By Amanda J. Redig, SVP and Head of Clinical Development at HotSpot Therapeutics, as part of the From The Trenches feature of LifeSciVC
The American Cancer Society for Oncology (ASCO) annual meeting is among the highlights of the clinical oncology calendar. The meeting brings together tens of thousands of physicians, scientists, patients, advocates, innovators, and those involved in oncology drug development from around the world in order to explore the latest advances in cancer treatment, clinical trials, and translational and clinical research.
From my perspective as a medical oncologist with experience across academic practice, industry drug development, and life sciences investing, the energy at this meeting is uniquely palpable. Even though the scale of the meeting can be daunting, it’s one of the few times when (almost) everyone on the list of one’s colleagues and contacts might be under one very large roof. And sometimes when data is shared publicly for the first time—whether from an early proof-of-concept study like the 100% response rate in advanced myeloma in the first-in-human Ph1 of the LCAR-B38M BCMA cell therapy that became Carvykti® (ciltacabtagene-autoluecel) or from a pivotal Ph3 trial like the Destiny-Breast04 study showing a 50% reduction in death or progression with the HER2-antibody drug conjugate Enhertu® (fam-trastuzumab deruxtecan-nxki) in women with advanced HER2-low breast cancer—you know that you are witnessing history.
The landscape of clinical oncology is almost unrecognizable from the standard of care even 10 years ago, and with this year’s meeting theme of “Partnering with Patients: The Cornerstone of Cancer Care and Research” selected by 2022-2023 ASCO President Eric P. Winer, MD, FASCO, here are my takeaways from the first week of June in Chicago.
1. Novel Mechanisms Not As Front and Center
Although previous ASCO meetings in recent memory have been notable for spotlighting the emergence of a clearly game-changing mechanism-of-action (PD-1 inhibitors, cell therapies, and bispecific antibodies come to mind), the 2023 Annual Meeting repeatedly highlighted the evolving and expanding use of validated targets and/or therapeutic mechanism-of-action.
In keeping with the theme of this year’s meeting, this is a great step forward for patients. The majority of new cancer drugs will be approved in late-line settings in patients with advanced disease. It is always meaningful to provide new options for patients who no longer have any, but what is perhaps even more impactful is the opportunity to take a winning drug in late-line patients and show that it can drive truly long-term durable response, maybe even cures, when used in patients with early-stage disease. The KEYNOTE-671 (pembrolizumab) and ADAURA (osimertinib) studies both illustrate this to striking effect and remind us that the path to progress has only begun with the first approval of a novel agent: both pembrolizumab and osimertinib were initially approved as monotherapy for advanced NSCLC in 2015.
2. Immunotherapy for the Win
The transformative power of immunotherapy continues to dominate the landscape of standard-of-care oncology treatment as well as a significant number of trials across all stages of development. The previously mentioned KEYNOTE-671 study was just one of many presented trials across multiple tumor types and practice settings in which moving immunotherapy into earlier lines of therapy continues to drive ever-increasing benefit for a larger group of patients. In addition, we are also starting to see studies in which novel combinations of immunotherapies or immunotherapy/targeted therapy combinations suggest that in the right tumor context, two highly active immunotherapies or a targeted combination can perhaps be even more impressive than the sum of their parts. Finally, as the S1826 study from the SWOG study group demonstrated in the plenary session, in a head-to-head comparison of a highly effective immunotherapy regimen vs a highly effective targeted therapy regimen in Hodgkin lymphoma, the immunotherapy regimen emerged with a striking progression-free survival benefit at 1 year.
3. Trial Design in Early Phase Development Matters
One of the most discussed late-stage studies presented at this year’s meeting was the NATALEE trial establishing the survival benefit of endocrine therapy plus the CDK4/6 inhibitor ribociclib as adjuvant therapy in women with hormone receptor+/HER2- Stage II-III breast cancer. In addition to the data, the execution of this study is an achievement in itself: it required the randomization of over 5100 patients in a global trial. As therapeutic options become both more effective and more numerous, the cost, complexity, and time required to advance the standard-of-care continues to grow. Effectively leveraging emerging therapies and doing so in an efficient way—a process that begins with the strategic decisions made in early development—will continue to require increasing levels of collaboration across the clinical practice and industry continuum to shape the development plan of promising new agents. The utilization of flexible Ph1/2 study protocols, the use of predictive/prognostic biomarkers whenever possible to identify patient subgroups most likely to benefit from an intervention, and the use of adaptive trial designs are some of the strategies that will continue to be relevant as we move into a future where the existing standard of care is increasingly a higher and higher bar.
4. Less is More: Limiting Therapy Without Sacrificing Efficacy
The history of cancer therapies is one of intensive and aggressive interventions that often carried a morbidity and mortality risk that wasn’t entirely dissimilar to the underlying diagnosis. In an era of ever more effective therapies, it is encouraging to see studies start to emerge that help answer the question of how much is enough—and when can we do less and still have the same outcome? From limiting the use of lymph node dissection in some patients with melanoma to utilizing biomarker strategies to tailor the use of neoadjuvant immunotherapy or chemotherapy in women with early-stage breast cancer to minimizing the use of radiation in patients with lymphoma, the future of oncology treatment strategies will continue to focus on maximizing benefit while minimizing the clinical and financial toxicities of oncology therapy.
While the themes and trends in emerging data may vary from ASCO to ASCO, the one theme that remains constant is the critical role of the patient as a partner in any clinical development journey. In his presidential address, outgoing ASCO president Dr. Eric Winer shared an inspiring and deeply personal set of reflections on the patient experience, drawing from not only his career as an oncologist, but also his experience as a patient living with hemophilia. His remarks are worth reading in their entirety. And as Dr. Winer so eloquently stated in his remarks, no matter what data may be ready for topline presentation at ASCO 2024, we know this to be true: “Science really matters. We owe it to our patients to step firmly on the scientific accelerator.”
