Atezolizumab vs Docetaxel in Patients With Previously Treated NSCLC (OAK): A Phase 3, Open-Label, Multicentre Randomised Controlled Trial
Posted: Monday, December 12, 2016
Results of the phase 3 OAK trial support the late 2016 approval of atezolizumab in patients with metastatic NSCLC who have received prior platinum-containing therapy: treatment with the anti–programmed cell death ligand 1 (PD-L1) antibody improved overall survival vs docetaxel, regardless of PD-L1 expression or histology, with a favorable safety profile.
The co-primary endpoints were overall survival in the intention-to-treat population and in the population with ≥ 1% PD-L1 expression on tumor cells or tumor-infiltrating immune cells.
Among all patients in the primary analysis of the intention-to-treat population, median overall survival was 13.8 months in the atezolizumab group vs 9.6 months in the docetaxel group (hazard ratio [HR] = 0.73, P = .0003).
Median overall survival was also improved with atezolizumab among patients with low or undetectable PD-L1 expression (12.6 months vs 8.9 months, HR = 0.75, 95% confidence interval [CI] = 0.59–0.96). Among 112 atezolizumab patients and 110 docetaxel patients with squamous histology, median overall survival was 8.9 vs 7.7 months (HR = 0.73, 95% CI = 0.54–0.98). Among 313 and 315 patients with nonsquamous histology, median overall survival was 15.6 vs 11.2 months (HR = 0.73, 95% CI = 0.60–0.89).
Median progression-free survival was 2.8 months in the atezolizumab group vs 4.0 months in the docetaxel group (HR = 0.95, 95% CI = 0.82–1.10). Objective response was observed in 14% vs 13%; median duration of response was 16.3 vs 6.2 months.
The most common adverse events of any grade that were ≥ 5% more common with atezolizumab were musculoskeletal pain and pruritus; those adverse events more common with docetaxel included fatigue, alopecia, diarrhea, and anemia. Treatment-related adverse events of any grade occurred in 64% of those in the atezolizumab group vs 86% of those in the docetaxel group, with the most common in the atezolizumab group being fatigue (14%), nausea (9%), decreased appetite (9%), and asthenia (8%). Grade 3 or 4 adverse events occurred in 37% of atezolizumab patients vs 54% of docetaxel patients and were considered related to treatment in 15% vs 43%.
Serious adverse events occurred in 32% vs 31%. Immune-mediated adverse events in patients treated with atezolizumab included pneumonitis hepatitis, and colitis. Adverse events led to treatment discontinuation in 8% vs 19% of patients. Treatment-related death occurred in one patient in the docetaxel group.