1788P - Final overall survival analysis of JCOG1205/1206: Phase III study of irinotecan/cisplatin (IP) versus etoposide/cisplatin (EP) for completely resected high-grade neuroendocrine carcinoma (HGNEC) of the lung

Background

In the WHO classification, small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) are considered as high-grade neuroendocrine carcinoma (HGNEC) of the lung. JCOG1205/1206 has failed to show the superiority of IP to EP in relapse-free survival (RFS) for patients with completely resected HGNEC. Overall survival (OS) is one of important secondary endpoints in this study.

Methods

Patients with completely resected HGNEC were randomized in a 1:1 ratio to receive either etoposide (100 mg/m², days 1-3)/cisplatin (80 mg/m², day 1) or irinotecan (60 mg/m², days 1, 8, 15)/cisplatin (60 mg/m², day 1), using the minimization method according to sex, pathologic stage, histology and institution. This analysis was performed by using data at 5 years after last patient enrolment. In addition, central pathological reviews (CPR) were planned in this study.

Results

Between April 2013 and October 2018, 221 patients with a median age of 66 years, pathological stage I (54%), SCLC (53%), were randomly assigned to the EP arm (n = 111) or the IP arm (n = 110). Updated 3-year and 5-year RFS were 68.5% and 65.7% in the EP arm versus 71.8% and 65.2% in the IP arm, with a hazard ratio (HR) of 1.026 (95% CI, 0.670-1.569). With a median follow-up of 71.0 months, OS at 3 years and 5 years were 85.6% and 73.5% in the EP arm versus 83.6% and 72.4% with HR of 1.175 (95% CI, 0.742-1.861). In the subgroup analyses of histology by pathologist at institution, 5-year OS in SCLC was 69.5% versus 70.7% with HR of 1.023 (95% CI, 0.554-1.889), and 5-year OS in LCNEC was 78.0% versus 74.5% with HR of 1.352 (95% CI, 0.672-2.720). Concordance proportion of pathological diagnosis between each institution and CPR was 75.6% (95% CI, 69.4-81.1%). 35 patients (31.5%) in EP arm and 35 patients (31.8%) in IP arm received subsequent treatment. Secondary cancers occurred in 22 patients (19.8%) in EP arm, and 17 patients (15.5%) in IP arm.

Conclusions

This final analysis showed no significant difference in both updated RFS and OS between two arms for patients with completely resected HGNEC, with 5-year OS >70%.

Clinical trial identification

jRCTs031180216.

Editorial acknowledgement

Legal entity responsible for the study

Japan Clinical Oncolgoy Group.

Funding

AMED.

