Abstract
Background
Combination therapy with immune checkpoint inhibitors (ICIs) and chemotherapy (ICI + chemotherapy) has become the standard first line treatment for driver oncogene-negative advanced non-small-cell lung cancer (NSCLC). However, it may be more toxic compared to monotherapy, which limits its use. Moreover, the feasibility of the combination therapy in clinical practice remains unknown.
Methods
We conducted a cohort study to determine the implementation rate of ICI + chemotherapy in clinical practice. We retrospectively reviewed clinical data from advanced NSCLC patients who received systemic therapy at 13 institutions between December 2018 and December 2020.
Results
After excluding 154 patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) gene alterations, a total of 919 NSCLC patients were included. Among them, 442 were treated with ICI + chemotherapy (48%), whereas 477 were treated with other therapies (52%). Among these 477 patients, 340 did not receive ICI + chemotherapy because of intolerance (71%); thus, more than one-third of the advanced NSCLC patients do not benefit from the combination therapy due to intolerance. Among the 659 NSCLC patients for whom PD-L1 was < 50% or unknown, only 342 received the ICI + chemotherapy combination (52%) even though it is considered preferable to either therapy alone; the remaining 318 patients were treated with other therapies (48%). Among the 318 patients who did not receive ICI + chemotherapy, 274 were intolerant to it (86%).
Conclusion
Our results revealed that a substantial proportion of advanced NSCLC patients did not benefit from ICI + chemotherapy due to intolerance. As treatments for NSCLC are moving toward combinations for greater efficacy, their feasibility in clinical practice must be taken into consideration.
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Conception and design: EI; data acquisition: CA, TY, KI, TT, KF, NO, HK, DK, KW, MI, NO, FO, HI, HK, and ST; data analysis and interpretation: EI, KH, YM and KK; writing and/or review of manuscript: all the authors.
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Eiki Ichihara received honoraria from AstraZeneca K.K., Novartis, Janssen Pharmaceutical K.K., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K., Pfizer, Bristol-Myers Squibb Co. Ltd., Ono Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., and Boehringer Ingelheim. Eiki Ichihara received research funding from Janssen Pharmaceutical K.K., Pfizer, Bristol-Myers Squibb Co. Ltd., Ono Pharmaceutical Co. Ltd., and Takeda Pharmaceutical Co. Ltd. Toshihide Yokoyama received honoraria from AstraZeneca K.K., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K., Pfizer Japan Inc, Bristol-Myers Squibb Co. Ltd., Ono Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Nippon Kayaku Co., Ltd., Boehringer Ingelheim Japan Inc. Toshihide Yokoyama also recieved research funding from MSD, Takeda Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Bristol-Myers Squibb Co. Ltd., Boehringer Ingelheim Japan Inc. Koji Inoue received honoraria from AstraZeneca, Takeda, Shionogi, Kyowa Kirin, Ono, Towa, Chugai and Boehringer ingelheim. Tomoki Tamura received honoraria from Chugai Pharmaceutical Co., Ltd, and Taiho Pharmaceutical Co., Ltd. Keiichi Fujiwara received honoraria from MSD, AstraZeneca, Ono Pharmaceutical Co., Sanofi, and Eli Lilly Japan. Hirohisa Kano received honoraria from Boehringer Ingelheim, AstraZeneca, Bristol-Myers Squibb and ONO Pharmaceutical. Masaaki Inoue received honoraria from Bristol Myers Squibb, Chugai Pharmaceutical Co, Daiichi-Sankyo, Kyowa Kirin Co, AstraZeneca and Taiho Pharmaceutical Co. Hiroshi Kobe received honoraria from Boehringer ingelheim and Chugai pharmaceutical. Katsuyuki Hotta received honoraria from MSD, AstraZeneca, Chugai pharmaceutical, Lilly, BMS and Abbvie. He also received research funding from Pfizer, AstarZeneca, Chugai pharmaceutical, Lilly, Takeda Pharmaceutical, MSD, BMS, Ono pharmaceutical, Taiho pharmaceutical and Boehringer ingelheim. Yoshinobu Maeda received honoraria from AstraZeneca K.K., Amgen K.K., ONO pharmaceutical co., LTD., Bristol-Myers Squibb K.K., Takeda Pharmaceutical ltd., Chugai Pharmaceutical Co.,Ltd., Novartis, Pfizer Japan Inc., and Janssen Pharmaceutical K.K. Yoshinobu Maeda also received reserch funding from Chugai Pharmaceutical Co.,Ltd., AstraZeneca K.K., Novartis and Janssen Pharmaceutical K.K. Katsuyuki Kiura received honoraria from AstraZeneca, Novartis, Lilly, Taiho Pharmaceutical Co. td., Chugai Pharmaceutical, Pfizer, Ono pharmaceutical, MSD, BMS, Boehringer ingelheim, Daiichi Sankyo, Takeda and Nippon Kayaku. He also received research funding from Merk BioPharma, Kyowa Kirin, Pfizer, MSD, Boehringer ingelheim, Shionogi pharmaceutical, and Ono pharmaceutical.
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Supplementary file2 Table S1. Details of intolerance in all the investigated patients. Table S2. Details of intolerance in PD-L1<1% or unknown NSCLC patients. Table S3. Details of intolerance in PD-L1≥50% NSCLC patients (DOC 50 KB)
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Ando, C., Ichihara, E., Yokoyama, T. et al. More than one-third of advanced non-small-cell lung cancer patients do not receive immunochemotherapy due to intolerance. J Cancer Res Clin Oncol 149, 4933–4938 (2023). https://doi.org/10.1007/s00432-022-04415-1
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DOI: https://doi.org/10.1007/s00432-022-04415-1