Efficacy and safety of second-line treatments in patients with advanced EGFR-mutated non-small cell lung cancer progressing on osimertinib without identified targetable resistance mechanism at progression.

[INTRODUCTION] Osimertinib is a 3rd generation EGFR tyrosine kinase inhibitor, given in 1st line of treatment in advanced EGFR-mutated non-small cell lung cancer (NSCLC). Platinum-doublet chemotherapy for relapsed patients was recommended in 2nd line treatment, until recently. The aim of this retrospective observational multicentric French study was to describe the efficacy of the 2nd line treatments given after progression on osimertinib, before the implementation of the new standard of care based on the results of the Mariposa 2 trial.

[METHODS] We included all consecutive patients with advanced EGFR-mutated NSCLC treated with osimertinib in 1st line, between March 2018 and March 2023. Then we described the efficacy of the 2nd line treatments received by patients in whom no targetable mechanism of resistance was identified at progression. Best overall response rate (ORR), real-world progression-free survival (rwPFS) and overall survival (OS) were collected.

[RESULTS] Seventy-two patients were included. Among them, 38 received chemotherapy (CT) alone, 18, chemotherapy + bevacizumab (CB), 6, chemotherapy + osimertinib (CO), 4, chemotherapy + immunotherapy (CI), 4, chemotherapy + immunotherapy + bevacizumab (CIB) and 2, immunotherapy alone (IT). ORRs were CT=42%, CB=55. Median rwPFS were 5.8 months (95% CI 4.2-7.4) and 6.9 months (95% CI 4.5-9.2) for CT and CB respectively, and median OS 13.6 months (95% CI 11.1 - 16.1) and 15.0months (95% CI 11.1-18.9), for CT and CB respectively.

[CONCLUSION] 2nd line therapies received beyond osimertinib monotherapy in metastatic EGFR-mutated patients were mostly CT and CT + Bevacizumab. Recent studies have evaluated new molecules targeting the EGFR protein, offering new prospects for this group of patients.