In the phase III OAK trial reported in The Lancet by Achim Rittmeyer, MD, of Lungenfachklinik Immenhausen, Germany, and colleagues, treatment with the anti–programmed cell death ligand 1 (PD-L1) antibody atezolizumab (Tecentriq) improved overall survival vs docetaxel in previously treated non–small cell lung cancer (NSCLC).¹ Results of the trial supported the recent approval of atezolizumab in metastatic NSCLC in patients who have received prior platinum-containing therapy.

Study Details

In this open-label trial, 1,225 patients were recruited from 194 sites in 31 countries between March 2014 and April 2015. The primary efficacy analysis was performed in the first 850 patients; in this population, 425 patients were randomized to receive atezolizumab at 1,200 mg or docetaxel at 75 mg/m² every 3 weeks.

These clinically relevant data support atezolizumab as a new treatment option for patients with advanced NSCLC whose disease has progressed during or after platinum-based chemotherapy.

— Achim Rittmeyer, MD, and colleagues

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Patients had squamous or nonsquamous disease, measurable disease, and an Eastern Cooperative Oncology Group performance status of 0 or 1. They also had received one to two previous cytotoxic chemotherapy regimens, including one or more platinum-based combination therapies for stage IIIB or IV disease. Patients with a history of autoimmune disease and those who had received previous docetaxel, CD137 agonists, anti–cytotoxic T-lymphocyte–associated protein 4 (CTLA-4), or treatment targeting the PD-L1 and programmed cell death protein 1 (PD-1) pathway were excluded. The coprimary endpoints were overall survival in the intention-to-treat population and in the populations with ≥ 1% PD-L1 expression on tumor cells (TC) or tumor-infiltrating immune cells (IC), defined as the TC1/2/3 or IC1/2/3 populations, respectively.

Improved Overall Survival

Median follow-up was 21 months at the primary analysis. Among all patients in the primary analysis intent-to-treat population, median overall survival was 13.8 months (95% confidence interval [CI] = 11.8–15.7 months) in the atezolizumab group vs 9.6 months (95% CI = 8.6–11.2 months) in the docetaxel group (hazard ratio [HR] = 0.73, P = .0003). In the TC1/2/3 or IC1/2/3 population, median overall survival was 15.7 months (95% CI = 12.6–18.0 months) among 241 patients receiving atezolizumab vs 10.3 months (95% CI = 8.8–12.0 months) among 222 patients receiving docetaxel (HR = 0.74, P = .0102).

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% 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.

Adverse Events

Among the total of 1,225 randomized patients, 609 receiving atezolizumab and 578 receiving docetaxel constituted the safety population. The most common adverse events of any grade that were ≥ 5% more common with atezolizumab were musculoskeletal pain and pruritus; those side effects more common with docetaxel included fatigue, alopecia, diarrhea, and anemia. 

Treatment-related adverse events of any grade occurred in 64% of the atezolizumab group vs 86% of 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 atezolizumab patients included pneumonitis (6 patients [1%] any grade; 4 patients grade 3), hepatitis (2 patients [< 1%], both grade 3), and colitis (2 patients [< 1%], both grade 2). Adverse events led to treatment discontinuation in 8% vs 19% of patients. Treatment-related death occurred in one patient in the docetaxel group.

The investigators concluded: “[T]his phase III study of a PD-L1–directed antibody, atezolizumab, shows a clinically meaningful survival benefit over docetaxel in previously treated patients with NSCLC regardless of PD-L1 expression or histology, with a favorable safety profile compared with docetaxel. These clinically relevant data support atezolizumab as a new treatment option for patients with advanced NSCLC whose disease has progressed during or after platinum-based chemotherapy.” ■

Disclosure: The study was funded by F. Hoffmann-La Roche and Genentech. For full disclosures of the study authors, visit www.the lancet.com.

Reference

1. Rittmeyer A, Barlesi F, Waterkamp D, et al: Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): A phase 3, open-label, multicentre randomised controlled trial. Lancet 389:255-265, 2017.