In an analysis of the phase III CheckMate 017 and 057 trials in previously treated patients with advanced squamous (017) and nonsquamous (057) non–small cell lung cancer (NSCLC), reported in the Journal of Clinical Oncology, Hossein Borghaei, DO, MS, and colleagues found pooled 5-year overall survival rates of 13.4% vs 2.6% for nivolumab vs docetaxel.
Primary analyses in both trials showed improved overall survival with nivolumab vs docetaxel.
Study Details
The pooled analysis consisted of 854 patients whose disease progressed after first-line platinum-based chemotherapy, including nivolumab vs docetaxel randomly assigned groups of 135 vs 137 in CheckMate 017 and 292 vs 290 in CheckMate 057. Patients received nivolumab at 3 mg/kg once every 2 weeks or docetaxel at 75 mg/m2 once every 3 weeks until disease progression or unacceptable toxicity in both trials. The primary endpoint for both trials was overall survival.
“At 5 years, nivolumab continued to demonstrate a survival benefit vs docetaxel, exhibiting a five-fold increase in overall survival, with no new safety signals. These data represent the first report of 5-year outcomes from randomized phase III trials of a PD-1 inhibitor in previously treated advanced NSCLC.”— Hossein Borghaei, DO, MS
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Key Findings
Minimum follow-up was 64.2 and 64.5 months for CheckMate 017 and 057, respectively, and median follow-up was 69.5 months and 69.4 months.
In the pooled population, 50 of 427 nivolumab-treated patients and 9 of 427 docetaxel-treated patients remained alive at time of analysis, with 5-year overall survival of 13.4% vs 2.6%. Median overall survival was 11.1 vs 8.1 months (hazard ratio = 0.68, 95% confidence interval = 0.59–0.78).
Five-year overall survival was 12.3% vs 3.6% among patients with squamous histology and 14.0% vs 2.1% among those with nonsquamous histology. Rates were 18.3% vs 3.4% among patients with PD-L1 expression ≥ 1% and 8.0% vs 2.0% among those with expression < 1%.
Progression-free survival at 5 years was 8.0% vs 0%.
In landmark analysis, nivolumab-treated patients who were progression-free at 2 years (n = 45), 3 years (n = 29), and 4 years (n = 25) had 59.6%, 78.3%, and 87.5% probabilities of being progression-free at 5 years and 82.0%, 93.0%, and 100.0% probabilities of survival at 5 years. Among docetaxel-treated patients, those who were progression-free at 2 years (n = 4) and 3 years (n = 1; none were progression-free at 4 years) had a 0% probability of being progression-free or surviving at 5 years.
Treatment-related adverse events (n = 13) were reported in 8 (25.8%) of 31 nivolumab-treated patients between 3 and 5 years of follow-up, with 7 experiencing new adverse events. All adverse events were grade 1 or 2, except for one grade 3 event (increased lipase). In addition to the grade 3 event, adverse events consisted of two cases of diarrhea and one case each of asthenia, rash, pruritus, erythema, hypophosphatemia, skin exfoliation, nummular eczema, memory impairment, state of confusion, and hot flush.
The investigators concluded, “At 5 years, nivolumab continued to demonstrate a survival benefit vs docetaxel, exhibiting a five-fold increase in overall survival, with no new safety signals. These data represent the first report of 5-year outcomes from randomized phase III trials of a PD-1 inhibitor in previously treated advanced NSCLC.”
Dr. Borghaei, of Fox Chase Cancer Center, 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.
