On May 18, 2020, the FDA approved a new indication for atezolizumab (Tecentriq; Genentech), a PD-L1 inhibitor, for the first-line treatment of adults with metastatic non–small-cell lung cancer (NSCLC) whose tumor has high PD-L1 expression (PD-L1 stained ≥50% of tumor cells [TC ≥50%] or PD-L1 stained tumor-infiltrating immune cells [IC] covering ≥10% of the tumor area [IC ≥10%]), and no EGFR or ALK genomic aberrations, as determined by an FDA-approved test. The FDA granted atezolizumab a priority review for this new indication.
Atezolizumab was previously approved for multiple indications, including several types, each, of NSCLC, small-cell lung cancer, urothelial cancer, and triple-negative breast cancer, for use as monotherapy or in combination with other agents.
On the same day, the FDA approved the VENTANA PD-L1 Assay as a companion diagnostic test for identifying appropriate patients with NSCLC and high PD-L1 expression as candidates for first-line treatment with atezolizumab for this indication.
“We are pleased to offer people with certain types of lung cancer a new chemotherapy-free option that can help prolong their lives,” said Levi Garraway, MD, PhD, Chief Medical Officer and Head of Global Product Development at Genentech. “Today marks the fifth approval of Tecentriq in lung cancer, as we remain committed to providing an effective and tailored treatment option for every person diagnosed with this disease.”
The efficacy of atezolizumab for this new indication was evaluated in the IMpower110 study, a multicenter, international, randomized, open-label clinical trial. IMpower110 included patients with stage IV NSCLC whose tumors express PD-L1 (TC ≥1% or IC ≥1%), who had not received chemotherapy for metastatic disease. Patients were randomized in a 1:1 ratio to intravenous atezolizumab 1200 mg every 3 weeks until disease progression or unacceptable toxicity. The main efficacy outcome measure was overall survival (OS).
The OS was significantly greater in patients with high PD-L1 tumor expression who received atezolizumab versus platinum-based chemotherapy, with a median OS of 20.2 months (95% confidence interval [CI], 16.5-not estimable) versus 13.1 months (95% CI, 7.4-16.5), respectively (hazard ratio [HR], 0.59; 95% CI, 0.40-0.89; P = .0106). At the interim or final analyses, the OS was not significantly different in the other 2 PD-L1 subgroups (TC ≥5% or IC ≥5%, and TC ≥1% or IC ≥1%).
The investigator’s assessed median progression-free survival (PFS) was 8.1 months (95% CI, 6.8-11.0) with atezolizumab versus 5 months (95% CI, 4.2-5.7) with platinum-based chemotherapy (HR, 0.63; 95% CI, 0.45-0.88). The overall response rate (ORR) per the investigator was 38% (95% CI, 29-48) and 29% (95% CI, 20-39), respectively.
The most common adverse events (≥20%) with atezolizumab as a single-agent therapy in the IMpower110 study were fatigue or asthenia.
The recommended atezolizumab dose for the treatment of NSCLC is 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks, administered intravenously over 60 minutes.