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Safety Profile of Nivolumab Monotherapy in Advanced Melanoma

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Key Points

  • Treatment-related potential immune-related adverse events of any grade occurred in 49% of patients receiving nivolumab for advanced melanoma, with 3.6% having grade 3 or 4 adverse events.
  • Treatment-related adverse events led to nivolumab discontinuation in 3.0% of patients.

As reported in the Journal of Clinical Oncology, Weber et al performed a pooled analysis of the safety profile of nivolumab (Opdivo) monotherapy in advanced melanoma, including a focus on potential immune-related (select) adverse events.

The analysis pooled safety data from 576 patients receiving nivolumab at 3 mg/kg once every 2 weeks in 4 studies, including 2 phase III trials. Among the 576 patients, 71% experienced any-grade treatment-related adverse events, with the most common being fatigue (25%), pruritus (17%), diarrhea (13%), and rash (13%); 10% had grade 3 or 4 treatment-related adverse events. Treatment-related adverse events led to treatment discontinuation in 3.0%. No drug-related deaths were reported.

Select Adverse Events

Treatment-related select adverse events of any grade occurred in 255 patients (49%), with the most common being those affecting the skin (34.0%) and gastrointestinal (GI) tract (13.4%). Grade 3 or 4 treatment-related select adverse events occurred in 3.6%, with the most common being GI and hepatic events (1.0% each). Median time to onset of select adverse events ranged from 5 weeks for skin to 15 weeks for renal events. A total of 114 of 474 patients (24%) in the 2 phase III trials received systemic immune-modulating agents to manage treatment-related adverse events of any kind, with resolution occurring in 58% of cases.

After adjustment for the number of doses, the objective response rate was higher among patients with any treatment-related select adverse event than those without (48.6% vs 17.8%, P < .001); among 18 patients with grade 3 or 4 select adverse events, the objective response rate was 27.8%.

In a landmark analysis excluding patients with disease progression before 12 weeks, median progression-free survival was 14.6 months among patients with any-grade select adverse events, 9.7 months among those with grade 3 or 4 select adverse events, and 15.6 months among all patients. The objective response rate was 29.8% in 114 patients receiving immune-modulating agents vs 31.8% in 462 patients not receiving immune-modulating agents.

The investigators concluded: “Treatment-related [adverse events] with nivolumab monotherapy were primarily low grade, and most resolved with established safety guidelines. Use of [immune-modulating agents] did not affect [the objective response rate], although treatment-related select [adverse events] of any grade were associated with [a] higher [objective response rate] but no progression-free survival benefit.”

The study was supported by Bristol-Myers Squibb and the Royal Marsden/Institute of Cancer Research Biomedical Research Centre for Cancer.

Jeffrey S. Weber, MD, PhD, of the NYU Langone Medical Center, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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