Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer¶
Why this mattered¶
TBD
Abstract¶
BACKGROUND: Nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, disrupts PD-1-mediated signaling and may restore antitumor immunity. METHODS: In this randomized, open-label, international phase 3 study, we assigned patients with nonsquamous non-small-cell lung cancer (NSCLC) that had progressed during or after platinum-based doublet chemotherapy to receive nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks or docetaxel at a dose of 75 mg per square meter of body-surface area every 3 weeks. The primary end point was overall survival. RESULTS: Overall survival was longer with nivolumab than with docetaxel. The median overall survival was 12.2 months (95% confidence interval [CI], 9.7 to 15.0) among 292 patients in the nivolumab group and 9.4 months (95% CI, 8.1 to 10.7) among 290 patients in the docetaxel group (hazard ratio for death, 0.73; 96% CI, 0.59 to 0.89; P=0.002). At 1 year, the overall survival rate was 51% (95% CI, 45 to 56) with nivolumab versus 39% (95% CI, 33 to 45) with docetaxel. With additional follow-up, the overall survival rate at 18 months was 39% (95% CI, 34 to 45) with nivolumab versus 23% (95% CI, 19 to 28) with docetaxel. The response rate was 19% with nivolumab versus 12% with docetaxel (P=0.02). Although progression-free survival did not favor nivolumab over docetaxel (median, 2.3 months and 4.2 months, respectively), the rate of progression-free survival at 1 year was higher with nivolumab than with docetaxel (19% and 8%, respectively). Nivolumab was associated with even greater efficacy than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression (≥1%, ≥5%, and ≥10%) of the PD-1 ligand. Treatment-related adverse events of grade 3 or 4 were reported in 10% of the patients in the nivolumab group, as compared with 54% of those in the docetaxel group. CONCLUSIONS: Among patients with advanced nonsquamous NSCLC that had progressed during or after platinum-based chemotherapy, overall survival was longer with nivolumab than with docetaxel. (Funded by Bristol-Myers Squibb; CheckMate 057 ClinicalTrials.gov number, NCT01673867.).
Related¶
- cite → Pembrolizumab for the Treatment of Non–Small-Cell Lung Cancer — The nivolumab lung-cancer trial links to pembrolizumab through clinical PD-1 checkpoint blockade as a therapeutic strategy in non-small-cell lung cancer.
- cite → Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer — The nivolumab trial cites mutational-landscape work because tumor mutational burden was proposed as a predictor of sensitivity to PD-1 blockade in non-small-cell lung cancer.
- cite → Improved Survival with Ipilimumab in Patients with Metastatic Melanoma — The nivolumab trial cites ipilimumab survival data as precedent that immune checkpoint inhibition can improve overall survival in advanced cancer.
- cite → Nivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer — The nonsquamous nivolumab study is paired with the squamous-cell trial to compare nivolumab versus docetaxel across major histologic subtypes of advanced non-small-cell lung cancer.
- cite → Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in Cancer — The nivolumab phase 3 trial builds on the 2012 anti-PD-1 study that established early safety, antitumor activity, and immune correlates for PD-1 blockade.
- cite ← Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer — The 2018 trial cites nivolumab evidence showing PD-1 blockade improves survival versus docetaxel in previously treated nonsquamous NSCLC.
- cite ← Pembrolizumab for the Treatment of Non–Small-Cell Lung Cancer — Both studies test PD-1 pathway blockade in advanced nonsquamous non-small-cell lung cancer, comparing pembrolizumab evidence with nivolumab survival results.
- enables ← Improved Survival with Ipilimumab in Patients with Metastatic Melanoma — The ipilimumab melanoma trial enables the nivolumab lung-cancer trial by clinically validating immune-checkpoint blockade as an anticancer strategy.