Abstract 409P
Background
While combinations of immune-checkpoint inhibitors (ICI) with chemotherapy have been approved for esophageal cancer, it remains unclear whether the immunochemotherapy (ICT) offers advantages compared to the simple addition of its individual monotherapies. The primary objective was to investigate whether the ICT exhibits a synergistic effect in advanced esophageal squamous cell carcinoma (ESCC) patients.
Methods
The reconstructed individual patient data was electronically extracted from the Kaplan-Meier curve of phase III randomized controlled trials (RCTs) using the following steps: scanning all time points on the curve where an event occurred, combining the number of survivors at each time point listed in the at-risk table, and applying a numerical algorithm to reconstruct the progression-free survival (PFS) time. The observed PFS curve of each constituent monotherapies was used to estimate simulated PFS curves expected under a model of independent drug action. If the observed curve demonstrated significantly better PFS than simulated curve, the combination of ICI and chemotherapy may have a synergistic effect, implying a superior outcome compared to simply adding the component monotherapy.
Results
The study included 3,330 unresectable advanced, recurrent, or metastatic ESCC patients from eight RCTs (ATTRACTION-3, CheckMate648, KEYNOTE-181, KEYNOTE-590, RATIONALE-302, RATIONALE-306, ESCORT and ESCORT-1st). The 1-year, 2-year and median PFS of the observed and simulated curves was 26.3% vs. 24.8%, 14.6% vs. 12.0%, and 6.9 months vs. 6.4 months, respectively. One sample log-rank test showed no significant differences between the observed and simulated curves (p = 0.073).
Conclusions
The observed PFS of ICT was comparable to the simulated PFS estimated from the data for each monotherapy. Although it was not clear whether potential synergies existed for ICT, these findings at least suggest that the benefits of ICI and chemotherapy are not offsetting each other, thereby providing a potential clinical rationale for the adoption of ICT in patients with advanced ESCC.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
K. Nagashima: Financial Interests, Personal, Other, Received consulting fees: Senju Pharmaceutical Co., Ltd., Toray Industries, Inc., Kowa Company, Ltd.; Financial Interests, Institutional, Other, Received consulting fees: Eli Lilly. S. Matsuda: Financial Interests, Personal, Speaker’s Bureau: MSD, Ono Pharmaceutical, BMS, Daiichi Sankyo, Olympus, Novartis. Y. Sato: Financial Interests, Personal, Invited Speaker: Eisai Co., Ltd; Financial Interests, Personal, Advisory Role: Mochida Pharmaceutical Co., Ltd. K. Hirata: Financial Interests, Personal, Invited Speaker: Eli Lilly Japan K.K., Taiho Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Bristol Myers Squibb Company, Yakult Honsha Co., Ltd.; Financial Interests, Personal and Institutional, Research Grant: Taiho Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Bristol Myers Squibb Company, Pfizer Inc. S. Yamamoto: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical, BMS, MSD, Taiho Pharmaceutical Co., Ltd., Covidien Japan, Inc.; Financial Interests, Personal, Advisory Role: Ono Pharmaceutical, Hokuto. M. Nomura: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical, BMS, MSD; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical. T. Tsushima: Financial Interests, Personal, Invited Speaker: Taiho Pharma, Ono Pharmaceutical, MSD, Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Taiho Pharma, MSD, Ono Pharmaceutical. H. Takeuchi: Financial Interests, Personal, Invited Speaker: Medtronic, EA Pharma Co., Ltd., Kaken Pharmaceutical Co., Ltd., Medicon, Otsuka Pharmaceutical, Otsuka Pharmaceutical Factory, Daiichi Sankyo, Taiho Pharmaceutical Co., Ltd., Tsumura Co., Ltd., Johnson & Johnson K.K., Ono Pharmaceutical, MSD, Abbott Japan LLC, Nichi-Iko Pharmaceutical Co., Ltd., Hisamitsu Pharmaceutical Co., Inc., Intuitive Surgical, Inc., Miyarisan Pharmaceutical Co., Ltd., BMS; Financial Interests, Personal, Research Grant: Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Kaken Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Eli Lilly Japan K.K., Daiichi Sankyo, Otsuka Pharmaceutical Factory, Johnson & Johnson K.K. 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 Biopharma, Amgen, Novartis; Financial Interests, Personal, Expert Testimony: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Ono Pharmaceuticals, Merck & Co, Bayer, AstraZeneca, BeiGene, Chugai, Taiho, Oncolys Biopharma, Janssen Pharmaceutical. Y. Kitagawa: Financial Interests, Personal, Research Grant: Asahi Kasei Pharma Corporation, Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Factory Inc., Nippon Covidien Inc., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Kaken Pharmaceutical Co., Ltd., EA Pharma Co., Ltd., Yakult Honsha Co. Ltd., Otsuka Pharmaceutical Co., Ltd., Tsumura & Co., Sumitomo Pharma Co., Ltd., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Limited., Cardinal Health, Kowa Company, Ltd.; Financial Interests, Personal, Invited Speaker: Asahi Kasei Pharma Corporation, AstraZeneca K.K., Ethicon Inc., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Factory, Inc., Olympus Corporation, Cardinal Health K.K., Shionogi & Co., Ltd., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Bristol Myers Squibb K.K., MSD K.K., Smith ＆ Nephew KK, Kaken Pharmaceutical Co., Ltd., 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. All other authors have declared no conflicts of interest.