Nivolumab induced a greater rate of overall response than chemotherapy in patients with metastatic melanoma who progressed on or after anti-CTLA–4 therapy or treatment with BRAF inhibitors, according to phase 3 study results presented at the European Society for Medical Oncology Annual Congress in Madrid.
“For those who failed [on] ipilimumab (Yervoy, Bristol-Myers Squibb) and a BRAF inhibitor, there are no therapies known to prolong survival,” researcher Jeffrey Weber, MD, PhD, director of the Donald A. Adam Comprehensive Melanoma Research Center of Excellence Moffitt Cancer Center in Tampa, Fla., told HemOnc Today. “This is the first phase 3 study of a PD-1 inhibitor, and first evidence that a PD-1 inhibitor is superior to any other therapy for ipilimumab-refractory melanoma.”
The analysis included 370 patients. Weber and colleagues assigned 268 of them to receive 3 mg/kg nivolumab (Opdivo, Bristol-Myers Squibb) every 2 weeks. The 102 patients in the control arm received investigator’s choice chemotherapy, which included dacarbazine or carboplatin plus paclitaxel.
The overall response rate analysis was planned after a follow-up of at least 6 months. By that time, 120 patients had been treated in the nivolumab arm, and 47 patients had been treated in the chemotherapy arm.
Overall, 32% (95% CI, 24-41; n=38) of patients assigned nivolumab responded to treatment, compared with 11% (95% CI, 3.5-23; n=5) of patients assigned chemotherapy.
The median time to response was 2.1 months (95% CI, 1.6-7.4) in the nivolumab arm and 3.5 months (95% CI, 2.1-6.1) in the chemotherapy arm.
Thirty-six patients assigned nivolumab were still responding to treatment at the time of the analysis. The median duration of response was not reached in this cohort (range, 1.4+ to 10+ months). Four patients assigned chemotherapy were still responding at the time of analysis, with a median response duration of 3.6 months (range, 1.3+ to 3.5).
Among all responders, a greater proportion of those assigned nivolumab experienced a ≥50% reduction in target lesion burden (82% vs. 60%).
An additional ten patients assigned nivolumab demonstrated an immune-related response, or a ≥30% reduction in target lesion tumor burden.
Researchers reported a higher incidence of grade 3 and grade 4 adverse events (31% vs. 9%) and a higher discontinuation rate due to adverse events (7.8% vs. 2.2%) in the chemotherapy arm.
“It is surprising how good the data look in favor of the PD-1 immunotherapy from all angles,” Weber said.
The next step will be to conduct research designed to evaluate proper ways to combine nivolumab with other agents, Weber said.
For more information:
Weber J. Abstract #LBA3_PR. Presented at: European Society for Medical Oncology Annual Congress; Sept. 26-30, 2014; Madrid.
Disclosure: Weber reports advisory board roles with and research funding from Bristol-Myers Squibb, Genentech and Merck. See the abstract for a list of the other researchers’ relevant financial disclosures.