Advanced melanoma and nivolumab

How Effective Is Nivolumab Beyond Progression in Advanced Melanoma?

A retrospective analysis of two phase III clinical trials published recently in JAMA Oncology has found that treatment of advanced melanoma with nivolumab beyond first disease progression resulted in continued reduction of tumor lesion size in 28% of patients, without significant increase in treatment-related adverse events (AEs). The study pooled results from 526 patients with advanced, treatment-naïve melanoma who were treated with nivolumab (3 mg/kg every 2 weeks) from two clinical trials (CheckMate 066 and CheckMate 067). Patients in these trials who experienced disease progression by RECIST v1.1 criteria could continue treatment if they were deriving apparent clinical benefit, at the study investigator’s discretion.

A total 306 patients (58%) experienced disease progression on study, including 85 patients who were treated beyond progression (TBP; ie, those who received their last dose of nivolumab more than 6 weeks after progression). Of the patients in the TBP group, 28% (24/85) had a target lesion reduction of greater than 30% after progression compared with baseline (TBP >30% group). Patients who achieved a reduction in their tumor volume after initial disease progression did so before week 24. At the time of this analysis, 76% of patients in the TBP group were alive, with 32% continuing treatment. In the TBP >30% group, 87% were alive at the time of analysis, and 46% were continuing treatment.

Grade 3/4 treatment-related AEs were similar in the TBP group compared with patients who were not treated beyond progression (non-TBP). The TBP group experienced increases in any grade skin (51% vs 26% non-TBP), gastrointestinal (21% vs 14%), and endocrine (15% vs 8%) toxicities.

The study investigators concluded that these results suggest that continued treatment with nivolumab beyond first progression may be a viable option in some patients, and that future studies should be directed toward confirming these data and identifying factors that may help identify appropriate patients for this treatment approach. In an accompanying commentary, the authors suggested that these results could be seen as either “glass half full” or “glass half empty” findings. Looking at the findings from a more pessimistic view, they may indicate that while the continued response without additional toxicity in patients treated beyond progression was promising, the relatively small number of patients in which this strategy worked (only 5% of the total population) suggests a limited benefit and potential harms (eg, increased risk of toxicity, increased costs, risk of forgoing or delaying switch to another, more effective agent). The commentary authors suggest that future studies should be directed toward determining the optimal duration of treatment with immune checkpoint inhibitors and the relative benefits of treating beyond progression versus switching to an alternate therapy at progression; and evaluating whether patients need to be treated to progression or simply to best response with treatment rechallenge at progression.


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