Neoadjuvant Osimertinib for Resectable EGFR-Mutated Non–Small Cell Lung Cancer

Abstract

Neoadjuvant; Resectable; Non-small cell lung cancer

Neoadyuvante; Resecable; Cáncer de pulmón de células no pequeñas

Neoadjuvant; Resecable; Càncer de pulmó de cèl·lules no petites

Purpose: Adjuvant osimertinib is the standard of care for patients with resected epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Neoadjuvant treatment could improve surgical and long-term outcomes. Methods: In this randomized, controlled, phase III study, patients with resectable, EGFR-mutated, stage II-IIIB NSCLC were randomly assigned (1:1:1) to receive neoadjuvant osimertinib (80 mg orally once daily for ≥9 weeks) plus platinum-based chemotherapy (once every 3 weeks for three cycles), osimertinib monotherapy (for ≥9 weeks), or placebo plus platinum-based chemotherapy (control), followed by surgical resection. Adjuvant osimertinib was offered to eligible patients after completion of surgery. The primary end point was major pathologic response (MPR) by blinded central pathology review. Event-free survival (EFS) was a secondary end point. Results: Overall, 358 patients were randomly assigned to receive osimertinib plus chemotherapy (121 patients), osimertinib monotherapy (117 patients), or placebo plus chemotherapy (120 patients). Osimertinib plus chemotherapy (MPR rate 26%) and osimertinib monotherapy (25%) demonstrated statistically significant improvement in the MPR rate versus placebo plus chemotherapy (2%), with corresponding odds ratios of 19.82 (95.002% CI, 4.60 to 85.33; P < .0001) and 19.28 (99.9% CI, 1.71 to 217.39; P < .0001), respectively. With 15% data maturity, the EFS rates at 12 months were 93%, 95%, and 83% with osimertinib plus chemotherapy, osimertinib monotherapy, and placebo plus chemotherapy, respectively. In the neoadjuvant period, grade ≥3 adverse events of any cause occurred in 36%, 13%, and 33% of patients with osimertinib plus chemotherapy, osimertinib monotherapy, and placebo plus chemotherapy, respectively. No new safety concerns were identified. Conclusion: Neoadjuvant osimertinib with or without chemotherapy demonstrated statistically significant improvement in the MPR rate over chemotherapy alone in patients with resectable, EGFR-mutated, stage II-IIIB NSCLC. Trial registration: ClinicalTrials.gov NCT04351555.

J.E.C. acknowledges the support of the National Institutes of Health (NIH) through the P30 grant (NCI Cancer Center Support Grant P30 CA008784 PI Vickers). The authors acknowledge Aaron Korpal, PhD, of Ashfield MedComms, an Inizio company, for medical writing support that was funded by AstraZeneca in accordance with Good Publications Practice (GPP) guidelines (https://www.ismpp.org/gpp-2022). A complete list of the NeoADAURA trial investigators is provided in the Appendix (online only).