FDA Approval Summary: Atezolizumab as Adjuvant Treatment following Surgical Resection and Platinum-Based Chemotherapy for Stage II to IIIA NSCLC

Luckson N. Mathieu, Erin Larkins, Arup K. Sinha, Pallavi S. Mishra-Kalyani, Samina Jafri, Shyam Kalavar, Soma Ghosh, Kirsten B. Goldberg, Richard Pazdur, Julia A. Beaver, Harpreet Singh

On October 15, 2021, the U.S. Food and Drug Administration (FDA) approved atezolizumab as adjuvant therapy in patients with stage II to IIIA non-small cell lung cancer (NSCLC) whose tumors have programmed death-ligand 1 (PD-L1) expression on ≥ 1% of tumor cells (TC), as detected by an FDA-approved test. The approval was based on results from the IMpower010 trial, in which 1005 patients with NSCLC who had completed tumor resection and cisplatin-based adjuvant chemotherapy were randomized 1:1 to receive atezolizumab for 16 cycles or best supportive care (BSC). The primary endpoint of disease-free survival (DFS) as assessed by investigator was tested hierarchically in the following analysis populations: stage II-IIIA NSCLC with PD-L1 expression on ≥ 1% of tumor cells (PD-L1 ≥ 1% TC); all randomized patients with stage II-IIIA NSCLC; and the intent-to-treat (ITT) population comprising all randomized patients. At the pre-specified interim DFS analysis, IMpower010 demonstrated a statistically significant and clinically meaningful improvement in DFS in the stage II-IIIA PD-L1 ≥ 1% TC analysis population, with a hazard ratio (HR) of 0.66 (95% CI 0.50, 0.88; p=0.004) favoring the atezolizumab arm. The safety profile of atezolizumab was generally consistent with known toxicities of anti-PD-(L) antibodies. The VENTANA PD-L1 (SP263) Assay (Ventana Medical Systems, Inc.) was contemporaneously approved as a companion diagnostic device to select patients with NSCLC who are PD-L1 ≥ 1% TC for adjuvant treatment with atezolizumab. Atezolizumab is the first immune checkpoint inhibitor approved by FDA for the adjuvant treatment of NSCLC.