The 5-year outcomes of the CheckMate 066 trial, reported in the Journal of Clinical Oncology by Caroline Robert, MD, PhD, and colleagues, showed continued benefit of first-line nivolumab vs dacarbazine in advanced BRAF wild-type melanoma. The results add to data indicating that nivolumab can be associated with long-term survival in this setting.
Caroline Robert, MD, PhD
Study Details
In the double-blind trial, 418 patients with unresectable stage III/IV disease were randomly assigned to receive nivolumab at 3 mg/kg every 2 weeks (n = 210) or dacarbazine at 1,000 mg/m2 (n = 208) every 3 weeks. Treatment continued until disease progression or unacceptable toxicity. Treatment after disease progression was permitted for patients who continued to have clinical benefit. The primary endpoint was overall survival; secondary endpoints included progression-free survival and objective response rate.
In a 3-year analysis, median overall survival was 37.5 months in the nivolumab group vs 11.2 months in the dacarbazine group, with 3-year rates of 52% vs 22%.
Five-Year Outcomes
Patients were followed for a minimum of 60 months from the last patient randomly assigned in the trial. At 5 years, median overall survival was 37.3 months in the nivolumab group vs 11.2 months in the dacarbazine group (hazard ratio [HR] = 0.5, P < .0001), with 5-year rates of 39% vs 17%.
In subgroup analyses, overall survival at 5 years was 48% vs 24% among 244 patients with normal lactate dehydrogenase (LDH) and 27% vs 7% among 153 patients with LDH above the upper limit of normal. Overall survival at 5 years was 52% vs 17% among 120 patients with PD-L1 expression ≥ 5% (staining of ≥ 5% of tumor cells) and 34% vs 20% among 244 patients with PD-L1 expression < 5%.
KEY POINTS
- Overall survival at 5 years was 39% in the nivolumab group vs 17% in the dacarbazine group.
- Among 75 patients in the nivolumab group alive and evaluable at 5-year analysis, 83% had not received subsequent therapy, 23% were still on study treatment, and 60% were treatment-free.
In the nivolumab and dacarbazine groups, 48% and 65% of patients received subsequent systemic therapy. Among 71 patients in the nivolumab group who received subsequent therapy that included ipilimumab, 5-year overall survival was 13%. Overall survival at 5 years was 38% among 37 patients in the dacarbazine group who received subsequent therapy including nivolumab, and 23% among 91 patients who received subsequent therapy including ipilimumab.
Median progression-free survival was 5.1 months in the nivolumab group vs 2.2 months in the dacarbazine group (HR = 0.4, P < .0001), with 5-year rates of 28% vs 3%. Five-year rates were 43% vs 4% in patients with PD-L1 expression ≥ 5% and 21% vs 3% in patients with PD-L1 expression < 5%.
Among all patients, the objective response rates were 42% in the nivolumab group vs 14% in the dacarbazine group. Median duration of response was not reached in the nivolumab group vs 6 months in the dacarbazine group. Overall, 27 (30%) of 89 responders in the nivolumab group had a response lasting ≥ 60 months, with none of 30 responders in the dacarbazine group having a response that lasted ≥ 60 months.
Among 78 patients in the nivolumab group alive at 5 years, objective response had been achieved in 63 (81%). Among 33 patients in the dacarbazine group alive at 5 years, objective response had been observed in 13 (39%).
Among 42 patients in the nivolumab group who had a complete response, 37 (88%) were alive at 5 years; among 47 with a partial response, 26 (55%) were alive at 5 years. Among 75 patients in the nivolumab group alive and evaluable at 5-year analysis, 62 (83%) had not received subsequent therapy, 17 (23%) were still on study treatment, and 45 (60%) were treatment-free.
The investigators concluded, “Results from this 5-year analysis confirm the significant benefit of nivolumab over dacarbazine for all endpoints and add to the growing body of evidence supporting long-term survival with nivolumab monotherapy. Survival is strongly associated with achieving a durable response, which can be maintained after treatment discontinuation, even without subsequent systemic therapies.”
Dr. Robert, of Institut Gustave Roussy, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Bristol Myers Squibb. For full disclosures of the study authors, visit ascopubs.org.
