Can patients with treatment-naive advanced melanoma derive apparent clinical benefit from nivolumab treatment beyond Response Evaluation Criteria in Solid Tumors (RECIST) v1.1-defined progression without compromising safety?
In this pooled, retrospective analysis of 85 treatment-naive patients with advanced melanoma who continued nivolumab treatment beyond RECIST v1.1-defined progression in phase 3 clinical trials (CheckMate 066, CheckMate 067), 28% had a target lesion reduction of greater than 30% after progression compared with baseline, with no new or unexpected adverse events.
Continued treatment with nivolumab may be an option to achieve further benefit without compromising safety in some patients with advanced melanoma.
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.
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.
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.
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.
clinicaltrials.gov Identifiers: NCT01721772 (CheckMate 066) and NCT01844505 (CheckMate 067)
Long GV, Weber JS, Larkin J, Atkinson V, Grob J, Schadendorf D, Dummer R, Robert C, Márquez-Rodas I, McNeil C, Schmidt H, Briscoe K, Baurain J, Hodi FS, Wolchok JD. Nivolumab for Patients With Advanced Melanoma Treated Beyond ProgressionAnalysis of 2 Phase 3 Clinical Trials. JAMA Oncol. Published online June 29, 2017. doi:10.1001/jamaoncol.2017.1588