Jason J. Luke, MD, on Melanoma Adjuvant Therapy: Final Analysis of KEYNOTE-716
2023 ASCO Annual Meeting
Jason J. Luke, MD, of the University of Pittsburgh Medical Center Hillman Cancer Center, discusses adjuvant pembrolizumab, which, in previous results, improved distant metastasis– and recurrence-free survival in patients with resected stage IIB or IIC melanoma vs placebo. After a median follow-up of 39.4 months, adjuvant pembrolizumab continued to show a benefit over placebo, with no new safety signals (Abstract LBA9505).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Adjuvant therapy for melanoma has been shifting rapidly and really to the betterment to the patients that were treated in our clinics. KEYNOTE-716 was the placebo controlled phase three clinical trial that demonstrated that pembrolizumab improves recurrence-free and distant metastasis free survival for patients with 2B and 2C melanoma. And of course, the context for this clinical trial was that we've been using adjuvant therapy for stage three melanoma for several years, and yet it wasn't available for patients with stage two. But that being said, the melanoma specific survival of patients with stage 2B and 2C melanoma has been known to actually be worse than that for patients with stage 3A and 3B melanoma, and yet we couldn't treat them. So we launched KEYNOTE-716 really to try to level set the field to give access to patients for a treatment that we know works for patients with similar risk.
So to update the study now, we're presenting Landmark 36 month data with a median of 39 months of follow-up, showing that the recurrence-free survival, but more importantly, distant metastases free survival continues to be maintained and in fact increases in magnitude of benefit with further follow up on the clinical trial. And these are very, very important data for multiple reasons. One, is that they really emphasize this point that patients with stage 2B and 2C melanoma are at high risk of recurrence. But more than that, that adjuvant pembrolizumab is now the standard of care that should be offered to these patients.
Now, of course, there is nuance to the decision about whether or not to choose adjuvant therapy in the postoperative setting. We have to take into account the risks and the benefits. It's clear now that the benefits include more than a 4% reduction in the likelihood of distant metastasis. There are side effects that are associated with immunotherapy, immune related adverse events, which no doubt can take place and be life altering in up to 5% of patients. So that's really where the crux is. With an individual patient, is it worth it to consider an adjuvant therapy that can significantly reduce your risk, albeit potentially also enhance side effect profile?
So I think these data are very important to level set the field. Again, this is a very rapidly moving field, and these data show the landmarks and the benchmarks of what we should expect moving forward. There are multiple adjuvant clinical trials, phase three randomized studies that are now looking to further enhance the standard of care. And these include checkpoint combinations with molecules targeting lag three and tigit, and more recently, the individualized neo antigen therapies that have looked very, very promising. And so we know now that patients with stage two should be included in those clinical trials, and in fact, they are. And I think for the future moving forward, the perioperative setting for adjuvant therapy really will include all patients with stage 2B all the way through stage four resected melanoma.
Narjust Florez, MD, of Dana-Farber Cancer Institute, and Ticiana Leal, MD, of Winship Cancer Institute of Emory University, discuss the use of tumor treating fields therapy, in which electric fields disrupt processes critical for cancer cell viability. Already approved by the FDA to treat glioblastoma and mesothelioma, the treatment has extended overall survival in this phase III study of patients with metastatic non–small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy, without exacerbating systemic toxicities (Abstract LBA9005).
Muhit Özcan, MD, of Turkey’s Ankara University School of Medicine, discusses waveLINE-007, a two-part study now recruiting in more than 20 locations, to determine the safety and recommended phase II dose of the antibody-drug conjugate zilovertamab vedotin in combination with R-CHP (rituximab, cyclophosphamide, doxorubicin, prednisone) in previously untreated patients with diffuse large B-cell lymphoma (DLBCL). Efficacy of this regimen will be investigated in the second half of the study (Abstract TPS7589).
Bobbie J. Rimel, MD, of Cedars-Sinai Medical Center, and Mansoor R. Mirza, MD, of Denmark’s Rigshospitalet and Copenhagen University Hospital, discuss new findings on dostarlimab-gxly plus carboplatin/paclitaxel, which improved progression-free survival while maintaining health-related quality of life, further supporting its use as a standard of care in primary advanced or recurrent endometrial cancer (Abstract 5504).
Nirav N. Shah, MD, of the Medical College of Wisconsin, discusses the efficacy and safety of pirtobrutinib, a highly selective, noncovalent BTK inhibitor, studied for more than 3 years in the BRUIN trial. The results showed that the use of pirtobrutinib continues to have durable efficacy and a favorable safety profile in heavily pretreated patients with relapsed or refractory mantle cell lymphoma and prior BTK inhibitor therapy. Responses were observed in patients with high-risk disease features, including blastoid/pleomorphic variants, elevated Ki67 index, and TP53 mutations (Abstract 7514).
Cathy Eng, MD, of Vanderbilt-Ingram Cancer Center, and Thejus Jayakrishnan, MD, of the Cleveland Clinic Taussig Cancer Institute, discuss significant differences in the citrate cycle, a core pathway of cellular metabolism associated with colorectal cancer. Metabolomic differences impacted by environmental exposures (arginine biosynthesis and dietary red meat) were also noted, suggesting possible links with younger age of onset in this disease (Abstract 3510).