null New study of therapy options in metastatic melanoma

RI-MUHC researchers lead “real-world” analysis of treatment patterns with checkpoint inhibitors

September 18, 2020

Source: RI-MUHC. Melanoma is the least common but most serious type of skin cancer. In Canada, melanoma incidence is increasing; in 2020, 8,000 Canadians will be diagnosed with melanoma and 1,300 will die from this disease. When melanoma spreads to other parts of the body, such as the lung, liver or brain, survival is drastically reduced. For patients at this stage, known as metastatic melanoma, novel drugs called immune checkpoint inhibitors have transformed the landscape of treatment, increasing response and survival rates. However, some patients may discontinue checkpoint therapy when it becomes ineffective or due to drug toxicity.

In a new study published in the journal Scientific Reports, a group of researchers described treatment patterns of checkpoint inhibitors in patients with metastatic melanoma in a “real-world” setting. Led by Sasha Bernatsky, MD, PhD, James McGill Professor of Medicine at McGill University and senior scientist at the Research Institute of the McGill University Health Centre (RI-MUHC), the team selected eight hundred U.S. patients with metastatic melanoma who initiated checkpoint therapy between 2015 and 2017. The main objective was to estimate how many patients discontinued the initial checkpoint therapy, while comparing three treatment regimens: pembrolizumab, nivolumab, and combination therapy of nivolumab and ipilimumab.

Postdoctoral fellow and lead author Marina Machado, PhD, and Dr. Sasha Bernatsky, senior scientist at the Research Institute of the MUHC
Postdoctoral fellow and lead author Marina Machado, PhD, and Dr. Sasha Bernatsky, senior scientist at the Research Institute of the MUHC

“Checkpoint inhibitors have recently become commonly used first-line therapies in metastatic melanoma, but the optimal duration of therapy remains unknown,” says Dr. Bernatsky, who is a member of the Infectious Diseases and Immunity in Global Health Program and conducts research at the Centre for Outcomes Research and Evaluation at the RI-MUHC. Dr. Bernatsky also leads the Canadian Network for Advanced Interdisciplinary Method (CAN-AIM) team, funded through the Drug Safety and Effectiveness Network of the Canadian Institutes of Health Research.

Findings from the study show that during the first year of follow-up, 50 to 60 percent of patients discontinued checkpoint therapy. Although the difference in therapy discontinuation was very small or not detectable between different checkpoint therapies, there were trends for lower discontinuation with pembrolizumab. Patients using nivolumab/ipilimumab were more likely to stop therapy and to receive systemic corticosteroid, suggesting more short-term toxicities related to immune system overactivity. Patients using nivolumab tended to initiate another cancer therapy earlier, which may have been due to signs that the melanoma was advancing. In this investigation, pembrolizumab was more commonly used (44%) than nivolumab (25%). These findings may suggest a slight preference for pembrolizumab versus nivolumab, possibly due to different dosing schedules (one injection every three weeks for pembrolizumab versus every two weeks for nivolumab).

“Our goal is to better understand immune checkpoint inhibitors, and ultimately their ability to increase melanoma survival rates,” says Marina Machado, PhD, a postdoctoral fellow at the RI-MUHC and lead author on the study. “There is still a need for further investigations to confirm these results and to evaluate other aspects of treatment.”

About the study

Machado, M.A.d., de Moura, C.S., Chan, K. et al. Real-world analyses of therapy discontinuation of checkpoint inhibitors in metastatic melanoma patients. Sci Rep 10, 14607 (2020).