1789P - Second OS interim analysis from BEAT-SC: A randomized phase III study of bevacizumab (bev) or placebo in combination with atezolizumab and platinum-based chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC)

Background

Atezolizumab combined with carboplatin and etoposide is approved as first-line treatment for patients with ES-SCLC, based on results from the Phase I/III IMpower133 trial (NCT02763579). The VEGF inhibitor bev is approved for the treatment of many tumor types and has synergistic effects when combined with atezolizumab, as demonstrated by the Phase III IMpower150 study (NCT02366143) in non-small cell lung cancer. BEAT-SC (jRCT2080224946) is evaluating the efficacy and safety of bev combined with atezolizumab and platinum-based chemotherapy in patients with ES-SCLC from Japan and China. The primary analysis of the study demonstrated superior progression-free survival (PFS) with addition of bev to atezolizumab + cisplatin or carboplatin + etoposide (ACE). First interim overall survival (OS) data were immature (Ohe et al., ASCO 2024). Here, we report the second OS interim analysis data.

Methods

Eligible patients had measurable ES-SCLC, were ≥20 y of age (≥18 y for patients in China), had an ECOG performance status of 0 or 1 and had no prior systemic treatment for ES-SCLC. Patients were randomized 1:1 to receive 4 cycles (21 days/cycle) of induction therapy with bev combined with ACE or placebo combined with ACE, followed by maintenance therapy with bev + atezolizumab or placebo + atezolizumab, respectively. The primary endpoint was investigator-assessed PFS (INV-PFS). Key secondary endpoints included OS and safety.

Results

At data cutoff (Jan 10, 2024; median follow-up, 12.42 mo), median INV-PFS was 5.7 mo for bev + ACE vs 4.4 mo for placebo + ACE (stratified HR, 0.73; 95% CI: 0.58, 0.93). Median OS was 13.9 mo for bev + ACE vs 16.4 mo for placebo + ACE (stratified HR, 1.13; 95% CI: 0.85, 1.49; P=0.3995; 2-sided α boundary=0.0191). No new safety signals were observed.

Conclusions

In this analysis, the addition of bev to ACE showed favorable PFS vs placebo + ACE, consistent with the primary analysis. OS data were still immature at the second interim OS analysis, and the numerical OS improvement of bev + ACE was not shown vs placebo + ACE. OS follow-up will continue.

Clinical trial identification

jRCT2080224946.

Editorial acknowledgement

Editorial assistance was provided by Lidija Garan, PhD, of Nucleus Global, an Inizio Company and funded by Chugai Pharmaceutical Co., Ltd.

Legal entity responsible for the study

Chugai Pharmaceutical Co., Ltd and F. Hoffmann-La Roche Ltd.

Funding

Chugai Pharmaceutical Co., Ltd, and F. Hoffmann-La Roche Ltd.

