Real-world survival outcomes and adverse events with adjuvant osimertinib in resected EGFR mutation-positive non-small cell lung cancer.

Abstract

e20003 Background: Adjuvant osimertinib (AO) significantly improved disease-free survival and overall survival among patients with resected stage IB to IIIA epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) in the phase 3 ADAURA trial. A 3-year duration of AO is now guideline recommended. Our study aimed to assess province-wide real-world outcomes of AO for patients with NSCLC harbouring canonical sensitizing EGFR mutations. Methods: A retrospective review was conducted using the Glans-Look Lung Cancer Research database, which captures patient-level demographic, clinical, and outcome data across Alberta, Canada. Patients had resected clinical stage IA-IIIA EGFR exon 19 deletion or L858R mutation and received AO in Alberta between September 2021 - November 2024. EGFR mutation status was obtained using the Agena iPLEX HS Lung panel or Oncomine Focus Assay. Disease-free survival was reported using summary statistics. Date of last follow-up was November 2024. Results: Of the 732 patients with EGFR positive NSCLC diagnosed between 2021 – 2024 in Alberta, 106 patients (14%) had early stage disease (defined as up to IIIA). A total of 25 patients received AO following resection of their NSCLC, with 24 patients (96%) having R0 resections. 11 patients (44%) received adjuvant chemotherapy prior to AO. Median follow up was 12.8 months from initiation of AO. Median duration of AO was 9.8 months (95% CI 6.7 to 16.7 months), with an average dose intensity of 92%. One patient (4%) had disease recurrence following AO, albeit this patient only received 12 days of AO due to toxicity. Disease-free survival ranged from 3.9 – 34.2 months. At the time of analysis, 24 patients (96%) were alive, with one death. Of the 29 adverse events (AE) recorded, there were 13 (45%) grade 1, 13 (45%) grade 2, 1 (3%) grade 4, and 2 (7%) AE of unknown grade. In ADAURA, of the 718 AE reported, there were 493 (69%) grade 1, 202 (28%) grade 2, and 22 (3%) grade 3 AE. Management of adverse events compared to ADAURA is outlined in Table 1. Median time to discontinuation of AO was 2.7 months. Conclusions: AEs occurred less frequently compared to ADAURA, although discontinuation of AO due to AE was higher in our experience, 28% vs. 11%, implying a poorer tolerability of AO in routine practice compared to the trial setting. Similar to ADAURA, most AE were low grade, suggesting that there may be an unmet need for more proactive symptom control to mitigate AE that may lead to discontinuation. Future studies require longer follow-up periods to better describe time to event endpoints for AO in this population. Management of adverse events in the current study compared to the ADAURA clinical trial. Management of Adverse Event Study Patients (n=25) ADAURA Patients (n=337) Dose Modification 4 (16%) 29 (9%) Treatment Break 5 (20%) 80 (24%) Hospitalization or Emergency Room Visit 2 (8%) N/A Discontinued 7 (28%) 37 (11%)