1527P - GnP vs mFOLFIRINOX or S-IROX in metastatic pancreatic cancer: 1-year follow-up updated data from the GENERATE (JCOG1611)

Background

We previously reported that the superiority of modified FOLFIRINOX (mFOLFIRINOX) and S-IROX (S-1, irinotecan, and oxaliplatin) compared with Gemcitabine (G) plus nab-paclitaxel (nP) (GnP) were not demonstrated as first-line treatment for metastatic pancreatic cancer (MPC). We report the final follow-up updated data.

Methods

This randomized, open-label, phase 2/3 trial was done in 45 Japanese centers. Eligible patients (pts) were aged 20–75 years and had an ECOG PS of 0–1 with pathologically confirmed metastatic or recurrent pancreatic cancer. Pts were randomly allocated (1:1:1) to receive GnP (G 1,000 mg/m² and nP 125 mg/m² on days 1, 8, 15, every 4 weeks), mFOLFIRINOX (oxaliplatin 85 mg/m², irinotecan 150 mg/m²,and l-leucovorin 200 mg/m² on day 1, and 5-FU 2,400 mg/m² on days 1–3, every 2 weeks), or S-IROX (oxaliplatin 85 mg/m² and irinotecan 150 mg/m² on day 1, and S-1 80 mg/m²/day on days 1–7, every 2 weeks). The primary endpoint was overall survival (OS).

Results

From Apr 2019 to Mar 2023, 527 pts were included and analyzed for the final analysis. The median OS was 15.3 mo in the GnP arm, 12.5 mo in the mFOLFIRINOX arm (HR 1.27, 95% CI 1.01–1.61), and 13.2 mo in the S-IROX arm (HR 1.23, 95% CI 0.98–1.56). The median progression-free survival was 6.5 mo in the GnP arm, 5.9 mo in the mFOLFIRINOX arm (HR 1.06, 95% CI 0.86–1.32), and 6.0 mo in the S-IROX arm (HR 0.96, 95% CI 0.77–1.20). Subsequent anti-cancer therapy was administered in 85.8% of GnP arm, 86.9% of mFOLFIRINOX arm, and 87.5% of S-IROX arm. Nal-IRI-based regimens were administered as the 2nd-line setting in 22.2% of the GnP arm, 1.1% of the mFOLFIRINOX arm, and 0.6% of the S-IROX arm. In the BRCA mutated pts, OS was longer than that in wild type pts in all 3 arms (GnP 25.9 mo, mFOLFIRINOX 18.4 mo, S-IROX 33.2 mo). Grade 3 or higher anorexia was more frequent in the mFOLFIRINOX (22.8%) and S-IROX (27.6%) arm than in the GnP arm (5.2%).

Conclusions

In the final analysis as well as in the interim analysis, GnP is recommended as the first-line treatment for pts with MPC compared to mFOLFIRINOX or S-IROX.

Clinical trial identification

jRCTs031190009.

Editorial acknowledgement

Legal entity responsible for the study

Japan Clinical Oncology Group (JCOG), Hepatobiliary and Pancreatic Oncology Group (HBPOG).

Funding

Japan Agency for Medical Research and Development; National Cancer Center Research and Development.

