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Impact of weight loss on treatment with PD-1/PD-L1 inhibitors plus chemotherapy in advanced non-small-cell lung cancer

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Abstract

Purpose

Programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors plus chemotherapy have become the standard first line of treatment in patients with advanced non-small-cell lung cancer (NSCLC). However, few studies have explicitly focused on the impact of weight loss on the efficacy of PD-1/PD-L1 inhibitors plus chemotherapy. Thus, we evaluated the clinical implications of weight loss on the survival outcomes in patients who received this treatment.

Methods

We conducted a retrospective review of medical records of patients with advanced NSCLC who were treated with PD-1/PD-L1 inhibitors plus chemotherapy from December 2018 to December 2020. Significant weight loss was defined as an unintentional weight loss of 5% or more over 6 months. We evaluated the progression-free survival (PFS) and overall survival (OS) of patients with or without weight loss.

Results

Among the 80 included patients, 37 (46%) had weight loss, and were associated with a lower objective response rate (30 vs 51%, P < 0.05), poorer PFS (2.3 vs 12.0 months, P < 0.05), and poorer OS (10.8 vs 23.9 months, P < 0.05) than those without weight loss. The Cox proportional-hazard ratios (95% confidence interval) of weight loss were 1.77 (1.01–3.10) for PFS and 2.90 (1.40–6.00) for OS, with adjustments for Eastern Cooperative Oncology Group performance status, PD-L1 tumour proportion score, histology, and central nervous system metastases.

Conclusion

Pre-treatment weight loss may reduce treatment efficacy and shorten survival time in patients receiving PD-1/PD-L1 inhibitors plus chemotherapy. Early evaluation and intervention for weight loss might improve oncological outcomes in patients with advanced NSCLC.

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Data availability

All data and material are available on reasonable request.

Code availability

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Author information

Authors and Affiliations

  1. Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan

    Taichi Miyawaki, Tateaki Naito, Michitoshi Yabe, Hiroaki Kodama, Naoya Nishioka, Eriko Miyawaki, Nobuaki Mamesaya, Haruki Kobayashi, Shota Omori, Kazushige Wakuda, Akira Ono, Hirotsugu Kenmotsu, Haruyasu Murakami & Toshiaki Takahashi

  2. Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan

    Taichi Miyawaki & Kazuhisa Takahashi

  3. Division of Clinical Research Management Office, Shizuoka Cancer Center, Shizuoka, Japan

    Keita Mori

  4. Radiation and Proton Therapy Center, Shizuoka Cancer Center, Shizuoka, Japan

    Hideyuki Harada

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  1. Taichi Miyawaki
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Contributions

TM and TN wrote the manuscript and researched data. TN reviewed and edited the manuscript. KM is a professional biostatistician and responsible for statistical analysis. All authors reviewed, approved the final version of the manuscript, and certified that they comply with the ethical guidelines for publishing in the Supportive care in Cancer.

Corresponding author

Correspondence to Tateaki Naito.

Ethics declarations

Ethics approval

The ethical review board of our institution approved the study (registration no. J2020-176–2020-1). All procedures performed in studies involving human participants were in accordance with 1964 Helsinki declaration and its later amendments or with comparable ethical standards.

Consent to participate

For this type of study, formal consent is not required. However, we also employed an opt-out method to obtain consent for this study by posting a document about this study. The document has been approved by the institutional ethics review board of Shizuoka Cancer Center.

Consent for publication

Not applicable.

Conflict of interest

Dr. Taichi Miyawaki — Declarations of interest: none.

Dr. Naito, Dr. Yabe, Dr. Kodama, Dr. Nishioka, Dr. Eriko Miyawaki, Dr. Mori — Declarations of interest: none.

Dr. Mamesaya reports personal fees from AstraZeneca KK, Pfizer Japan, Inc.; personal fees from Chugai Pharmaceutical Co., Ltd.; grants and personal fees from Boehringer Ingelheim; personal fees from MSD K.K.; personal fees from TAIHO PHARMACEUTICAL CO., LTD.; and personal fees from ONO PHARMACEUTICAL CO., LTD., outside the submitted work.