Disclosure

S. Niho: Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Ono, Chugai, Eli Lilly, Takeda, Merck Biopharma, Eisai, Novartis, Kyorin, Boehringer Ingelheim, Kyowa Kirin, MSD, Nippon Kayaku, Daiichi Sankyo, Amgen; Financial Interests, Institutional, Funding: Taiho, GSK, Daiichi Sankyo, Chugai, Teijin, Eli Lilly, Kyowa Kirin, Shionogi, Boehringer Ingelheim, Kyorin, Nippon Kayaku. H. Kenmotsu: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co, Ltd., Ono Pharmaceutical Co, Ltd., Boehringer Ingelheim, Eli Lilly K.K, Kyowa Hakko Kirin Co., Ltd., Bristol Myers Squibb, MSD, Novartis Pharma K.K., Daiichi Sankyo Co., Ltd., AstraZeneca K.K., Pfizer, Taiho Pharma, Merck, Amgen inc., Bayer, Takeda Pharmaceutical Co., Ltd, Guardant health Japan; Financial Interests, Institutional, Research Grant: AstraZeneca, Chugai Pharmaceutical Co, Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co, Ltd., LOXO Oncology, Eli Lilly K.K; Non-Financial Interests, Principal Investigator: AstraZeneca K.K., Eli Lilly K.K, Boehringer Ingelheim, Takeda Pharmaceutical Co., Ltd. M. Tsuboi: Financial Interests, Personal, Invited Speaker, Lecture: Johnson & Johnson Japan; Financial Interests, Personal, Advisory Board, Lectures, Advisory boards: AstraZeneca KK, Chugai Pharmaceutical CO.,LTD, MSD; Financial Interests, Personal, Invited Speaker, Lectures: Eli Lilly Japan, Bristol Myers Squibb KK, Taiho Pharma, Medtronic Japan, ONO Pharmaceutical CO.,LTD, Daiichi Sankyo company limited; Financial Interests, Personal, Advisory Board, Advisory boards: Novartis, MiREXS; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim Japan, MSD, AstraZeneca KK, Ono Pharmaceutical CO.,LTD, Bristol Myers Squibb KK, Novartis, MiRXES; Financial Interests, Personal, Steering Committee Member: MSD, AstraZeneca, Novartis; Financial Interests, Institutional, Steering Committee Member: Eli Lilly Japan. M. Wakabayashi: Financial Interests, Personal, Speaker, Consultant, Advisor: Nihon Medi-Physics. G. Ishii: Financial Interests, Institutional, Funding: Daiichi Sankyo, ONO PHARMACEUTICAL, Noile-Immune Biotech, Takeda, Sumitomo Dainippon Pharma, Nihon Medi-Physics, Indivumed GmbH, H.U. Group Research Institute; Financial Interests, Personal, Speaker, Consultant, Advisor: Takeda, Roche Diagnostics, Chugai, Novartis International AG, Eli Lilly Japan K.K., AstraZeneca, Riken Genesis, Merck Biopharma Japan. H. Asahina: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical, AstraZeneca, MSD, Ono Pharmaceutical, Kyowahakko Kirin, Eli Lilly, Merck; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Research Grant: AstraZeneca. Y. Nakamura: Financial Interests, Institutional, Funding: AstraZeneca, MSD, Bristol Myers Squibb. K. Naoki: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Chugai. K. Nishino: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical CO., LTD., MSD, Amgen, Janssen Pharmaceutical K.K., Novartis Pharmaceuticals, Pfizer, Eli Lilly Japan, Merck Biopharma Co., Ltd., Takeda Pharmaceutical Co.,Ltd., Chugai pharmaceutical, AstraZeneca, Nippon Boehringer Ingelheim, Daiichi Sankyo Company, Limited, Nippon Kayaku Co.,Ltd., Daiichi Sankyo Co., Ltd., Mochida Pharmaceutical Co., Ltd., Yuyu Teijin Medicare Inc., Varian Medical Systems, Inc.; Financial Interests, Personal, Advisory Board: Pfizer, Janssen Pharmaceutical K.K., AstraZeneca; Financial Interests, Institutional, Coordinating PI: Ono Pharmaceutical CO., LTD., Taiho Pharmaceutical CO., LTD., MSD, AbbVie, Daiichi Sankyo Company, Limited, Amgen, Eli Lilly, Eisai Co., Ltd., Sanofi K.K., Janssen Pharmaceutical K.K., Novartis Pharmaceuticals, Pfizer, Merck Biopharma Co., Ltd., Takeda Pharmaceutical Co.,Ltd., Chugai pharmaceutical, Merus, AstraZeneca. T. Yokoyama: Financial Interests, Institutional, Funding: AbbVie GK, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Delta-Fly Pharma, Janssen, MSD, Parexel International, Takeda; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Bristol Myers Squibb, Chugai Pharmaceutical, Eli Lilly, Merck Biopharma, MSD, Nippon Kayaku, Novartis, Ono Pharmaceutical, Pfizer, Takeda. H. Asamura: Financial Interests, Institutional, Funding: Taiho, Johnson and Johnson, Medtronic ; Financial Interests, Personal, Speaker, Consultant, Advisor: Johnson and Johnson, Medtronic Japan. 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. All other authors have declared no conflicts of interest.