1. Hackethal, Veronica

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Some patients with metastatic melanoma treated with PD-1 inhibitors may be able to successfully discontinue therapy after 1 year without sacrificing outcomes, according to results presented at the ASCO 2020 Annual Meeting (Abstract 10048). The study is the largest of its kind to date among real-world patients who electively discontinued PD-1 inhibitors after 1 year of treatment. The majority remained free of disease progression after almost 1 year of being off therapy.

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"Once patients show response to immunotherapy, these responses appear to be durable," said senior author Umang Swami, MD, Assistant Professor at the Huntsman Cancer Institute at the University of Utah, Salt Lake City. "Based on this evidence, we are having a discussion with our patients. These immunotherapies are very costly. If the maximum benefit is reached at 1 year, discontinuing therapy at that time could spare patients not only from financial toxicity but also treatment-related side effects. There might also be a potential financial benefit for health care system in general."


Clinical trials have established the effectiveness of PD-1 inhibitors in the treatment of metastatic melanoma. The problem is that trials were designed with a 2-year treatment course in the case of pembrolizumab, and indefinitely for nivolumab. That has left a lingering question: do patients with metastatic melanoma who respond to PD-1 inhibitors really need to stay on them so long?


Study Details

To find out, Swami and colleagues reviewed clinical outcomes among 52 patients treated with metastatic melanoma at the Huntsman Cancer Institute in Salt Lake City between January 2015 through December 2018. To be included, patients had to have been on PD-1 monotherapy for the first time and have electively discontinued PD-1 inhibitors at 1 year in careful discussion with their treatment team. Among included patients, 25 percent (n=13) had complete response, 53.8 percent (n=28) had partial response, and 21.2 percent (n=11) had stable disease. They had a median age of 60.5 years and 26.9 percent were female. Median treatment duration was 11.1 months, (95% CI 10.5-11.4).


Patients were not included if they were on systemic therapies in addition to PD-1 inhibitors, or if they discontinued to PD-1 therapy due to toxicity or disease progression.


Median follow-up after treatment discontinuation was 20.5 months (range 3-49.2 months). Over this time period, 75 percent (n=39) of patients showed no evidence of disease progression (median progression-free survival not reached).


While 25 percent (n=13) of these patients progressed, these patients were able to be successfully re-treated. Median time to progression after treatment discontinuation was 3.9 months (range 0.7-30.9).


The median follow-up among those who progressed was 26.7 months (range 6.7-43.3 months). Over this time, five patients were able to go back on PD-1 therapy, and all five achieved disease control. Seven successfully received localized treatment to the site of progression (three received radiation and four underwent resection, followed by PD-1 inhibitors in two). One received BRAF/MEK followed by PD-1 inhibitor therapy.


Researchers plan to continue to follow these patients to find out whether disease control remains durable. They would like to find out what characteristics identify patients who are at increased risk of relapse upon PD-1 discontinuation.


"We have done a comprehensive analysis to see whether we could figure out any differences in the characteristics of the relapsed and non-relapsed patients," said Swami. "So far, they seem to be very much similar in their mutation profiles, age, and other prognostic markers."


The study was a retrospective, single-center analysis using real-world observational data. Results will need confirmation by larger, randomized clinical trials. Such trials, such as the STOP GAP trial, are already under way, but results may not be available for at least a few more years.


Veronica Hackethal is a contributing writer.