Neoadjuvant and adjuvant osimertinib in stage IA-IIIA, EGFR-mutant non-small cell lung cancer (NORA)

Abstract

Introduction: Treatment with adjuvant osimertinib for three years is the standard-of-care for resected stage IB-IIIA non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)-mutations. The role of neoadjuvant osimertinib in the perioperative setting is yet to be elucidated in the NeoADAURA study (NCT04351555).

Methods: This is a single center, pilot study of patients with clinical stage IA-IIIA NSCLC (AJCC 8th edition) harboring an activating EGFR mutation (Exon 19 deletion, L858R) (NCT04816838). Patients were treated with two 28-day cycles of neoadjuvant osimertinib followed by surgical resection and 3 years of adjuvant osimertinib. The primary endpoint was objective response rate (ORR) after 2 cycles of neoadjuvant treatment. Secondary endpoints included pathologic complete response (pCR) rate and major pathologic response (MPR) rate. Exploratory objectives included the correlation of longitudinal circulating tumor DNA (ctDNA) testing (Signatera) and response to neoadjuvant osimertinib.

Results: A total of 25 patients were enrolled and treated with neoadjuvant osimertinib, and all patients received surgical resection with R0 resection. The ORR was 44% (n=11) all of which were partial responses. Fourteen patients (56%) showed stable disease (SD) following neoadjuvant osimertinib. MPR and PCR rates were 24% (n=6) and 0%, respectively. None of the patients received adjuvant chemotherapy. The median disease free survival (DFS) was not reached at a median follow-up of 31 months (range, 13.8-38.6 months). Six patients (30%) were ctDNA-positive at baseline and achieved clearance after 1 cycle of neoadjuvant osimertinib. There were no grade 3 adverse events (AEs) during neoadjuvant treatment.

Conclusions: Two cycles of neoadjuvant osimertinib did not meet its primary endpoint of ORR. Neoadjuvant osimertinib is a feasible approach with a manageable safety profile in resectable EGFR-mutant NSCLC.