Evaluation of Immune-Related Response Criteria and RECIST v1.1 in Patients With Advanced Melanoma Treated With Pembrolizumab

作者：F. Stephen Hodi, Wen-Jen Hwu, Richard Kefford, Jeffrey S. Weber, Adil Daud, Omid Hamid, Amita Patnaik, Antoni Ribas, Caroline Robert, Tara C. Gangadhar, Anthony M. Joshua, Peter Hersey, Roxana Dronca, Richard W. Joseph, Darcy A. Hille, Dahai Xue, Xiaoyun Li, Sunyu Kang, Scot Ebbinghaus, Andrea Perrone, Jedd D. Wolchok · 发表于：Journal of Clinical Oncology · 年份：2016 · DOI：10.1200/jco.2015.64.0391 · 被引用次数：754 · 研究领域：Cancer Immunotherapy and Biomarkers、Cutaneous Melanoma Detection and Management、Immunotherapy and Immune Responses

PURPOSE: We evaluated atypical response patterns and the relationship between overall survival and best overall response measured per immune-related response criteria (irRC) and Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) in patients with advanced melanoma treated with pembrolizumab in the phase Ib KEYNOTE-001 study (clinical trial information: NCT01295827). PATIENTS AND METHODS: Patients received pembrolizumab 2 or 10 mg/kg every 2 weeks or every 3 weeks. Atypical responses were identified by using centrally assessed irRC data in patients with ≥ 28 weeks of imaging. Pseudoprogression was defined as ≥ 25% increase in tumor burden at week 12 (early) or any assessment after week 12 (delayed) that was not confirmed as progressive disease at next assessment. Response was assessed centrally per irRC and RECIST v1.1. RESULTS: Of the 655 patients with melanoma enrolled, 327 had ≥ 28 weeks of imaging follow-up. Twenty-four (7%) of these 327 patients had atypical responses (15 [5%] with early pseudoprogression and nine [3%] with delayed pseudoprogression). Of the 592 patients who survived ≥ 12 weeks, 84 (14%) experienced progressive disease per RECIST v1.1 but nonprogressive disease per irRC. Two-year overall survival rates were 77.6% in patients with nonprogressive disease per both criteria (n = 331), 37.5% in patients with progressive disease per RECIST v1.1 but nonprogressive disease per irRC (n = 84), and 17.3% in patients with progressive disease per b...