Disclosure

Y. Ohe: Financial Interests, Personal, Advisory Board: Amgen, AnHeart Therapeutics Inc, AstraZaneca, BMS, Celltrion, Nippon Kayaku, ONO, Pfizer, Takeda, PharmaMar, AnHeart; Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Eisai, Eli Lilly, MSD, Novartis, ONO, Takeda; Financial Interests, Institutional, Local PI: AstraZeneca, Janssen, Amgen; Financial Interests, Personal and Institutional, Coordinating PI: Takeda, ONO; Non-Financial Interests, Leadership Role: JSMO, JLCS, JCOG; Non-Financial Interests, Member: ASCO. M. Nishio: Financial Interests, Personal, Invited Speaker, lectures fee: Ono Pharmaceuticals; Financial Interests, Personal, Invited Speaker, lectures: Chugai Pharmaceutical, Taiho Pharmaceutical, Bristol Myers Squibb, Daiichi Sankyo, AstraZeneca, MSD, AbbVie, Takeda, Pfizer, Boehringer Ingelheim, Novartis, Nippon Kayaku, Merck, Janssen; Financial Interests, Personal, Invited Speaker, lectures,: Lilly. S. Watanabe: Financial Interests, Personal, Funding, Medical writing: Chugai Pharmaceutical; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Nippon Kayaku; Financial Interests, Personal, Other, Lecture Fee: Lilly, Chugai Pharmaceutical, Ono Pharmaceutical, Taiho Pharmaceutical, Kyowa Kirin, Takeda Pharmaceutical, AstraZeneca, Novartis Pharmaceutical, Bristol Myers Squibb, Daiichi Sankyo, Nippon Kayaku, Merck, Celltrion. S. Murakami: Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Chugai pharmaceutical, MSD, Ono pharmaceutical, Takeda Pharmaceutical, Eli Lilly Japan, Bristol Myers Squibb, Merck BioPharma, Daiichi Sankyo; Financial Interests, Institutional, Local PI: AstraZeneca, Chugai pharmaceutical, Daiichi Sankyo, Ono pharmaceutical, Janssen Pharmaceutical, MSD, Sanofi. I. Okamoto: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical, Boehringer Ingelheim, AstraZeneca, Bristol Myers Squibb, Takeda Pharmaceutical, Daiichi Sankyo, MSD, Pfizer, Taiho Pharmaceutical, Novartis; Financial Interests, Institutional, Local PI: Chugai Pharmaceutical, Boehringer Ingelheim, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, GSK, MSD, Taiho Pharmaceutical, Novartis. N. Katakami: Financial Interests, Personal, Invited Speaker: AstraZeneca, Takeda Pharmaceutical, Chugai Pharmaceutical, Kyorin Pharmaceutical, Bristol Myer Squibb Ono Pharmaceutical, Boehringer Ingelheim, Kyowa-Kirin, Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Local PI: Chugai Pharmaceutical. Y. Nakagawa: Financial Interests, Institutional, Full or part-time Employment: Chugai Pharmaceutical Co., Ltd.; Financial Interests, Institutional, Stocks/Shares: Chugai Pharmaceutical Co., Ltd. M. Hayashi: Financial Interests, Institutional, Full or part-time Employment: Chugai Pharmaceutical Co.,Ltd. T. Nanki: Financial Interests, Personal, Invited Speaker: GSK plc., Eisai Co., Ltd., AstraZeneca K.K., Chugai Pharmaceutical Co., Nippon Boehringer Ingelheim Co.,Ltd., Eli Lilly Japan K.K., Astellas Pharma Inc., Ono Pharmaceutical Co., Asahikasei Pharma Corp., AbbVie GK, Taiho Pharmaceutical Co., Ltd., Mitsubishi-Tanabe Pharma Co., Daiichi Sankyo Co., Ltd.; Financial Interests, Personal, Other, consultancy: Chugai Pharmaceutical Co.; Financial Interests, Research Grant: Chugai Pharmaceutical Co.; Financial Interests, Funding: Nippon Boehringer Ingelheim Co.,Ltd., Asahikasei Pharma Corp., Nippon Kayaku Co., Ltd. C. Qian: Financial Interests, Institutional, Full or part-time Employment: Shanghai Roche Pharmaceutical Ltd. N. Yamamoto: Financial Interests, Personal, Invited Speaker: MSD K.K, AstraZeneca, Ono Pharmaceutical CO., LTD., Daiichi Sankyo CO., LTD., Taiho Pharmaceutical CO., LTD., Takeda Pharmaceutical CO., LTD., Chugai Pharmaceutical CO., LTD., Eli Lilly Japan K.K., Novartis, Pfizer Inc., Amgen Inc., MercK biopharma; Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo CO., LTD., Takeda Pharmaceutical CO., LTD., Chugai Pharmaceutical CO., LTD., Eli Lilly Japan K.K., Novartis; Financial Interests, Institutional, Research Grant: MSD K.K; Financial Interests, Institutional, Local PI: AstraZeneca, Taiho Pharmaceutical CO., LTD., Takeda Pharmaceutical CO., LTD., Amgen Inc., Janssen Pharmaceutical K.K., Novartis, Eisai, Eli Lilly Japan; Financial Interests, Institutional, Funding: Daiichi Sankyo CO., LTD., Taiho Pharmaceutical CO., LTD., Chugai Pharmaceutical CO., LTD., Sanofi. All other authors have declared no conflicts of interest.