients were treated for about two years. The median duration on treatment was 23 months. And what they saw was patients who had a complete response in that study, years later, 90 percent of them still had not required any additional treatment after stopping at that median of 23 months.
So that provided a lot of reassurance that at least some patients and our best responders can safely discontinue treatment. Your presentation highlighted the results of real world studies on the duration of PD 1 therapy for melanoma, showing a median time on treatment of 9. 4 months with a 3 year treatment free survival of 72.
1%. How do these findings align with or differ from expectations based on clinical trial data? Yeah, so... This was a single center study that I conducted when I was at Memorial Sloan Kettering, um, of 102 patients who had a complete response. And at that time, there was a big push to discontinue treatment as soon as possible.
Right, we'd swung from keep patients on treatment forever, or... You know, long periods of time to get them off treatment as soon as they're responding very well to try to avoid side effects and long term type and long term toxicity. And so the median time on treatment in those patients was actually about nine months.
So much less than clinical trials that pre specified patients would stay on for two years. Um, and the median time on treatment after a complete response was actually zero months. So many patients stopping right around the time of their complete response. Now some of those patients stopped for toxicity, so that is unavoidable, but many opted to stop treatment because of that complete response at that time.
This was not a prospective study, this was just a retrospective look at those patients. Um, But overall, you know, at three years, 72 percent of those patients still had not required additional treatment. That is not the 90%, for example, or 88 percent that we saw from Keynote 001, but still a really excellent percentage of patients who were spared quite a bit of treatment.
Um, One of the keys to understand, though, is that we don't know if the difference is just a difference in the patients or a difference in the duration that they were treated, right? A real world population typically performs differently than a clinical trial, even if they got exactly the same treatment.
So these retrospective analyses, they're helpful and they're the best data that we have right now. But we can't just extrapolate from that and say, well, they got shorter duration of treatment and, you know, a higher percentage of them recurred. So longer is better. I think that's a really important point.
This, these are hypothesis generating. Then we need to do the prospective clinical trial that answers this question. Could you provide more details on the PET STOP study, the key objectives, and any preliminary findings that may shed light on the optimal treatment duration in advanced melanoma? The PET STOP study is led by my colleague and friend, Jeff Gibney, at Georgetown University, but it's a cooperative group trial taking place across the United States.
This trial enrolls patients, um, who have had a... complete response at one year. So you get a PET scan. If the PET scan is absolutely negative, patients have a planned stop of treatment. If the PET scan is positive, you then do a biopsy. If the biopsy does not show any viable melanoma, those patients stop treatment.
If there is viable melanoma, the patients stay on treatment for another year. It's a non randomized trial. It's a single arm. Um, and the, uh, end point here is progression free survival. This is, you know, Attempting to look at can we stop at one year, at least for these best responders, these complete responders, rather than keeping patients on for a total of two years.
I would say it's still too early to talk about results yet. actively accruing and we are looking for more sites across the U. S. Really trying to get these patients so we can categorize and really know how to advise our colleagues and our patients about best discontinuation. But at this point, still a bit too early to talk about data.
Your presentation touched on the other study and the prospective trial checkmate 1 53 in non small cell lung cancer. Can you discuss the challenges and insights gained from these different cancer types and the influence on immunotherapy duration in oncology? You know, the other study is a meta analysis.
It's a retrospective look at all of the studies that have been done across different cancers. So, while these can be helpful, they're still limited by the fact that this was not a planned analysis. Um, and the biggest thing that we saw from the other study was there wasn't a strong, strong signal that staying on treatment was better for any cancer, um, you know, beyond at least the two year mark, which was the cutoff that was used in that study.
Other than that, I think it's really hard to draw conclusions. The confidence intervals are very large from that study and, you know, without a prospect It's very difficult to really make clear treatment recommendations based on that. Checkmate 153 was a prospective randomized trial in non small cell lung cancer that randomized patients to getting treated for one year versus continuous treatment.
Um, In that study, patients who were treated for longer actually did better in terms of progression free survival and event free survival. Um, can we take that as gospel across all cancers, even across non small cell lung cancer? Probably not, but it is the best prospective data we have that does certainly raise questions about whether one year is sufficient, at least in an all comers population.
Now, had we broken that down by just... complete responders and stopped at one year. Some of those subgroup analyses were done, but that was a relatively small trial, um, to do that. I think it also, you know, many of us have used a two year cutoff rather than a one year cutoff, um, and advise our patients who have excellent responses to do two years of treatment.
