Abstract 639P
Background
PD-L1 inhibitors plus etoposide-platinum (EP) has become the standard of care in the first-line treatment of extensive stage-small cell lung carcinoma (ES-SCLC), but the efficacy is limited. Irinotecan-cisplatin (IP) is used in ES-SCLC, and irinotecan has been reported to have immunostimulatory activity. Here, we reported on REBORN trial (jRCT- 2051200125), the first phase II study to assess the efficacy and safety of IP plus durvalumab for untreated ES-SCLC.
Methods
This is a multicenter, single arm, phase II trial. Eligible patients were 20-74 years old with untreated ES-SCLC, with PS 0-1. Patients received four cycles of IP (irinotecan 60 mg/m2, days 1,8,15 and cisplatin 60 mg/m2, day 1) plus durvalumab 1500 mg followed by durvalumab 1500 mg every 4 weeks until disease progression (PD) or unacceptable toxicity. The primary endpoint is the 12-month progression-free survival (PFS) rate assessed by an independent central review (ICR). The secondary endpoints are PFS, overall survival (OS), objective response rate (ORR), and safety. We assumed the threshold of the 12-month PFS rate to be 18% and the expected rate to be 35% with a significance level α=0.05(one-sided) and power 0.8.
Results
Between May 2021 and Nov 2022, 42 patients were enrolled from 15 institutions in Japan. The median age was 66, 76.2% were male, 31.0% had PS 0. The 12-month PFS rate by ICR was 18.8% (90% CI, 9.3-30.8%) after a median follow-up of 14.5 months. ICR-assessed confirmed ORR was 65.9% (95% CI, 49.4-79.9%) and disease control rates of 85.4% (95% CI, 70.8-94.4%). Median PFS was 5.7 months (95% CI, 4.9-7.6 months) by ICR-assessed, and 5.7 months (95% CI, 5.4-7.6 months) by investigator-assessed. Median OS was 16.9 months (95% CI, 11.8-NE months), and the 12-month OS rate was 65.8% (95% CI, 49.1-78.1). Grade 3 or 4 adverse events (AEs) occurred in 69.0%, and grade 5 in 1 (2.4%) with pneumonitis and 1(2.4%) with hepatitis, which were immune-related AEs. Pneumonitis occurred in 4.8% (grade1, n=1; grade5, n=1) and diarrhea of grade 3 or more occurred in 7.1%.
Conclusions
This REBORN trial didn’t show the expected efficacy of IP plus durvalumab for untreated ES-SCLC. Efficacy and safety findings were consistent with those of EP plus durvalumab.
Clinical trial identification
jRCT- 2051200125.
Editorial acknowledgement
Legal entity responsible for the study
West Japan Oncology Group (WJOG).
Funding
AstraZeneca K.K.
Disclosure
M. Tachihara: Financial Interests, Personal, Invited Speaker: Eli Lilly Japan K.K., Chugai Pharmaceutical Co.,Ltd, AstraZeneca K.K, MSD K.K., Ono Pharmaceutical Co., Ltd., Bristol Myers Squibb Co. Ltd., Nippon Boehringer Ingelheim Co., Ltd., Pfizer Japan Inc., Daiichi Sankyo, Janssen Pharmaceutical K.K., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd.; Financial Interests, Institutional, Research Grant: AstraZeneca K.K., Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd. H. Shoda: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Chugai, Boehringer Ingelheim, Taiho, Eli Lilly, Bristol Myers Squibb, MSD, Merck BioPharma, Takeda and Life Technologies. M. Oki: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Novartis Pharma K.K., Eli Lilly Japan K.K.; Financial Interests, Personal, Research Funding: AbbVie Inc., MSD K.K., AstraZeneca K.K., Janssen Pharmaceutical K.K., Ono Pharmaceutical Co., Ltd., DAIICHI SANKYO Co., Ltd. Y. Sato: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharmaceutical, MSD, Ono Pharmaceutical, Novartis, Pfizer, Taiho Pharmaceutical, Nippon Kayaku, Bristol Myers Squibb, Eli Lilly, Takeda, Kyowa Kirin, Daiichi Sankyo, Boehringer Ingelheim. S. Sugawara: Financial Interests, Personal, Other, Lecture fee: AstraZeneca, Chugai Pharma, Nippon Boehringer Ingelheim, Taiho Pharmaceutical, Pfizer, Lilly, Novartis, Bristol Myers Squibb, Ono Pharmaceutical, MSD K.K, Kyowa Kirin, Takeda, Nippon