On October 15, 2021, atezolizumab was approved for adjuvant treatment following resection and platinum-based chemotherapy in patients with stage II to IIIA non–small cell lung cancer (NSCLC) with PD-L1 expression on ≥ 1% of tumor cells, as determined by a U.S. Food and Drug Administration (FDA)-approved test.1,2
The FDA simultaneously approved the VENTANA PD-L1 (SP263) Assay as a companion diagnostic device to select patients for atezolizumab treatment.
Supporting Efficacy Data
Approval was based on findings in the primary efficacy population of the phase III double-blind IMpower010 study (ClinicalTrials.gov identifier NCT02486718). The population consisted of 476 patients with stage II to IIIA NSCLC with PD-L1 ≥ 1% who were randomly assigned to receive atezolizumab at 1,200 mg every 3 weeks for 16 cycles (n = 248) or best supportive care (n = 228) after resection and cisplatin-based adjuvant chemotherapy.
Atezolizumab has warnings/precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryofetal toxicity.
Investigator-assessed median disease-free survival was not reached (95% confidence interval [CI] = 36.1 months to not estimable) in the atezolizumab group vs 35.3 months (95% CI = 29.0 months to not estimable) in the best supportive care group (hazard ratio = 0.66, 95% CI = 0.50–0.88, P = .004). In subgroup analyses, hazard ratios were 0.43 (95% CI = 0.27–0.68) among patients with PD-L1 ≥ 50% and 0.87 (95% CI = 0.60–1.26) among those with PD-L1 of 1% to 49%.
How It Is Used
The recommended atezolizumab dose for the current 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.
No dose reductions are recommended. Prescribing information provides instructions on dosage modifications for immune-mediated adverse reactions and infusion-related reactions.
Among the total of 495 patients receiving atezolizumab in the IMpower010 trial, the most common adverse events of any grade were rash (17%), cough (16%), hypothyroidism (14%), pyrexia (14%), fatigue/asthenia (14%), musculoskeletal pain (14%), and peripheral neuropathy (12%). The most common grade 3 or 4 adverse events included rash (1.2%), pyrexia (0.8%), and musculoskeletal pain (0.8%). The most common grade 3 or 4 laboratory abnormalities were hyperkalemia (3.5%) and increased alanine aminotransferase (ALT, 3.3%) and aspartate aminotransferase (AST, 2.5%)
Serious adverse events occurred in 18% of patients, most commonly pneumonia (1.8%), pneumonitis (1.6%), and pyrexia (1.2%). Adverse events led to treatment discontinuation in 18% of patients, most commonly due to pneumonitis (2.2%), hypothyroidism (1.6%), increased AST (1.4%), arthralgia (1.0%), and increased ALT (1.0%). Adverse events led to death in 1.8%, due to multiple organ dysfunction syndrome, pneumothorax, interstitial lung disease, arrhythmia, acute cardiac failure, myocarditis, cerebrovascular accident, death of an unknown cause, and acute myeloid leukemia in one patient each.
Atezolizumab has warnings/precautions for immune-mediated adverse reactions (including pneumonitis, colitis, hepatitis, endocrinopathies, dermatologic reactions, nephritis and renal dysfunction, and solid organ transplant rejection), infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving atezolizumab.
1. U.S. Food and Drug Administration: FDA approves atezolizumab as adjuvant treatment for non-small cell lung cancer. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-atezolizumab-adjuvant-treatment-non-small-cell-lung-cancer. Accessed Novemer 16, 2021.
2. Tecentriq (atezolizumab) injection prescribing information, Genentech, Inc, October 2021. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761034s042lbl.pdf. Accessed November 8, 2021.