As reported in the Journal of Clinical Oncology by Roy S. Herbst, MD, PhD, of Yale Cancer Center and Yale School of Medicine, and colleagues, updated findings in the phase III ADAURA trial showed continued disease-free survival benefit with adjuvant osimertinib vs placebo after complete resection in EGFR-mutated stage IB to IIIA non–small cell lung cancer (NSCLC).
Roy S. Herbst, MD, PhD
The primary analysis of the trial supported the December 2020 approval of osimertinib in this setting. The disease-free survival hazard ratio (HR) in favor of osimertinib was 0.20 (99.12% confidence interval [CI] = 0.14–0.30, P < .001) in stage IB to IIIA disease.
Study Details
In the trial, 682 patients were randomly assigned between November 2015 and February 2019 to receive osimertinib 80 mg (n = 339) or placebo (n = 343) once daily for up to 3 years. If required on the basis of physician and patient choice, adjuvant chemotherapy was given prior to random assignment. The primary endpoint was investigator-assessed disease-free survival stage II to IIIA disease. Disease-free survival in the total population (stage IB–IIIA disease) was a secondary -endpoint.
Key Findings
In the updated exploratory analysis of final disease-free survival, median follow-up at data cutoff (in April 2022) was 44.2 months among 233 patients in the osimertinib group and 19.6 months among 237 patients in the placebo group in the stage II to IIIA population. Median disease-free survival was 65.8 months (95% CI = 54.4 months to not calculable) in the osimertinib group vs 21.9 months (95% CI = 16.6–27.5 months) in the placebo group (HR = 0.23, 95% CI = 0.18–0.30); 4-year rates were 70% vs 29%.
In the overall population with stage IB to IIIA disease, median disease-free survival was 65.8 months (95% CI = 61.7 months to not calculable) in the osimertinib group vs 28.1 months (95% CI = 22.1–35.0 months) in the placebo group (HR = 0.27, 95% CI = 0.21–0.34); 4-year rates were 73% vs 38%.
In the overall population, the osimertinib group had a lower rate of disease recurrence (27% vs 60%). Distant metastasis only was found in 13% vs 31% of patients, local/regional recurrence only in 12% vs 23%, and both in 2% vs 6%.
In the stage II–IIIA population, 4-year rates of central nervous system (CNS) disease-free survival were 90% vs 75% (HR = 0.24, 95% CI = 0.14–0.42). In the total population, 4-year rates were 92% vs 81% (HR = 0.36, 95% CI = 0.23–0.57).
The investigators reported that the long-term safety profile of osimertinib was consistent with the safety profile seen at the time of the primary analysis.
Conclusion
The investigators concluded: “These updated data demonstrate prolonged [disease-free survival] benefit over placebo, reduced risk of local and distant recurrence, improved CNS [disease-free survival], and a consistent safety profile, supporting the efficacy of adjuvant osimertinib in resected EGFR-mutated NSCLC.”
DISCLOSURE: The study was supported by AstraZeneca, the manufacturer of osimertinib. Dr. Herbst has served as a consultant or advisor for AstraZeneca, Bolt Biotherapeutics, Candel Therapeutics, Checkpoint Therapeutics, Cybrexa Therapeutics, EMD Serono, I-Mab Biopharma, Immune-Onc Therapeutics, Immunocore, Ocean Biomedical, Revelar Biotherapeutics, Ribbon Therapeutics, Xencor, Bristol Myers Squibb, DynamiCure Biotechnology, eFFECTOR Therapeutics, Eli Lilly and Company, Genentech, Gilead, HiberCell, Janssen, Johnson and Johnson, Loxo Oncology, Mirati Therapeutics NextCure, Novartis, Oncocyte Corp, Oncternal Therapeutics, Pfizer, Regeneron Pharmaceuticals, Roche, and Sanofi; has received research support from AstraZeneca, Eli Lilly and Company, Genentech/Roche, and Merck and Company; is on the Board of Directors for Immunocore and Junshi Pharmaceuticals; and has a leadership role with the American Association for Cancer Research, International Association for the Study of Lung Cancer, Society for Immunotherapy of Cancer, and Southwest Oncology Group.
Herbst R et al: J Clin Oncol. January 31, 2023 (early release online).
