Atezolizumab Plus Bevacizumab and Chemotherapy Fails to Improve Survival for EGFR-Mutated Non-Small Cell Lung Cancer

According to results from the phase 3 ETOP 15-19 ABC-lung trial, atezolizumab plus bevacizumab and chemotherapy failed to improve survival outcomes for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) that is resistant to tyrosine kinase inhibitors (TKIs). 

“One of the preferred standard first-line treatments for patients…is a third-generation EGFR TKI such as osimertinib monotherapy…however, despite a high response rate and prolonged progression-free survival (PFS), acquired resistance and disease progression are inevitable,” stated Ross Soo, MD, National University Cancer Institute, Singapore, Singapore, and coauthors. “In this study, we aim to confirm the efficacy of atezolizumab, bevacizumab, carboplatin-paclitaxel and also to explore the efficacy of an investigational backbone of atezolizumab, bevacizumab and pemetrexed.” 

In this non-comparative study, 95 patients were randomized on a 1-to-1 basis to receive 1200 mg of atezolizumab plus 15 mg/kg of bevacizumab with either 4-to-6 cycles of carboplatin (AUC5) and 175 to 200 mg/m² of paclitaxel (ABCPac; n = 45), or 500 mg/m² pemetrexed (ABCPem; n = 50), every 3 weeks until disease progression. Patients were stratified based on prior treatment with a third-generation TKI. The primary end point was the number of patients progression-free at 1 year. Secondary end points included PFS, overall survival (OS), objective response rate (ORR), and safety. 

At a median follow-up of 19 months, 9 patients reached 1-year without progression in the ABCPac arm and 11 patients reached 1-year without progression in the ABCPem arm, which was lower than the threshold of 14 patients. Median PFS was 6.4 months in the ABCPac arm and 7.6 months in the ABCPem arm. Median OS was 15.4 months and 15.6 months, respectively. Grade ≥3 treatment-related adverse events occurred in 50% of patients in the pembrolizumab arm and 42% of patients in the pemetrexed arm. No grade 5 adverse events were reported. 

“Treatment with either ABCPac or ABPem in patients with advanced NSCLC harbouring common sensitising EGFR mutations and acquired resistance to EGFR TKIs did not improve the 12-month PFS rates,” concluded Dr Soo et al. “Therapeutic strategies beyond an ICI-based approach are being pursued and are indeed a major area of great clinical trial activity at present.”

Source:

Soo RA, Vervita K, Fruh M, et al. 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. Clin Lung Cancer. Published online: February 20, 2025. doi: 10.1016/j.lungcan.2025.108454