On October 15, 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 to IIIA non–small cell lung cancer (NSCLC) whose tumors have PD-L1 expression on ≥ 1% of tumor cells, as determined by an FDA-approved test.
The 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 the multicenter, randomized, open-label IMpower010 trial in patients with stage IB (tumors ≥ 4 cm) through stage IIIA NSCLC (per Union for International Cancer Control/American Joint Committee on Cancer staging system, 7th edition). A total of 1,005 patients who underwent complete tumor resection and received cisplatin-based adjuvant chemotherapy were randomly assigned 1:1 to receive atezolizumab at 1,200 mg every 3 weeks for 16 cycles or best supportive care.
The major efficacy outcome measure was disease-free survival as assessed by the investigator in the primary efficacy analysis population (n = 476) of patients with stage II to IIIA NSCLC with PD-L1 expression on ≥ 1% of tumor cells.
Median disease-free survival was not reached (95% confidence interval [CI] = 36.1 months–not evaluable) in patients treated with atezolizumab compared with 35.3 months (95% CI = 29.0–not evaluable) among those treated with best supportive care (hazard ratio = 0.66, 95% CI = 0.50–0.88, P = .004).
In a prespecified secondary subgroup analysis of patients with stage II to IIIA NSCLC and PD-L1 expression on ≥ 50% of tumor cells, the disease-free survival hazard ratio was 0.43 (95% CI = 0.27–0.68). In an exploratory subgroup analysis of patients with stage II to IIIA NSCLC and PD-L1 tumor cell expression of 1% to 49%, the disease-free survival hazard ratio was 0.87 (95% CI = 0.60–1.26).
The most common (≥ 10%) adverse reactions in patients receiving atezolizumab, including laboratory abnormalities, were increased aspartate aminotransferase, blood creatinine, and alanine aminotransferase; as well as hyperkalemia, rash, cough, hypothyroidism, pyrexia, fatigue/asthenia, musculoskeletal pain, peripheral neuropathy, arthralgia, and pruritus.
The recommended atezolizumab dose for this indication is 840 mg every 2 weeks, 1,200 mg every 3 weeks, or 1,680 mg every 4 weeks for up to 1 year.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency, Health Canada, Switzerland’s Swissmedic, and the United Kingdom’s Medicines and Healthcare products Regulatory Agency. The application reviews are ongoing at the other regulatory agencies.
This 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 the FDA’s assessment. The FDA approved this application 6 weeks ahead of the FDA goal date. This application was also granted Priority Review.