Kayaku, Merck, Amgen, Thermo Fisher Scientific; Financial Interests, Personal, Other, Lecture Fee: Eisai, Sysmex; Financial Interests, Institutional, Local PI: AstraZeneca, Chugai Pharma, MSD K.K, Daiichi Sankyo, Bristol Myers Squibb, AnHeart, Ono Pharmaceutical, Nippon Boehringer Ingelheim, AbbVie, Parexel International, Amgen, Taiho Pharmaceutical, Accerise, A2 Healthcare, EPS Corporation, Syneos Health, PPD-SNBL. S. Ikeda: Financial Interests, Personal, Advisory Board: AstraZeneca, Chugai, Ono, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Ono, Bristol Myers Squibb, Taiho, Eli Lilly, Pfizer, Boehringer Ingelheim, Takeda, MSD; Financial Interests, Personal, Research Grant: AstraZeneca, Chugai. T. Yokoyama: Financial Interests, Personal, Research Funding: MSD, Chugai Pharmaceutical Co. Ltd, Bristol Myers Squibb Co. Ltd, Boehringer Ingelheim Japan Inc, Takeda Pharmaceutical Co. Ltd., Delta-Fly Pharma, Janssen Pharmaceutical K.K., AbbVie GK, Daiichi Sankyo Co. Ltd, Parexel International Inc.; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Chugai Pharmaceutical, Eli Lilly Japan, Pfizer Japan, Bristol Myers Squibb, Ono Pharmaceutical, Takeda Pharmaceutical, Nippon Kayaku, MSD, Novartis, Merck Biopharma. H. Kaneda: Financial Interests, Personal, Research Funding: Eli Lilly Japan K.K.; Financial Interests, Personal, Speaker’s Bureau: Chugai, MSD, Ono Pharmaceutical, Bristol Myers Squibb, AstraZeneca. S. Itoh: Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb K.K., AstraZeneca K.K., Amgen Inc., Chugai Pharmaceutical Co., Ltd., Pfizer Inc., Eisai Co., Ltd. A. Bessho: Financial Interests, Personal, Research Funding: AstraZeneca, Chugai Pharmaceutical, MSD; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Chugai Pharmaceutical, TAIHO Pharmaceutical, Bristol Myers Squibb, Ono Pharmaceutical, MSD. N. Katakami: Financial Interests, Personal, Invited Speaker: AstraZeneca, Takeda Pharmaceutical, Chugai Pharmaceutical, Kyorin Pharmaceutical, Bristol Myer Squib, Ono Pharmaceutical, Boehringer Ingelheim, Kyowa-Kirin, Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Local PI: Chugai Pharmaceutical. S. Morita: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca K.K., Bristol Myers Squibb Company, Chugai Pharmaceutical Co. Ltd, Eli Lilly Japan K.K, MSD K.K, Ono Pharmaceutical Co. Ltd. K. Nakagawa: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Nippon Boehringer Ingelheim Co., Ltd., Taiho Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., Incyte biosciences Japan, Merck Biopharma Co., Ltd., Janssen Pharmaceutical K.K., Bristol Myers Squibb Company, Medical Mobile Communications co., Ltd, Novartis Pharma K.K., Daiichi Sankyo Co., Ltd., Otuka Pharmaceutical Factory, Inc., M3, Inc., Hisamitsu Pharmaceutical Co., Inc., Global Health Consulting Japan Co., Ltd., The Yomiuri Shimbun; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K.; Financial Interests, Personal, Writing Engagement: Yodosha CO., LTD.; Financial Interests, Institutional, Research Grant: Amgen Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., EP-CRSU CO., LTD., EPS Corporation., Eisai Co., Ltd., GSK K.K., IQVIA Services JAPAN K.K., Janssen Pharmaceutical K.K., Kobayashi Pharmaceutical Co., Ltd., MSD K.K., Nippon Boehringer Ingelheim Co., Ltd., Nippon Kayaku Co.,Ltd., Pra Healthsciences, SRL Medisearch Inc., Syneos Health Clinical K.K., Sanofi K.K., Taiho Pharmaceutical Co.,Ltd., Takeda Pharmaceutical Co., Ltd., Cmic Co., Ltd., Pfizer R&D Japan G.K., Labcorp Development Japan K.K., Pfizer Japan Inc., Shionogi & Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Astellas Pharma Inc., Ascent Development Services, Eisai Inc., Bayer Yakuhin, Ltd, AstraZeneca K. K., AbbVie Inc., A2 Healthcare Corp., Japan Clinical Cancer Research Organization, Thoracic Oncology Research Group. 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. 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.