As reported in The New England Journal of Medicine by Masahiro Tsuboi, MD, and colleagues, the planned final overall survival analysis of the phase III ADAURA trial has shown a significant benefit with osimertinib vs placebo in patients with resected EGFR-mutant non–small cell lung cancer (NSCLC). The trial supported the December 2020 approval of osimertinib in this setting on the basis of improved disease-free survival, the study’s primary endpoint.
Masahiro Tsuboi, MD
Study Details
In the international double-blind trial, 682 patients with stage IB to IIIA disease and EGFR exon 19 deletions or exon 21 L858R mutations, who did or did not receive prior adjuvant chemotherapy, were randomly assigned between November 2015 and February 2019 to receive osimertinib at 80 mg once daily (n = 339) or placebo (n = 343) until disease recurrence, completion of the trial regimen at 3 years, or meeting of discontinuation criteria.
Key Findings
Among 233 patients in the osimertinib group vs 237 in the placebo group with stage II to IIIA disease, median follow-up was 59.9 months (range = 0–82 months) and 56.2 months (range = 1–86 months). Overall survival at 5 years was 85% (95% confidence interval [CI] = 79%–89%) in the osimertinib group vs 73% (95% CI = 66%–78%) in the placebo group (hazard ratio [HR] = 0.49, 95.03% CI = 0.33–0.73, P < .001).
Among all patients (stage IB–IIIA disease), median follow-up was 60.4 months (range = 0–82 months) in the osimertinib group and 59.4 months (range = 1–86 months) in the placebo group. Overall survival at 5 years was 88% (95% CI = 83%–91%) in the osimertinib group vs 78% (95% CI = 73%–82%) in the placebo group (HR = 0.49, 95.03% CI = 0.34–0.70, P < .001).
Subsequent anticancer treatments were received by 76 patients in the osimertinib group (22%) and 184 patients in the placebo group (54%). The most commonly received were EGFR tyrosine kinase inhibitors.
The safety profile of osimertinib was consistent with that at the primary analysis of disease-free survival.
The investigators concluded, “Adjuvant osimertinib provided a significant overall survival benefit among patients with completely resected, EGFR-mutated, stage IB to IIIA NSCLC.”
Masahiro Tsuboi, MD, of National Cancer Center Hospital East, Kashiwa, Japan; Roy S. Herbst, MD, PhD, of Yale School of Medicine and Yale Cancer Center; and Yi‑Long Wu, MD, of Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangzhou, China, are the corresponding authors for The New England Journal of Medicine article.
Disclosure: The study was funded by AstraZeneca. For full disclosures of the study authors, visit nejm.org.
