Treatment with immunotherapy has become ingrained in the standard of care for treating patients with melanoma, but investigators continue to research new combinations and treatment strategies that can improve patients outcomes. One approach that has generated a great deal of interest and is a significant focus of ongoing trials involves adjuvant and neoadjuvant therapy, according to Jeffrey S. Weber, MD, PhD.
Jeffrey S. Weber, MD, PhD
Treatment with immunotherapy has become ingrained in the standard of care for treating patients with melanoma, but investigators continue to research new combinations and treatment strategies that can improve patients outcomes. One approach that has generated a great deal of interest and is a significant focus of ongoing trials involves adjuvant and neoadjuvant therapy, according toJeffrey S. Weber, MD, PhD.
Weber, who is the deputy director of the Laura and Isaac Perlmutter Cancer Center at NYU Langone Health in New York, New York, will lead presentations and discussions on these advances at the16th AnnualInternational Symposium on Melanoma and Other Cutaneous Malignancies®, hosted by Physicians’ Education Resource®, LLC. Weber is cochair of the educational symposium, which focuses on emerging treatments in skin cancers and updates in clinical practice standards. The event, also cochaired byOmid Hamid, MD, director of the melanoma program at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute in Los Angeles, California, will take place Saturday, February 8, 2020, in New York City’s Times Square.
“You’re going to hear about the latest adjuvant and neoadjuvant data, and you’re going to hear about the latest updates in the use of either single-agent or combination immune therapy, as well as combination targeted therapy. Those are important standard-of-care items that would be of most importance to a practicing physician,” Weber toldTargeted Therapies in Oncology. During an interview, he described what oncologists can expect to hear at the symposium.
For example, Weber will moderate a session on the use of adjuvant therapy in melanoma, which will include aMedical Crossfire® on the role of both adjuvant and neoadjuvant therapy in melanoma. This debate-style discussion will be conducted jointly with Rodabe N. Amaria, MD, an assistant professor in the Department of Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center in Houston.
Omid Hamid, MD
Weber explained in the interview that physicians are interested in reusing currently available therapies before or after surgery to improve patient outcomes. One ongoing trial that he highlighted is the phase II SWOG S1801 trial, a randomized study of neoadjuvant pembrolizumab (Keytruda) versus adjuvant pembrolizumab in patients with high-risk, stage III to IV resectable melanoma (NCT03698019). Data from the trial are still years away, however.
Adjuvant treatment with PD-1 immune checkpoint inhibitors already can be used in the United States. The FDA approved pembrolizumab on February 15, 2019, for the adjuvant treatment of patients with melanoma and lymph node involvement following complete resection based on data from the EORTC1325/KEY- NOTE-054 trial. Results showed that treatment with the PD-1 inhibitor was favorable in terms of recurrence-free survival compared with placebo (HR, 0.57; 95% CI, 0.46-0.70;P<.001).1
Additionally, adjuvant nivolumab (Opdivo) was approved for patients with lymph node involvement or metastatic disease based on the phase III CheckMate 238 trial,2which Weber led. The findings demonstrated a 35% reduction in the risk of recurrence or death with the use of nivolumab compared with ipilimumab (Yervoy) in patients with stage IIIb/c or IV melanoma following surgical resection (HR, 0.65; 95% CI, 0.53- 0.80;P<.0001).3
Weber is proudest of accomplishing that advancement, he said: “There was resistance to wanting to do an adjuvant trial with a drug like nivolumab or like pembrolizumab. I didn’t buy that argument and stuck with it and did a pilot trial, which took a huge amount of effort.... The randomized trial was positive, and now thousands of patients in the United States every year are [receiving treatment] with adjuvant nivolumab or pembrolizumab, and the results are that it’s definitely reducing the risk of relapse. That’s what I feel good about.”
Another current focus of changing practice for managing melanoma is the use of immunotherapy, and research is moving toward the use of combination immunotherapy approaches.
During a Saturday morning presentation at the symposium, Weber will highlight the state-of-the-art immunotherapy treatments in melanoma management. He explained that investigators are searching for the optimal com- bination of therapies beyond the standard nivolumab/ipilimumab combination and single-agent checkpoint inhibitors. “The field is going [toward] optimal combinations of using new drugs to combine with PD-1 blockade that wouldn’t significantly improve or worsen the toxicity, so you would no longer have to use ipilimumab/nivolumab, which, frankly, is a pretty toxic combination. But right now, that’s the regimen to beat, at least in the United States,” Weber said.
Although there have been a few recent failures with combination trials, such as one of pembrolizumab with an indoleamine 2,3-dioxygenase 1 inhibitor, Weber remains hopeful that a combination will be found to improve outcomes for patients. For instance, he is the lead investigator of a new phase II clinical trial of the nivolumab/ipilimumab combination in addition to the IL-6 receptor inhibitor tocilizumab (Actemra) in patients with unresectable stage III or IV melanoma (NCT03999749), which is assessing the combination’s potential to reduce toxicity and/or increase efficacy.
“There’s already ample evidence in the literature that patients who have steroid-refractory colitis and other immune-related adverse events do respond to tocilizumab,” Weber explained. “Tocilizumab is an IL-6 receptorblocking antibody that’s approved for arthritis of different types, and it is used to block the cytokine release syndrome in patients getting CAR [chimeric antigen receptor] T cells, so there’s ample evidence that it can reduce immune toxicity in certain scenarios. This will be the first time we use it preventively to try to block the possibility of the adverse effects occurring.”
The symposium will also address the standards of care in nonmelanoma skin cancers and other cutaneous malignancies. Presentations will cover current best practices for management of ocular melanoma, cutaneous T-cell lymphoma, basal cell carcinoma, cutaneous squamous cell carcinoma, and Merkel cell carcinoma.
Leaders in the field will provide their expert perspectives on additional topics that may affect future management of melanoma, including the use of liquid biopsies, predictive biomarkers, and the microbiome. Amod A. Sarnaik, MD, associate professor of oncology and surgery at the University of South Florida and a surgical oncologist at Moffitt Cancer Center, both in Tampa, will discuss the potential use of adoptive T-cell therapy for treating melanoma.
Overall, the symposium will provide oncologists and other members of the cancer care team with expert insights into management strategies for patients with melanoma and other cutaneous malignancies, suggestions for handling immune-related toxicities, and a glimpse of what’s to come as emerging data change practice in the field.