Allison Betof Warner, MD, PhD
In a single-center study reported in the Journal of Clinical Oncology, Allison Betof Warner, MD, PhD, and colleagues found that approximately three-quarters of patients with advanced melanoma achieving a complete response on programmed cell death protein 1 (PD-1) inhibitor therapy were alive without further treatment at 3 years. Among all patients with disease progression retreated with immune checkpoint inhibitors, response was observed in a minority.
The study involved analysis of data from all 396 patients—the majority treated outside of a clinical trial—who received single-agent anti–PD-1 therapy for nonuveal unresectable stage III/IV melanoma at Memorial Sloan Kettering Cancer Center between 2009 and 2018. Included patients had discontinued treatment and had at least 3 months of follow-up after discontinuation. Overall survival for patients with a complete response was calculated from the time of complete response. Time to treatment failure for patients with a complete response was defined as time from complete response to next melanoma treatment or death.
Treatment and Retreatment Outcomes
In the entire cohort, the median time to treatment failure was 7.9 months, and 5-year treatment failure–free survival was 21.5%. The median overall survival was 39 months, and 5-year overall survival was 40.8%.
A complete response was observed in 102 (25.8%) of the 396 patients; in multivariate analysis, complete response was associated with M1b disease and cutaneous vs mucosal or acral primary sites. An additional 23.5% of patients had significant antitumor response that was less than complete response, and 11.6% had stable disease as their best response.
“In our cohort, most patients discontinued treatment at the time of complete response. Most complete responses were durable, but the probability of treatment failure was 27% at 3 years. Responses to retreatment were infrequent. The optimal duration of treatment after complete response is not yet established.”— Allison Betof Warner, MD, PhD, and colleagues
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The median number of months of treatment after complete response was 0 (range = stopped before complete response to 26 months after complete response). At a median follow-up of 21.1 months from time of complete response in patients who did not relapse, the probability of being alive and not requiring additional melanoma therapy at 3 years was 72.1%.
The estimated 3-year overall survival from time of complete response was 82.7%. Among patients who achieved and remained in complete response for 1 year after it was identified, the conditional probability of remaining in complete response for 2 more years was 83.3%. No significant association was observed between treatment duration and relapse risk.
A total of 78 patients who discontinued PD-1 inhibitor therapy for any reason and later experienced disease progression were retreated with immune checkpoint inhibitor therapy, including 10 who had initially achieved a complete response. A response was observed in 5 of 34 patients who received subsequent treatment with single-agent anti–PD-1 therapy and 11 of 44 who received anti–PD-1 plus ipilimumab therapy. Response was observed in 2 of 10 patients with an initial complete response.
The investigators concluded, “In our cohort, most patients discontinued treatment at the time of complete response. Most complete responses were durable, but the probability of treatment failure was 27% at 3 years. Responses to retreatment were infrequent. The optimal duration of treatment after complete response is not yet established.”
Dr. Betof Warner, of Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by a Young Investigator Award from the Conquer Cancer Foundation of ASCO, National Cancer Institute, and Parker Institute for Cancer Immunotherapy. For full disclosures of the study authors, visit ascopubs.org.
