Because of atypical responses, conventional Response Evaluation Criteria in Solid Tumors (RECIST) might underestimate the benefit of pembrolizumab in approximately 15% of patients treated for melanoma, a study published in the Journal of Clinical Oncology has shown.1
For the study, researchers sought to evaluate atypical response patterns and the association between overall survival and best overall response measured per immune-related response criteria (irRC) and RECIST version 1.1 in patients with advanced melanoma treated with pembrolizumab.
Investigators analyzed data from the phase 1b KEYNOTE-001 study, which enrolled 655 patients with melanoma. Participants received pembrolizumab 2 or 10 mg/kg IV every 2 or 3 weeks.
Atypical responses were identified by using centrally assessed irRC data in patients with 28 or more weeks of imaging. Pseudoprogression was defined as an early 25% or greater increase in tumor burden at week 12 or any delayed assessment after week 12 that was not confirmed as progressive disease at next assessment. Investigators centrally assessed response per irRC and RECIST version 1.1.
Of the 655 patients, 327 had 28 or more weeks of imaging follow-up. Results showed that 7% of those experienced atypical responses, of which 5% had early pseudoprogression and 3% had delayed pseudoprogression.
Researchers found that of the 592 patients who survived 12 weeks or more, 14% experienced progressive disease per RECIST version 1.1 but nonprogressive disease per irRC.
Further, the study demonstrated that 2-year overall survival rates were 77.6% in patients with nonprogressive disease per both criteria, 37.5% in patients with progressive disease per RECIST version 1.1 but nonprogressive disease per irRC, and 17.3% in patients with progressive disease per both criteria.
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The findings suggested that modified criteria that allow for treatment beyond initial disease progression per RECIST version 1.1 might prevent premature treatment discontinuation.
- Hodi FS, Hwu W-J, Kefford R, et al. Evaluation of immune-related response criteria and RECIST v1.1 in patients with advanced melanoma treated with pembrolizumab [published online ahead of print March 7, 2016]. J Clin Oncol. doi: 10.1200/JCO.2015.64.0391.