Osimertinib shows promise as an adjuvant treatment for patients with stage IB to IIIA EGFR mutation–positive NSCLC.
Osimertinib, a third-generation central nervous system (CNS)-active EGFR-targeting tyrosine kinase inhibitor, is approved for the first-line treatment of patients with metastatic non–small-cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletions or exon 21L858R mutations as detected by a US Food and Drug Administration–approved test.1,2
The double-blind, randomized phase 3 ADAURA trial evaluated the efficacy and safety of osimertinib compared with placebo in patients with completely resected, stage IB to IIIA, EGFR mutation–positive NSCLC, after adjuvant chemotherapy.1 Following independent data monitoring committee recommendations, the trial was unblinded early due to efficacy. The researchers reported interim results from the trial, which included 682 patients who were randomized to osimertinib 80 mg once daily (N = 339) or placebo (N = 343) for 3 years. The primary end point was investigator-assessed disease-free survival (DFS) among patients with stage II to IIIA disease (N = 470). Secondary end points included DFS in the overall population of patients with stage IB to IIIA disease, overall survival (OS), and safety.1
At 24 months in patients with stage II to IIIA disease, 90% (95% confidence interval [CI], 84%-93%) of those in the osimertinib group and 44% (95% CI, 37%-51%) of those in the placebo group were alive and disease-free (hazard ratio [HR], 0.17; P <.001).1 Median DFS was not reached (95% CI, 38.8 months-not calculable [NC]) in the osimertinib group compared with 19.6 months (95% CI, 16.6-24.5 months) in the placebo group. At 24 months in the overall population, 89% (95% CI, 85%-92%) of those in the osimertinib group and 52% (95% CI, 46%-58%) of those in the placebo group were alive and disease-free at 24 months (HR, 0.20; P <.001). Median DFS was not reached (95% CI, NC-NC) in the osimertinib group compared with 27.5 months (95% CI, 22.0-35.0 months) in the placebo group. A clinically meaningful increase in CNS DFS was observed in the osimertinib group versus the placebo group (98% [95% CI, 95-99] vs 85% [95% CI, 80-89]; HR, 0.18; 95% CI, 0.10-0.33). OS data were immature. At the data cutoff, 9 deaths occurred in the osimertinib group and 20 in the placebo group.1
The most common adverse events (AEs) of any grade with osimertinib were diarrhea (46% vs 20% in the placebo group), paronychia (25% vs 1%), and dry skin (23% vs 6%).1 Grade ≥3 AEs occurred in 20% of patients in the osimertinib group and 13% of those in the placebo group. Serious AEs were reported in 16% of patients in the osimertinib group compared with 12% of those in the placebo group. AEs led to treatment discontinuation in 11% of patients in the osimertinib group and 3% of those in the placebo group. No fatal AEs were reported with osimertinib; 1 fatal AE (pulmonary embolism) occurred with placebo.1
The researchers concluded that osimertinib is an effective new treatment in the adjuvant setting for patients with stage IB to IIIA EGFR mutation–positive NSCLC.1
1. Wu YL, et al. N Engl J Med. 2020;383:1711-1723.
2. US Food and Drug Administration. FDA approves osimertinib for first-line treatment of metastatic NSCLC with most common EGFR mutations. www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-osimertinib-first-line-treatment-metastatic-nsclc-most-common-egfr-mutations. Accessed December 17, 2020.