On October 15, 2021, the U.S. Food and Drug Administration (FDA) approved atezolizumab (Tecentriq®) for adjuvant treatment following resection and platinum-based chemotherapy in patients with stage II–IIIA non-small cell lung cancer (NSCLC) with PD-L1 expression on ≥ 1% of tumor cells as determined by an FDA-approved test.
FDA also approved the VENTANA PD-L1 (SP263) assay as a companion diagnostic device to select patients with NSCLC for adjuvant treatment with atezolizumab.
Efficacy was demonstrated in a multi-center, randomized, open-label trial (Impower010; NCT02486718) in patients with stage IB (tumors ≥ 4 cm) through stage IIIA NSCLC (per the International Union Against Cancer/American Joint Committee on Cancer staging system, seventh edition). A total of 1,005 patients who had complete tumor resection and cisplatin-based adjuvant chemotherapy were randomized 1:1 to receive atezolizumab 1,200 mg every three weeks for 16 cycles or best supportive care (BSC).
The major efficacy outcome measure was disease-free survival (DFS) as assessed by the investigator in the primary efficacy analysis population (n = 476) of patients with stage II–IIIA NSCLC with PD-L1 expression on ≥ 1% of tumor cells (PD-L1 ≥ 1% TC). Median DFS was not reached (95% CI = 36.1, NE) in patients on the atezolizumab arm compared with 35.3 months (95% CI = 29.0, NE) on the BSC arm (HR = 0.66; 95% CI = 0.50, 0.88; p = 0.004).
In a prespecified secondary subgroup analysis of patients with PD-L1 TC ≥ 50% stage II–IIIA NSCLC, the DFS HR was 0.43 (95% CI = 0.27, 0.68). In an exploratory subgroup analysis of patients with PD-L1 TC 1-49% stage II–IIIA NSCLC, the DFS HR was 0.87; (95% CI = 0.60, 1.26).
The most common adverse reactions reported in 10% or more of patients receiving atezolizumab, including laboratory abnormalities, were increased aspartate aminotransferase, blood creatinine, or alanine aminotransferase; hyperkalemia; rash; cough; hypothyroidism; pyrexia, fatigue or asthenia; musculoskeletal pain; peripheral neuropathy; arthralgia; and pruritus.
The recommended atezolizumab dose for the indication is 840 mg every two weeks, 1,200 mg every three weeks, or 1,680 mg every four weeks for up to one year.
View the full prescribing information for atezolizumab.
The review was conducted under Project Orbis, an initiative of FDA’s Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For the review, FDA collaborated with the Australian Therapeutic Goods Administration, Brazilian Health Regulatory Agency, Health Canada, Switzerland’s Swissmedic, and United Kingdom’s Medicines and Healthcare Products Regulatory Agency. The application reviews are ongoing at other regulatory agencies.
The review used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. FDA approved the application six weeks ahead of FDA’s goal date.
FDA granted the application priority review. A description of FDA expedited programs is in the Guidance for IndustryꟷExpedited Programs for Serious ConditionsꟷDrugs and Biologics.
Healthcare professionals should report all serious adverse events they suspect are associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.