1521P - Efficacy and safety of liposomal irinotecan plus S-1 in patients with metastatic pancreatic cancer after failure of first-line gemcitabine-based chemotherapy: Result of a phase I/II study

Background

S-1, an oral fluoropyrimidine anticancer drug, demonstrated efficacy in patients with unresectable pancreatic cancer (PC). Thus, the liposomal irinotecan (nal-IRI) plus S-1 regimen (in which the 5-FU/LV in the nal-IRI+5-FU/LV regimen is replaced with S-1) not only improves the convenience of treatment, as it obviates the need for an intravenous port system, but may also exert stronger anticancer effects. Therefore, we conducted this phase I/II study to evaluate the safety and efficacy of nal-IRI plus S-1 for the treatment of metastatic PC after gemcitabine-based chemotherapy.

Methods

The primary endpoint in the phase I part of the study was the frequency of dose-limiting toxicities, and that of the phase II part was the overall survival (OS). The secondary endpoints included the objective response rate (ORR), progression-free survival (PFS), and safety.

Results

The recommended doses for the phase II part (nal-IRI: 70 mg/m² on day 1; S-1: 80-120 mg/day on days 1-7) were based on the dose-limiting toxicities observed during cycles 1 and 2 in the phase I part of the study (n = 12). In all, 49 of 55 patients received the recommended doses, including 6 patients in the phase I part of the study and 43 patients in the phase II part of the study (median age, 71.0 years [range, 40-80]; 25 [58.1%] patients had an ECOG performance status 1). The results were as follows: median OS, 10.3 months (95% confidence interval [CI], 8.1-12.0 months); median PFS, 5.7 months (95% CI, 4.4-7.3 months); and ORR, 20.4% (95% CI, 10.2%-34.3%). The most common treatment-related adverse events (TRAE) were neutrophil count decreased (75.5%), anorexia (69.4%), and platelet count decreased (59.2%). The most common ≥grade 3 TRAEs were neutrophil count decreased (20.4%), anorexia (18.4%), and hypokalemia (16.3%).

Conclusions

nal-IRI plus S-1 is a feasible regimen with a manageable safety profile and promising antitumor activity against metastatic PC after failure of first-line gemcitabine-based chemotherapy; therefore, the regimen warrants further evaluation.

Clinical trial identification

jRCTs031210040; Release date, Apr 15, 2021.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Servier.

Disclosure

H. Imaoka: Financial Interests, Personal, Invited Speaker: Yakult Honsha, AstraZeneca, Nihon Servier, Kaneka Medix, SB Kawasumi Laboratories, Boston Scientific, Novartis; Financial Interests, Personal, Advisory Board: Nihon Servier, Kaneka Medix; Financial Interests, Personal, Writing Engagement: Medico's Hirata; Financial Interests, Institutional, Local PI: Ono Pharmaceutical, Novartis, Nihon Servier. 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. M. Ozaka: Financial Interests, Personal, Invited Speaker: Taiho, Yakult, MSD, Incyte, Ono, Bayer, Servier. 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. S. Shimizu: Financial Interests, Institutional, Local PI: AstraZeneca, Incyte Corporation, Delta-Fly Pharma, Nihon Servier. Y. Komatsu: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., Ltd., Daiichi Sankyo, Taiho, Chugai, Lilly, Merck, MSD, BMS, Takeda, Bayer Yakuhin, Moroo Co., Asahi Kasei, Pfizer, Nippon Zoki Pharmaceutical Co., Ltd., EA Pharma Co., Ltd., Incyte Corporation, Zeria Pharmaceutical Co., Ltd., Yakult Honsha, Nipro Corporation, Sanofi/Aventis, Astellas Pharma Inc., Nippon Kayaku Co. Ltd.; Financial Interests, Personal, Writing Engagement: Eli Lilly and Company, Yakult Honsha Co., Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Company, Limited, Ono Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd.; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical Co., Ltd., Taiho, Chugai, Sanofi, Nipro, Daiichi Sankyo, BMS, Sysmex Corporation, EPS Holdings, Inc., Asahi Kasei Pharma Corporation, Nippon Zoki Pharmaceutical Co., Ltd., Nippon Kayaku Co. Ltd.; Non-Financial Interests, Member: JSCO, JSMO, ASCO. F. Hedouin-Biville: Financial Interests, Personal, Full or part-time Employment: Servier. 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.