Nivolumab for Patients With Advanced Melanoma Treated Beyond Progression: Analysis of 2 Phase 3 Clinical Trials.

Autor:	Long GV; Melanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia.; Mater Hospital, North Sydney, New South Wales, Australia., Weber JS; Department of Medical Oncology, Moffitt Cancer Center, Tampa, Florida.; now with Department of Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York., Larkin J; Department of Oncology, Royal Marsden Hospital, London, United Kingdom., Atkinson V; Gallipoli Medical Research Foundation and Princess Alexandra Hospital, and University of Queensland, Queensland, Australia., Grob JJ; Department of Dermatology and Skin Cancer, Hospital Timone APHM, Aix-Marseille University, Marseille, France., Schadendorf D; Department of Skin, University Hospital Essen, Essen, Germany.; Department of Urology, University Hospital Essen, Essen, Germany., Dummer R; Department of Dermatology, UniversitaetsSpital, Zurich, Switzerland., Robert C; Department of Medicine Institute Gustave Roussy, Gustave Roussy and Paris-Sud University, Villejuif Paris-Sud, France., Márquez-Rodas I; Servicio de Oncología Médica, Hospital General Universitario Gregorio Marañón, Madrid, Spain., McNeil C; Chris O'Brien Lifehouse, Melanoma Institute Australia, Camperdown, New South Wales, Australia.; Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia., Schmidt H; Department of Oncology, Aarhus University Hospital, Aarhus, Denmark., Briscoe K; Department of Medical Oncology, Coffs Harbour Health Campus, New South Wales, Australia., Baurain JF; Melanoma Clinic at King Albert II Cancer Institute, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Bruxelles, Belgium., Hodi FS; Melanoma Center and Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., Wolchok JD; Ludwig Center for Cancer Immunotherapy at Memorial Sloan Kettering Cancer Center, New York, New York.
Jazyk:	angličtina
Zdroj:	JAMA oncology [JAMA Oncol] 2017 Nov 01; Vol. 3 (11), pp. 1511-1519.
DOI:	10.1001/jamaoncol.2017.1588
Abstrakt:	Importance: Immune checkpoint inhibitors have demonstrated atypical response patterns, which may not be fully captured by conventional response criteria. There is a need to better understand the potential benefit of continued immune checkpoint inhibition beyond progression. Objective: To evaluate the safety and potential benefit of nivolumab (anti-programmed cell death receptor 1) monotherapy beyond Response Evaluation Criteria in Solid Tumors (RECIST) v1.1-defined progression. Design, Setting, and Participants: Pooled, retrospective analysis of data from phase 3 trials of nivolumab in treatment-naive patients with advanced melanoma (CheckMate 066 or CheckMate 067) conducted at academic and clinical cancer centers. Participants were patients treated beyond first disease progression, defined as those who received their last dose of nivolumab more than 6 weeks after progression (TBP group); and patients not treated beyond progression, who discontinued nivolumab therapy before or at progression (non-TBP group). Data analyses were conducted from November 6, 2015, to January 11, 2017. Interventions: Nivolumab (3 mg/kg every 2 weeks) administered until progression or unacceptable toxic effects. Patients could be treated beyond progression if deriving apparent clinical benefit and tolerating study drug, at the investigator's discretion. Main Outcomes and Measures: Tumor response and safety in TBP and non-TBP patients. Results: Among 526 randomized patients (39% [n = 203] female; median age, 62 years [range, 18-90 years]), 306 (58%) experienced disease progression, including 85 (28%) TBP patients and 221 (72%) non-TBP patients. Twenty-four (28%) of the TBP patients had a target lesion reduction of greater than 30% after progression compared with baseline (TBP>30% group). At the time of this analysis, 65 (76%) TBP patients and 21 (87%) TBP>30% patients were still alive; 27 (32%) and 11 (46%), respectively, continued to receive treatment. Median (range) time from progression to last dose of treatment was 4.7 (1.4-25.8) months for TBP patients and 7.6 (2.4-19.4) months for TBP>30% patients. Median (range) time from progression to greater than 30% tumor reduction was 1.4 (0.2-7.0) months. Treatment-related select grade 3 to 4 adverse events were similar in the TBP and non-TBP groups (5 [6%] and 9 [4%], respectively). Conclusions and Relevance: A substantial proportion of selected patients treated with frontline nivolumab who were clinically stable and judged to be eligible for treatment beyond RECIST v1.1-defined progression by the treating investigators derived apparent clinical benefit without compromising safety. Further analysis will help define the potential benefit of continued nivolumab treatment beyond progression. Trial Registration: clinicaltrials.gov Identifiers: NCT01721772 (CheckMate 066) and NCT01844505 (CheckMate 067).
Databáze:	MEDLINE
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