A Phase 3, Randomized study of atezolizumab plus bevacizumab and chemotherapy in patients with EGFR or ALK mutated in non-small cell lung cancer (ATTLAS, KCSG-LU19-04)

In the treatment of non-small cell lung cancer (NSCLC) with a driver mutation, the role of anti-PD-(L)1 antibody following tyrosine kinase inhibitor (TKI) remains unclear. This randomized, open-label, multicenter, phase 3 study evaluates the efficacy of atezolizumab plus bevacizumab, paclitaxel and carboplatin (ABCP) in EGFR or ALK-mutated NSCLC that progressed prior to TKI therapy.We compared the clinical efficacy of ABCP followed by maintenance therapy with atezolizumab plus bevacizumab with pemetrexed plus carboplatin or cisplatin (PC arm) followed by pemetrexed maintenance. The primary endpoint was progression-free survival (PFS).A total of 228 patients with activating EGFR mutation (n=215) or ALK translocation (n=13) were enrolled from 16 sites in the Republic of Korea and randomized at 2:1 ratio to either ABCP (n=154) or PC arm (n=74). The median follow-up duration was 26.1 months (95%CI 24.7-28.2). Objective response rates (69.5% vs 41.9%, P <0.001) and median PFS (8.48 vs. 5.62 months, hazard ratio [HR] 0.62 [0.45-0.86], P=0.004) were significantly better in the ABCP than PC arm. PFS benefit increased as PD-L1 expression increased, with HR of 0.47, 0.41, and 0.24 for PD-L1 ≥1%, ≥10% and ≥50%, respectively. Overall survival was similar between ABCP and PC arm (20.63 vs. 20.27 months, HR 1.01 [0.69-1.46], P=0.975). The safety profile of the ABCP arm was comparable to that previously reported, with no additional safety signals, but higher rates of treatment-related adverse events were observed compared to the PC arm.This study is the first randomized phase 3 study to demonstrate the clinical benefit of anti-PD-L1 antibody in combination with bevacizumab and chemotherapy in EGFR or ALK mutated NSCLC who have progressed on relevant targeted therapy.