Dr. Kobayashi reports personal fees from Eli Lilly K.K, personal fees from Taiho Pharmaceutical, personal fees from AstraZeneca, outside the submitted work.

Dr. Omori reports personal fees from Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical, AstraZeneca K.K., Boehringer Ingelheim, Taiho Pharmaceutical, and MSD, which are unrelated to the submitted work.

Dr. Wakuda reports grants and personal fees from Chugai Pharmaceutical Co., Ltd.; personal fees from Taiho Pharmaceutical; personal fees from Boehringer Ingelheim; personal fees from Eli Lilly K.K.; personal fees from Ono Pharmaceutical, personal fees from MSD; grants from Novartis; grants from Abbvie; and grants and personal fees from AstraZeneca, outside the submitted work.

Dr. Ono reports grants from Taiho Pharmaceutical, grants from Ono Pharmaceutical, grants from Chugai Pharmaceutical Co., Ltd., and grants from Novartis Pharma K.K., outside the submitted work.

Dr. Kenmotsu reports grants and personal fees from Chugai Pharmaceutical Co, Ltd.; personal fees from Ono Pharmaceutical Co, Ltd.; personal fees from Boeringer Ingelheim; personal fees from Eli Lilly K.K; personal fees from Kyowa Hakko Kirin Co., Ltd.; personal fees from Bristol-Myers Squibb; personal fees from MSD; grants and personal fees from Novartis Pharma K.K.; grants and personal fees from Daiichi-Sankyo Co., Ltd.; grants and personal fees from AstraZeneca K.K.; personal fees from Pfizer; and personal fees from Taiho Pharma, outside the submitted work.

Dr. Murakami reports personal fees from AstraZeneca K.K., Ono Pharmaceutical, Bristol-Myers Squibb Japan, Chugai Pharmaceutical Co., Ltd., Pfizer Inc., Novartis Pharma K.K., Boehringer Ingelheim, Taiho Pharmaceutical, Eli Lilly K.K., and MSD, which are unrelated to the submitted work.

Dr. Harada reports personal fees from Daiichi Sankyo Pharmaceutical Co. during the conduct of the study as well as personal fees from Daiichi Sankyo Pharmaceutical Co., AstraZeneca K.K., Brain Labo Co., and Chugai Pharmaceutical Co. and grants from the Japan Agency for Medical Research and Development and the National Cancer Center Research and Development Fund, which are unrelated to the submitted work.

Dr. Kazuhisa Takahashi reports grants and personal fees from AstraZeneca K.K., Pfizer Japan, Inc., Eli Lilly K.K., MSD, and Boehringer Ingelheim as well as grants from Takeda Pharmaceutical Company Ltd., Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., KYORIN Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., GlaxoSmithKline Consumer Healthcare Japan K.K., SHIONOGI & CO., LTD., and Novartis Pharma K.K., which are unrelated to the submitted work.

Dr. Toshiaki Takahashi reports grants and personal fees from AstraZeneca KK, Pfizer Japan, Inc.; grants and personal fees from Eli Lilly Japan K.K.; grants and personal fees from Chugai Pharmaceutical Co., Ltd.; grants and personal fees from Ono Pharmaceutical Co., Ltd.; grants and personal fees from MSD K.K.; grants and personal fees from Boehringer Ingelheim Japan, Inc.; grants and personal fees from Pfizer Japan, Inc.; and personal fees from Roche Diagnostics K.K., outside the submitted work.

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Miyawaki, T., Naito, T., Yabe, M. et al. Impact of weight loss on treatment with PD-1/PD-L1 inhibitors plus chemotherapy in advanced non-small-cell lung cancer. Support Care Cancer 30, 1633–1641 (2022). https://doi.org/10.1007/s00520-021-06572-4

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