Disclosure

S. Kobayashi: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Bayer Yakuhin, Eisai Pharmaceutical, Yakult Honsha, Servier Japan, Chugai Pharmaceutical, Eli Lilly Japan, Takeda Pharmaceutical, Otsuka Pharmaceutical, AstraZeneca, Ono Pharmaceutical, Merck Sharp & Dohme, Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Zymeworks. A. Ohba: Financial Interests, Personal, Invited Speaker: Yakult, Ono, Servier, Taiho, Eisai; Financial Interests, Personal, Advisory Board: Zymeworks; Financial Interests, Institutional, Local PI: Ono, Chugai, Novartis. M. Ozaka: Financial Interests, Personal, Invited Speaker: Taiho, Yakult, MSD, Incyte, Ono, Bayer, Servier. J. Mizusawa: Financial Interests, Personal, Other, Honoraria: Chugai Pharmaceutical, Taiho Pharmaceutical; Other, My spouse receives salary: Pfizer. T. Okusaka: Financial Interests, Personal, Advisory Board: Eisai, Nihon Servier, AstraZeneca, Fujifilm Toyama Chemical; Financial Interests, Personal, Invited Speaker: AstraZeneca, Eisai, Chugai Pharma, Nihon Servier, Incyte, Novartis, Daiichi Sankyo, Taiho, Yakult, Myriad Genetics, Kyowa Kirin, Ono; Financial Interests, Institutional, Local PI: AstraZeneca, Eisai, Bristol Myers Squibb, Incyte, Syneos Health, Chiome Bioscience, Sysmex. M. Ikeda: Financial Interests, Personal, Advisory Board: AstraZeneca, Chugai, Eisai, Nihon Servier, Novartis, Bristol Myers Squibb, MSD, Boehringer Ingelheim, Astellas Pharma, GSK; Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Eli Lilly Japan, Eisai, Nihon Servier, Novartis, Taiho, Yakult, Teijin Pharma, AbbVie, Fujifilm Toyama Chemical, Incyte Biosciences Japan, Takeda, Ono, MSD, Taisho Pharmaceutical, Nippon Kayaku, Guardant Health Japan, Nobelpharma; Financial Interests, Institutional, Coordinating PI: Bayer, Bristol Myers Squibb, Eisai, AstraZeneca, Eli Lilly Japan, Chugai Pharmaceutical, MSD, Ono, Novartis, J-Pharma, Chiome Bioscience, Nihon Servier, Delta-Fly Pharma, Syneos Health, Merus. N.V., Merck Biopharma, Boehringer Ingelheim, Invitae, Nobelpharma; Financial Interests, Personal, Steering Committee Member: Chugai, Nihon Servier, Takeda, Novartis, Eisai, Rakuten Medical. N. Sasahira: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Eisai, Chugai Pharmaceutical, Takeda Pharmaceutical, AstraZeneca; Financial Interests, Institutional, Funding: Taiho Pharmaceutical, Chugai Pharmaceutical, Daiichi Sankyo, Shionogi, Teijin Pharma. K. Ikezawa: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Yakult Honsha, MSD, Myriad Genetics, Asahi Kasei Pharma, Incyte Biosciences Japan, Nihon Servier, Chugai Pharmaceutical, AstraZeneca. N. Okano: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Eli Lilly Japan, Eisai, Bayer Yakuhin, Chugai Pharma, Ono Pharmaceutical, Daiichi Sankyo, AstraZeneca, MSD, Incyte, Nihon Servier; Financial Interests, Personal, Funding: J-Pharma. N. Mizuno: Financial Interests, Personal, Invited Speaker: Yakult Honsha, AstraZeneca, Novartis, Fujifilm Toyama Chemical, Taiho Pharmaceutical, Miyarisan Pharmaceutical; Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim; Financial Interests, Institutional, Local PI: MSD, Incyte, Ono Pharmaceutical, Seagen, Boehringer Ingelheim, Pfizer, AstraZeneca, Servier; Financial Interests, Institutional, Coordinating PI: Novartis. H. Katayama: Financial Interests, Personal, Invited Speaker: Fujifilm cooperation. J. Furuse: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical, Bayer, Eisai, Eli Lilly Japan, MSD, Yakult Honsha, Chugai Pharma, Novartis Pharma, AstraZeneca, Pfizer, Takeda, Taiho Pharmaceutical, Sanofi, Mylan EPD, EA Pharma, Kyowa Hakko Kirin, Daiichi Sankyo, Teijin Pharma, Servier Japan, Incyte; Financial Interests, Personal, Advisory Board: Fuji film, Mundi Pharma, Onco Therapy Science, Merck Bio, Ono Pharmaceutical, MSD, Taiho Pharmaceutical, Chugai Pharma, Astellas, AstraZeneca, Takara Bio, Delta-Fly-Pharma, Incyte Japan; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical, MSD, Merck Bio, J-Pharma, Taiho Pharmaceutical, Takeda, Chugai Pharma, AstraZeneca, Yakult Honsha, Eisai, Daiichi Sankyo, Mochida, Sanofi, Sumitomo Dainippon Bayer, Astellas, Incyte Japan; Financial Interests, Personal, Steering Committee Member: Merck Bio, Ono Pharmaceutical, MSD, Taiho Pharmaceutical, Astellas, AstraZeneca, Incyte Japan. M. Ueno: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharmaceutical, Incyte, MSD, Nihon Servier, Ono Pharmaceutical, Taiho Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, J-Pharma, Eisai, Yakult Honsha; Financial Interests, Personal, Advisory Board: Nippon Boehringer Ingelheim, Novartis; Financial Interests, Institutional, Local PI: Astellas Pharma, AstraZeneca, Chugai Pharmaceutical, DFP, Daiichi Sankyo, Eisai, Incyte, MSD, Merck Biopharma, Ono Pharmaceutical, Taiho Pharmaceutical, Novartis, J-Pharma, Novocure, Chiome Bioscience. All other authors have declared no conflicts of interest.