Assessment of Survival Impact of Atypical Responses With Pembrolizumab Treatment in Advanced Melanoma
As reported by Hodi et al in the Journal of Clinical Oncology, use of conventional Response Evaluation Criteria in Solid Tumors (RECIST) to assess response may have underestimated the benefit of treatment with the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab (Keytruda) in the KEYNOTE-001 study in advanced melanoma.
Study Details
The study evaluated atypical response patterns and the relationship between overall survival and response according to immune-related response criteria and RECIST v1.1 in patients receiving pembrolizumab. Atypical responses were identified via centrally assessed immune-related response criteria data in patients with ≥ 28 weeks of imaging. Pseudoprogression was defined as ≥ 25% increase in tumor burden at week 12 (early) or at any assessment after week 12 (delayed) that was not confirmed as progressive disease at the next assessment.
Association With Survival
Among 327 patients with ≥ 28 weeks of imaging follow-up, 24 (7%) had atypical responses, including 15 (5%) with early pseudoprogression and 9 (3%) with delayed pseudoprogression. Of 592 patients who survived ≥ 12 weeks, 84 (14%) had progressive disease on RECIST v1.1 but nonprogressive disease on immune-related response criteria.
Two-year overall survival was 77.6% in 331 patients with nonprogressive disease on both criteria, 37.5% in the 84 patients with progressive disease on RECIST but nonprogressive disease on immune-related response criteria, and 17.3% in 177 patients with progressive disease on both. Median overall survival was not reached, 22.5 months, and 8.4 months, respectively.
The investigators concluded: “Atypical responses were observed in patients with melanoma treated with pembrolizumab. Based on survival analysis, conventional RECIST might underestimate the benefit of pembrolizumab in approximately 15% of patients; modified criteria that permit treatment beyond initial progression per RECIST v1.1 might prevent premature cessation of treatment.”
The study was supported by Merck & Co.
F. Stephen Hodi, MD, of Dana-Farber Cancer Institute, is the corresponding author of the Journal of Clinical Oncology article.
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