In a retrospective analysis reported in JAMA Oncology, Long et al found that a substantial proportion of patients with advanced melanoma derived benefit from continued nivolumab (Opdivo) treatment after Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1–defined disease progression.
The study involved pooled data from the phase III CheckMate 066 and 067 trials in treatment-naive patients with advanced disease. In the trials, patients received nivolumab at 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity; patients could be treated beyond disease progression at investigator’s discretion if they were deriving apparent clinical benefit and tolerating treatment. Patients receiving treatment for ≥ 6 weeks beyond disease progression were considered to have received treatment beyond disease progression. Data analysis was conducted between November 2015 and January 2017.
Treatment Beyond Disease Progression
Among 526 randomized patients (median age = 62 years, 61% male), 306 (58%) had disease progression; of them, 85 (28%) were treated beyond disease progression (TBP group), and 221 (72%) stopped treatment before or at disease progression (no-TBP group). Among TBP patients, 24 (28%) had a target lesion reduction > 30% from baseline after disease progression (TBP > 30% group). At the time of analysis, 65 TBP patients (76%) and 21 TBP >30% patients (87%) were still alive, with 27 (32%) and 11 (46%) continuing to receive treatment.
Median time from disease progression to the last dose of treatment was 4.7 months (range = 1.4–25.8 months) for TBP patients and 7.6 months (range = 2.4–19.4 months) for TBP > 30% patients. Median time from disease progression to > 30% tumor reduction was 1.4 months (range = 0.2–7.0 months). Median overall survival from randomization was not reached in the TBP group and 10.6 months in the no-TBP group, with 24-month survival rates of 59% and 25%. Treatment-related grade 3 or 4 adverse events with a potential immunologic cause occurred in 6% of TBP patients and 4% of no-TBP patients.
The investigators concluded: “A substantial proportion of selected patients treated with front-line nivolumab who were clinically stable and judged to be eligible for treatment beyond [Response Evaluation Criteria in Solid Tumors version 1.1]–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.”
The study was funded by Bristol-Myers Squibb.
Georgina V. Long, MBBS, PhD, of the Melanoma Institute Australia, North Sydney, is the corresponding author of the JAMA Oncology article.
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