A randomised non-comparative phase II study of atezolizumab, bevacizumab and chemotherapy in EGFR-mutant NSCLC with acquired resistance - The ETOP 15-19 ABC-lung trial

Science and Research

BACKGROUND: ABC-lung explores the potential effect of combining atezolizumab and bevacizumab with either carboplatin/paclitaxel (ABCPac) or pemetrexed (ABPem) in patients with EGFR-mutant NSCLC, resistant to tyrosine kinase inhibitors (TKIs). METHODS: ABC-lung is a 1:1 randomised, non-comparative, phase II trial, stratified by prior treatment with a third-generation EGFR TKI, evaluating atezolizumab (1200 mg, Q3W) and bevacizumab (15mg/kg, Q3W) with either 4-6 cycles of carboplatin (AUC5, Q3W) and paclitaxel (175-200mg/m2, Q3W) or pemetrexed (500 mg/m2, Q3W) until progression (PD). The study aimed to improve the 1-year progression-free survival (PFS) rate from 18% to 37%, assessed per RECISTv1.1, separately in each arm. To reject the null hypothesis, at least 14 of 45 evaluable patients in each arm needed to be progression-free at 1-year (power 83%, 1-sided a=0.023). Secondary endpoints included overall survival (OS), objective response rate (ORR), PFS, quality of life (QoL) and adverse events (AEs). RESULTS: Between 09/2020 and 09/2022, 95 patients were randomized (ABCPac:45; ABPem:50) with median follow-up time of 19 months. From the evaluable patients, 9 in ABCPac and 11 in ABPem arms reached 1-year without progression, lower than the success criterion of 14patients. Median PFS was 6.4 months in ABCPac and 7.6 months in the ABPem arms, while median OS was 15.4 months and 15.6 months, respectively. Grade