196MO Anlotinib plus etoposide/carboplatin (EC) versus placebo plus EC in first-line therapy for extensive-stage small cell lung cancer (ES-SCLC): A randomized, double-blind, parallel controlled, phase III trial (ETER 701)

The overall survival (OS) improvement of immunochemotherapy in ES-SCLC is far from satisfactory. It is found that anlotinib (an anti-angiogenesis drug) could reprogram immunosuppressive tumor microenvironment and synergistic therapeutic benefits when combined with Immune checkpoint inhibitors and/or chemotherapy. ETER701 is the first randomized phase III trial evaluating anlotinib + etoposide/carboplatin (EC) ± benmelstobart (a novel developed PD-L1 inhibitor) vs placebo + EC in first-line ES-SCLC therapy. A historically longest OS was observed with anlotinib + EC + benmelstobart vs placebo + EC. Here we present the data of anlotinib + EC (anlotinib arm) vs placebo + EC (EC arm). In this multicentre, double-blind, placebo-controlled phase III study, eligible ES-SCLC patients were randomized (1:1:1) to receive benmelstobart + anlotinib + EC or placebo + anlotinib or placebo + EC for four 21-day cycles, followed by maintenance therapy with benmelstobart + anlotinib or placebo + anlotinib or placebo + EC. Co-primary endpoints were progression-free survival (PFS) assessed by the independent review committee (IRC) and OS in the intention-to-treat population. 738 patients were enrolled between March 18, 2020 and December 18, 2021. 245 patients were assigned to anlotinib arm and 247 to EC arm. With a median follow-up of 14.0 months (data cut-off May 14, 2022), median PFS in anlotinib arm was significantly longer than in EC arm (5.6 months vs 4.2 months; HR, 0.44; 95%CI, 0.36 to 0.55; P<0.0001), median OS was 13.3 months in anlotinib arm and 11.9 months in EC arm (HR, 0.86; 95%CI, 0.67-11.10; P=0.1723). The incidence of grade 3 or higher treatment-related adverse events was 94.3% vs 87.0%, and 2.5% vs 1.6% were grade 5, respectively. Anlotinib plus chemotherapy showed a significant PFS improvement and a numerical OS benefit over chemotherapy in the first-line ES-SCLC therapy. The survival benefits of anti-angiogenesis plus chemotherapy is comparable to immunochemotherapy, and the safety profile is tolerable and manageable.