Chemotherapy for patients with EGFR-mutated NSCLC after progression on EGFR-TKI’s: Exploration of efficacy of unselected treatment in a multicenter cohort study

Objectives In patients with Epidermal Growth Factor Receptor (EGFR)-mutated non-small cell lung (NSCLC) chemotherapy remains standard of care after progression on EGFR-tyrosine kinase inhibitors (TKIs). With the development of anti-angiogenic agents and immune checkpoint inhibitors the landscape of systemic regimens has changed significantly. This cohort study aims to evaluate the efficacy of chemotherapy regimens after progression on EGFR-TKI in a European population. Material and Methods All consecutive patients treated with chemotherapy after progression on EGFR-TKI for EGFR-mutated NSCLC, were identified in two tertiary centers in the Netherlands. Data on best response, progression free survival (PFS) and overall survival (OS) were extracted from medical records. Results In total, 171 lines of chemotherapy were identified: platinum/pemetrexed (PP, n=95), carboplatin/paclitaxel/bevacizumab/atezolizumab (CPBA, n=32), paclitaxel/bevacizumab (PB, n=36) and carboplatin/paclitaxel/bevacizumab (CPB, n=8). Of the 171 lines, 106 were given as first-line after EGFR-TKI. Median PFS did not differ significantly between the first-line regimens (p=0.50), with the highest PFS in PP (5.2 months [95% CI 4.5-5.9]) and CPBA (5.9 months [95% CI 3.8-80]). The majority of the PB group (n=32) received this regimen in a second- or later line with a median PFS of 4.9 months (95% CI 3.3-6.6). First-line regimens had a median OS of 15.3 months (95% CI 11.6-18.9) with no significant difference between regimens (p=0.85). Conclusion After progression on EGFR-TKI, patients with EGFR-mutated NSCLC show substantial benefit on different chemotherapy regimens. In particular, favorable outcomes were seen in patients treated with PP and CPBA as first-line chemotherapy, and PB in further lines of chemotherapy.