Osimertinib Extends Disease-Free Survival in Resected EGFR-Mutated NSCLC in Phase 3 ADAURA Trial

Interim analysis results from the double-blind, phase 3 ADAURA trial demonstrated that among patients with stage IB to IIIA EGFR-positive non-small cell lung cancer (NSCLC), disease-free survival was significantly longer among those who received osimertinib (Tagrisso) than among those who received placebo.

The study, published in The New England Journal of Medicine, suggests that osimertinib as adjuvant therapy is an effective treatment strategy for this patient population following complete tumor resection.

“The use of adjuvant chemotherapy according to disease stage before randomization in the ADAURA trial was consistent with the uptake reported in clinical trials and with practice in the community observed in real-world studies across different regions,” the authors wrote.

In the study, researchers randomly assigned patients with completely resected EGFR mutation-positive NSCLC 1:1 to receive either 80 mg of osimertinib once daily or placebo for 3 years. The primary end point was disease-free survival among patients with stage II to IIIA disease, per investigator assessment, and key secondary end points included disease-free survival in the overall population of patients with stage IB to IIIA disease, overall survival (OS), and safety.

In total, 682 patients were randomized, including 339 to the osimertinib group and 343 to the placebo group.

After 2 years, 90% of the patients with stage II to IIIA disease in the osimertinib group (95% CI, 84-93) and 44% of those in the placebo group (95% CI, 37-51) were alive and disease-free (HR, 0.17; 99.06% CI, 0.11-0.26; P < .001). In the overall population of patients, 89% of those in the osimertinib group (95% CI, 85-92) and 52% of those in the placebo group (95% CI, 46-58) were alive and disease-free at 2 years (HR, 0.20; 99.12% CI, 0.14-0.30; P < .001).

“The disease-free survival benefit with osimertinib was observed irrespective of whether patients received adjuvant chemotherapy or not,” added the authors.

Moreover, 98% of the patients in the osimertinib group (95% CI, 95-99) and 85% of those in the placebo group (95% CI, 80-89) were alive and did not have central nervous system disease after 24 months (HR, 0.18; 95% CI, 0.10-0.33).

OS data were immature at the time of analysis, though 29 patients had died, including 9 in the osimertinib group and 20 in the placebo group. The patients and investigators have continued to remain unaware of the trial-group assignments, and follow-up is ongoing.

Overall, 680 patients were included in the safety analysis, including 337 in the osimertinib group and 343 in the placebo group; no new safety signals were recorded. Adverse events (AEs) were reported in 329 patients (98%) in the osimertinib group and in 306 patients (89%) in the placebo group.

AEs of grade 3 or higher were reported in 68 patients (20%) in the osimertinib group and in 46 patients (13%) in the placebo group. Serious AEs were reported in 54 patients (16%) in the osimertinib group and in 42 patients (12%) in the placebo group.No fatal adverse events were reported in the osimertinib group and only 1 event (a pulmonary embolism) occurred in the placebo group.

“Future considerations for the ADAURA trial include subsequent treatment, longitudinal assessment of minimal residual disease, and acquired resistance mechanisms at relapse,” the authors noted.

The NeoADAURA (NCT04351555) and LAURA (NCT03521154) trials are also currently under way to investigate the efficacy and safety of neoadjuvant osimertinib in patients with EGFR-positive resectable NSCLC and osimertinib after chemoradiation in stage III unresectable EGFR-positive NSCLC, respectively.

Reference:

Wu Y, Tsuboi M, He J, et al. Osimertinib in Resected EGFR-Mutated Non–Small-Cell Lung Cancer. The New England Journal of Medicine. doi: 10.1056/NEJMoa2027071