First PD-L1 Inhibitor Approved as Second-Line Treatment for NSCLC

Atezolizumab (Tecentriq), a monoclonal antibody that inhibits the programmed death ligand-1 (PD-L1) protein, has been approved for the treatment of patients whose non-small cell lung cancer (NSCLC) failed to respond to treatment with platinum-based chemotherapy. Notably, the treatment was administered regardless of PD-L1 expression in the patient’s tumor.

The approval follows an FDA review of results from the phase 3 OAK and phase 2 POPLAR trials. OAK—a global, multicenter, open-label, randomized study—evaluated atezolizumab against docetaxel in 1225 patients with advanced or metastatic NSCLC who had failed on platinum-based chemotherapy. Patients with squamous and non-squamous form of the disease were randomized to receive intravenous atezolizumab at 1200 mg every 3 weeks, or intravenous docetaxel at 75 mg/m², every 3 weeks. The median overall survival (OS) following primary analysis in 850 patients was 13.8 (range, 11.8-15.7) months in the atezolizumab-treated cohort, compared with 9.6 (range, 8.6-11.2) months in the docetaxel-treated cohort (hazard ratio [HR], 0.74; P = .0004).

The POPLAR study—a global, multicenter open-label, randomized phase 2 study compared response to docetaxel versus atezolizumab in patients with previously treated locally advanced or metastatic NSCLC. The trial measured OS as the primary endpoint and progression-free survival (PFS), objective response rate (ORR), and safety as secondary endpoints. The median OS for patients in the atezolizumab arm was 12.6 (range, 9.7-16.0) months compared with 9.7 (range, 8.6-12.0) months following docetaxel treatment (HR, 0.69).

The most common (greater than or equal to 20%) adverse reactions with atezolizumab were fatigue, decreased appetite, dyspnea, cough, nausea, musculoskeletal pain, and constipation. The most common (greater than or equal to 2%) grade 3-4 adverse events in patients treated with atezolizumab were dyspnea, pneumonia, hypoxia, hyponatremia, fatigue, anemia, musculoskeletal pain, AST increase, ALT increase, dysphagia, and arthralgia. Clinically significant immune-related adverse events for patients receiving atezolizumab included pneumonitis, hepatitis, colitis, and thyroid disease.

“Tecentriq is a new option to help people with this type of previously treated metastatic lung cancer, regardless of PD-L1 expression, live longer than chemotherapy,” Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech, the company that developed the drug, said in a statement. “Tecentriq is the first and only approved cancer immunotherapy designed to target the PD-L1 protein, which may play an important role in the way the medicine works.”

The drug continues to be evaluated as first-line treatment for lung cancer, alone or as part of a combination regimen.