1203P - Role of tumor markers before or during chemotherapy for poorly differentiated neuroendocrine carcinomas of the digestive system: An exploratory analysis of JCOG1213

Background

Poorly differentiated neuroendocrine carcinomas (PDNECs) are high-grade neuroendocrine neoplasms with an extremely poor prognosis. Previously, we reported the results of a randomized phase 3 trial (JCOG1213), which compared between etoposide plus cisplatin and irinotecan plus cisplatin in patients with neuroendocrine carcinomas (WHO 2010) of the digestive system, showing a statistically non-significant difference in overall survival. It is unclear whether tumor markers (TM), such as NSE and ProGRP, can be predictors or monitoring indicators of the efficacy in PDNEC treatment. This exploratory analysis using the data from JCOG1213 aimed to evaluate whether 1) pre-treatment TM levels can predict treatment efficacy and 2) the change in TM levels after treatment initiation is relevant to treatment efficacy.

Methods

In 137 patients with a central pathological diagnosis of PDNECs out of 170 patients enrolled in JCOG1213, the following analyses were performed: 1) association between pre-treatment NSE/ProGRP levels (elevated or normal with the cutoff of 10 ng/mL in NSE and 46 ng/mL in ProGRP) and tumor response (RECIST v1.1), 2) association between response and the change (increased or decreased) from baseline in NSE/ProGRP at 6 weeks after treatment initiation was evaluated.

Results

1) Pre-treatment NSE levels were elevated/normal in 127/9 patients and ProGRP levels were elevated/normal in 74/60 patients. There were no meaningful difference in terms of response rate: 58%/56% in patients with elevated/normal NSE and 61%/57% in patients with elevated/normal ProGRP. 2) The response rates were 65% (68/104) in patients with decreased NSE and 32% (8/25) in patients with increased NSE (p=0.0043). The response rates in patients with decreased/increased ProGRP were 68% (43/63)/52% (32/62).

Conclusions

In patients with PDNEC of the digestive system, pre-treatment NSE/ProGRP levels was not associated with tumor response. As treatment monitoring indicators, changes in NSE may be more relevant to tumor response than ProGRP.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Japan Clinical Oncology Group.

Funding

Has not received any funding.