And so, you know, certainly that trial does not answer the two year versus one year. question. It was indefinite versus one year. Um, but I do think it is an example of the type of trial that we need to truly answer this question. But it's important to know that non small cell lung cancer may be different from melanoma, may be different from renal cell cancer, and we may truly need to do these trials across all of our tumor types to really understand how to best counsel our patients.
Elizabeth Brem , MD discusses the design and outcomes of the study referred to as 1826. The study aimed to enhance outcomes and address toxicities in Hodgkin lymphoma treatment. Nivolumab's potential benefits in comparison to brentuximab within the AVD backbone were explored. Additionally, Brem highlights the collaborative nature of the study, involving adult and pediatric cooperative groups, Canadian cooperative groups, and the children's oncology group. This collaboration played a pivotal role in the trial's success, enabling rapid accrual and earlier achievement of primary endpoints.
Elizabeth Brem emphasizes that the study achieved its primary objective by improving progression-free survival in patients with Hodgkin lymphoma. While overall survival benefits weren't immediately evident, Brem underscores the impressive achievement of curbing toxicity. The study demonstrates that the nivolumab ABD regimen offers greater tolerability compared to brentuximab AVD, addressing concerns about neuropathy and neutropenia.
Addressing Hodgkin's disease's unique nature and the positive outcomes seen, Brem stresses the importance of mitigating toxicity, especially given the younger age of the patients. She emphasizes that sparing patients long-term toxicity, particularly peripheral neuropathy, is significant. Brem also highlights the lack of significant autoimmune toxicity in the nivolumab AVD arm, possibly due to the combination with chemotherapy and the limited treatment duration.
In terms of durability, Brem acknowledges the conventional focus on improved PFS and emphasizes how the study's findings in the context of malignant hematology might differ from solid tumor cases. She considers the costs associated with both regimens but suggests that the toxicity profile of nivolumab AVD is a compelling reason to adopt it. The question remains about the long-term sustainability of the benefits, and Brem anticipates the need for extended patient follow-up to validate the sustained PFS improvement.
Shirin Attarian, MD addresses the escalating incidence of head and neck cancer and highlights that most cases, particularly oropharyngeal cancers, are driven by HPV virus infection.
She discusses HPV vaccination recommendations, suggesting that individuals between 11 and 26 years old should be vaccinated, potentially starting from age 9. Vaccination for those aged 27-45 is possible after physician consultation but might be less effective due to prior exposure. Beyond 45, there are no current vaccination recommendations. Attarian explains that despite younger generations getting vaccinated, the incidence of head and neck cancer is anticipated to rise in older individuals who aren't vaccinated.
Regarding the Jupiter Two trial's significance in immunotherapy, Shirin Attarian, MD discusses the reported improvements in progression-free survival and overall survival using Tauropalbap combined with Gyncytamine and Cisplatin as a first-line treatment for recurrent metastatic head and nasal pharyngeal disease. Attarian emphasizes the importance of these findings as they introduce a role for PD1 inhibition in this disease context and potentially pave the way for approvals based on future data from other trials.
Discussing the Continuum trial focused on non-metastatic high-risk locally advanced nasopharyngeal carcinoma, Attarian explains how adding Sintilamab, a PD-1 inhibitor, to the standard treatment regimen leads to improved event-free survival. She notes that overall survival data is still maturing due to the nature of the disease, requiring longer follow-up to confirm differences.
In the FRAIL Immune Trial, which explores Dervo Lomia in cisplatin-ineligible patients with recurrent metastatic head and neck cancer, Attarian highlights the importance of this study for patients with limited treatment options. The trial's addition of Dervalumab to weekly Carboplatin and Paclitaxel yielded a promising overall survival of 18 months, offering a potential option for this patient group.
Regarding the DEPEND trial's approach involving Dervalumab-based neoadjuvant chemotherapy followed by response-adaptive CRT for locally advanced HPV-negative head and neck cancer, Attarian emphasizes the trial's intriguing strategy. It assessed a reduction in radiation dose for patients responding well to induction chemoimmunotherapy. Those with a significant tumor size reduction received lower-dose radiation, yielding improved outcomes, survival, and tolerability. Attarian underscores the importance of larger studies to validate the role of this response-adaptive strategy.
Nataliya Mar, MD Clinical Associate Professor in the Division of Hematology/Oncology at the University of California Irvine, provides GU ASCO Updates .
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