In a pooled analysis of long-term outcomes reported in the Journal of Clinical Oncology, Long et al found that nivolumab plus ipilimumab was associated with better overall survival vs nivolumab monotherapy in immune checkpoint inhibitor treatment–naive patients with unresectable or metastatic melanoma.
Study Details
The study involved pooled long-term data from six CheckMate studies in immune checkpoint inhibitor treatment–naive patients receiving nivolumab at 1 mg/kg plus ipilimumab at 3 mg/kg; nivolumab at 3 mg/kg plus ipilimumab at 1 mg/kg; or nivolumab monotherapy at 3 mg/kg. The primary outcome measure for the analysis was overall survival.
Key Findings
Median follow-up for overall survival was 45.0 months among 839 patients receiving nivolumab plus ipilimumab and 35.8 months among 536 receiving nivolumab monotherapy.
Overall survival was prolonged with nivolumab plus ipilimumab vs nivolumab monotherapy (hazard ratio [HR] = 0.78, 95% confidence interval [CI] = 0.67–0.91). Median overall survival was 84.6 vs 36.9 months, with 6-year rates of 52% vs 41%. Median melanoma-specific survival was not reached vs 44.8 months (HR = 0.70, 95% CI = 0.60–0.83).
At least numeric overall survival benefit of nivolumab plus ipilimumab vs nivolumab monotherapy was observed in BRAF-mutant disease (median = not reached vs 49.4 months, 6-year rate = 54% vs 44%; HR = 0.75, 95% CI = 0.54–1.03) and BRAF wild-type disease (median = 72.1 vs 36.0 months, 6-year rate = 50% vs 40%; HR = 0.82, 95% CI = 0.68–0.97); patients with normal (HR = 0.76, 95% CI = 0.62–0.93) and elevated lactate dehydrogenase (LDH; HR = 0.75, 95% CI = 0.60–0.94); and patients with PD-L1 expression < 1% (median = 46.8 vs 25.8 months, 6-year rate = 46% vs 33%; HR = 0.72, 95% CI = 0.56–0.91) and PD-L1 expression ≥ 1% (median = not reached vs 57.5 months, 6-year rate = 54% vs 48%; HR = 0.90, 95% CI = 0.72–1.11).
Factors associated with decreased overall survival were LDH > upper limit of normal with either treatment, age ≥ 65 years with nivolumab plus ipilimumab, and presence of liver metastases with nivolumab monotherapy.
The investigators concluded: “In this large, pooled nonrandomized retrospective analysis, we observed that [nivolumab plus ipilimumab] provides longer [overall survival] than [nivolumab] in patients with [immune checkpoint inhibitor] treatment–naïve advanced melanoma and identifies clinical factors that appear to be associated with survival for each treatment, which may assist with treatment decision making.
Georgina V. Long, PhD, MBBS, FRACP, of Melanoma Institute Australia and Royal North Shore and Mater Hospitals, The University of Sydney, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Bristol Myers Squibb and others. For full disclosures of the study authors, visit ascopubs.org.
