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)

Background

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).

Methods

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.

Results

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.

Conclusions

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.

Clinical trial identification

NCT04234607.

Legal entity responsible for the study

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Funding

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.