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)

Background

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.

Methods

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).

Results

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.

Conclusions

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.

Clinical trial identification

NCT03991403.

Editorial acknowledgement

This study is under consideration of simultaneous publication in Journal of Clinical Oncology and it is pre-discussed with JCO editorial board.

Legal entity responsible for the study

Myung-Ju Ahn.

Funding

Roche.

Disclosure

All authors have declared no conflicts of interest.