LBA67 A phase III, 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 ofnon-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 and chemotherapy in EGFR or ALK-mutated NSCLC that progressed prior to TKI therapy. We compared the clinical efficacy of atezolizumab plus bevacizumab/paclitaxel/carboplatin (ABCP arm) 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 of 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 were higher in the ABCP arm than in the PC arm (69.5% vs 41.9%, P <0.001). Median PFS was significantly longer in the ABCP than in the PC arm (8.48 months vs. 5.62 months, hazard ratio [HR] 0.62 [0.45-0.86], P=0.004). 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 (20.63 months 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. 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.