Disclosure

T. Satake: Financial Interests, Institutional, Local PI: ONO, Nihon Servier. C. Morizane: Financial Interests, Personal, Advisory Board: Yakult, MSD, Servier, Boehringer Ingelheim, AstraZeneca, Taiho Pharmaceutical, Merck biopharma; Financial Interests, Personal, Invited Speaker: Novartis, Teijin Pharma; Financial Interests, Institutional, Coordinating PI: Yakult Honsha, ONO Pharmaceutical, Taiho Pharmaceutical, Eisai, MSD K.K., J-Pharma, AstraZeneca, Merck biopharma; Financial Interests, Institutional, Funding: Daiichi Sankyo RD Novare, Hitachi. N. Machida: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Ono, Taiho, MSD, Daiichi Sankyo, Yalult, Eli lilly Japan, Chugai, Astellas, Takeda, Merck biopharma, Nichi-iko, nippon-kayaku; Financial Interests, Institutional, Local PI: Bristol Myers Squibb, Ono, Daiichi Sankyo, Astellas, MSD, Amgen, ALX Oncology, Seagen. Y. Honma: Financial Interests, Institutional, Research Grant: Japan Agency for Medical Research and Development; Financial Interests, Personal, Invited Speaker: Novartis, Chugai Pharma, MSD, Eisai, Nutri, Ono pharmaceutical, BMS, Merch biopharma, Eli Lilly; Financial Interests, Personal, Advisory Board: Janssen, Eisai, Rakuten medical. T. Okusaka: Financial Interests, Personal, Advisory Board: AstraZeneca, Eisai, FUJIFILM Toyama Chemical, Nihon Servier, Dainippon Sumitomo Pharma, Toyama Chemistry, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharma, Eli Lilly, Incyte, Nihon Servier, Ono Pharmaceutical, Yakut Honsha, Daiichi Sankyo, Taiho Pharmaceutical; Financial Interests, Institutional, Local PI: AstraZeneca, Bristol Myers Squibb, Chugai Pharma, Dainippon Sumitomo Pharma, Eisai, Incyte, MSD, Novartis; Financial Interests, Personal, Steering Committee Member: AstraZeneca, Bristol Myers Squibb; Financial Interests, Institutional, Research Funding: AstraZeneca, Bristol Myers Squibb, Eisai, Incyte, Syneos Health/Immunocore. N. Boku: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Eli Lily, ONO Pharmaceutical, Taiho Pharma, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Takeda Pharmaceutical, ONO Pharmaceutical. K. Kato: Financial Interests, Personal, Invited Speaker: ONO Pharmaceutical, Bristol Myers Squibb, Merck and Co; Financial Interests, Personal, Advisory Board: ONO Pharmaceutical, Bristol Myers Squibb, Merck and Co, Bayer, AstraZeneca, BeiGene, Taiho, Merck Biophrma, Amgen, Novartis, Daiichi Sankyo; Financial Interests, Institutional, Coordinating PI: ONO Pharmaceuticals, Merck & Co; Financial Interests, Institutional, Local PI: Bayer, AstraZeneca, BeiGene, Chugai, Taiho, Oncolys Biopharma, JANSSEN Pharmaceutical. H. Imaoka: Financial Interests, Personal, Invited Speaker: Yakult Honsha, AstraZeneca, Nihon Servier, Kaneka Medix; Financial Interests, Personal, Advisory Board: Nihon Servier; Financial Interests, Institutional, Coordinating PI: Ono Pharmaceutical. S. Kobayashi: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Bayer Yakuhin, Eisai Pharmaceutical, Yakult Honsha, Servier Japan, GSK, Chugai Pharmaceutical, Eli Lilly Japan, Takeda Pharmaceutical, Otsuka Pharmaceutical, AstraZeneca; Financial Interests, Personal, Advisory Board: Zymeworks. T. Terashima: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca, Eisai, Chugai, Bayer, Taiho, Novartis, Teijin. M. Ikeda: Financial Interests, Personal, Advisory Board: AstraZeneca, Chugai, Eli Lilly Japan, Eisai, Nihon Servier, Novartis, MSD; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bayer, Bristol Myers Squibb, Chugai, Eli Lilly Japan, Eisai, Nihon Servier, Novartis, Taiho, Yakult, Teijin Pharma, AbbVie, Abbott Japan, FUJIFILM Toyama Chemical, Incyte Biosciences Japan, Takeda, Ono, MSD, Taisho Pharmaceutical, Nippon Kayaku, Guardant Health Japan; Financial Interests, Institutional, Coordinating PI: Bayer, Bristol Myers Squibb, Eisai, AstraZeneca, Eli Lilly Japan, Chugai Pharmaceutical, MSD, Ono, Novartis, J-Pharma, Pfizer, Chiome Bioscience, Nihon Servier, Delta-Fly Pharma, Syneos Health, Merus.N.V., Merck biopharma, Boehringer Ingelheim, Invitae; Financial Interests, Personal, Steering Committee Member: Chugai, Nihon Servier, Takeda, Novartis. N. Okano: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Eli Lilly Japan, Eisai, Bayer, Chugai Pharma, Ono Pharmaceutical, Takeda, Daiichi Sankyo, AstraZeneca. K. Yamaguchi: Financial Interests, Personal, Invited Speaker: Taiho Pharm; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Bristol Mayers Squibb, Ono Pharm, Eli Lilly Japan; Financial Interests, Institutional, Funding: Taiho Pharm. N. Mizuno: Financial Interests, Personal, Invited Speaker: Yakult Honsha, AstraZeneca, Novartis, FUJIFILM Toyama Chemical, Taiho Pharmaceutical; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Local PI: MSD, Incyte, Ono Pharmaceutical, Seagen; Financial Interests, Institutional, Coordinating PI: Novartis. Y. Kitagawa: Financial Interests, Personal, Invited Speaker: Asahi Kasei Pharma Corporation, AstraZeneca Japan, Bristol Myers Squibb K.K., Chugai Pharma, MSD K.K., Kaken Pharmaceutical, Nippon Covidien, Olympus, Otsuka, Cardinal Health K.K., Shionogi, Smith & Nephew, Taiho Pharmaceutical, ASKA Pharmaceutical Co., Ltd., Miyarisan Pharmaceutical Co. Ltd., Toray Industries, Inc., Daiichi Sankyo Company, Limited, Chugai Foundation for Innovative Drug Discovery Science, Nippon Kayaku Co., Ltd, EA Pharma Co.,Ltd, Intuitive Surgical G.K., Takeda Pharmaceutical Company Limited, Sysmex Corporation, Tsumura & Co.; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb K.K., Ono Pharmaceutical; Financial Interests, Institutional, Funding: Asahi Kasei Pharma Corporation, Chugai Pharma, EA Pharma, Eisai , Kaken Pharmaceutical, Kyouwa Kirin Co., Ltd., Nippon Covidien, Ono Pharmaceutical, Otsuka Pharmaceutical Co., Ltd., Taiho Pharmaceutical, Takeda, Teijin Pharma, Tsumura & Co., Yakult Honsha, Otsuka Pharmaceutical Factory Inc., Sumitomo Pharma Co., Ltd., Cardinal Health., Kowa Company, Ltd.. M. Terashima: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Chugai Pharma, Daiichi Sankyo, Intuitive Surgical, Johnson & Johnson, Lilly, Medtronic, Olympus, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, Takeda, Yakult Honsha; Financial Interests, Institutional, Research Funding: Ono Pharmaceutical. M. Ueno: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharmaceutical, Incyte, MSD, Nihon Servier, Ono Pharmaceutical, Taiho Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical; Financial Interests, Personal, Advisory Board: Nippon Boehringer Ingelheim; Financial Interests, Institutional, Local PI: Astellas Pharma, AstraZeneca, Chugai Pharmaceutical, DFP, Daiichi Sankyo, Eisai, Incyte, MSD, Merck Biopharma, Ono Pharmaceutical, Taiho Pharmaceutical, Novartis. All other authors have declared no conflicts of interest.