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Combination therapy with PD-1 or PD-L1 inhibitors for cancer

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Abstract

Immune checkpoint inhibitors (ICIs)—such as antibodies to programmed cell death–1 (PD-1), to its ligand PD-L1, or to cytotoxic T lymphocyte-associated protein–4 (CTLA-4)—are an evolving treatment option for several types of cancer, but only a limited number of patients benefit from such therapy. Preclinical studies have suggested that the combination of PD-1 or PD-L1 inhibitors with either cytotoxic chemotherapy or antibodies to CTLA-4 is a promising treatment strategy for advanced cancer. Indeed, combinations of cytotoxic chemotherapy and PD-1/PD-L1 inhibitors have been approved and are now used in clinical practice for the treatment of advanced non-small cell lung cancer and small cell lung cancer on the basis of positive results of large-scale clinical trials. In addition, the combination of antibodies to CTLA-4 (ipilimumab) and to PD-1 (nivolumab) has been found to confer a survival benefit in patients with melanoma or renal cell carcinoma. Several ongoing clinical trials are also investigating ICI combination therapy in comparison with standard therapy for other tumor types. The identification of patients likely to achieve a sufficient benefit from PD-1/PD-L1 inhibitor monotherapy remains a challenge; however, with the establishment of novel complementary biomarkers being needed. Preclinical and clinical investigations of immune-related adverse events of ICI combination therapy are also warranted to establish management strategies. In this review, we summarize the current landscape of combination therapy with PD-1/PD-L1 inhibitors plus either cytotoxic chemotherapy or CTLA-4 inhibitors to clarify the benefits of and outstanding clinical issues related to such treatment.

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  1. Department of Medical Oncology, Faculty of Medicine, Kindai University, 377-2 Ohno-higashi, Osaka-Sayama, Osaka, 589-8511, Japan

    Hidetoshi Hayashi & Kazuhiko Nakagawa

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H. Hayashi has received honoraria from AstraZeneca K.K., Boehringer Ingelheim Japan Inc., Bristol-Myers Squibb Co. Ltd., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K., MSD K.K., Ono Pharmaceutical Co. Ltd., Pfizer Japan Inc., and Taiho Pharmaceutical Co. Ltd. as well as research funding from AbbVie Inc., AC MEDICAL Inc., Astellas Pharma Inc., AstraZeneca K.K., Boehringer Ingelheim Japan Inc., Bristol-Myers Squibb Co. Ltd., Daiichi Sankyo Co. Ltd., Eisai Co. Ltd., Eli Lilly Japan K.K., EPS Associates Co. Ltd., GlaxoSmithKline K.K., Japan Clinical Research Operations Co. Ltd., Kyowa Hakko Kirin Co. Ltd., Merck Serono Co. Ltd., MSD K.K., Novartis Pharma K.K., Ono Pharmaceutical Co. Ltd., Otsuka Pharmaceutical Co. Ltd., PAREXEL International Corp., Pfizer Japan Inc., PPD-SNBL K.K., Quintiles Transnational Japan K.K., Taiho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., and Yakult Honsha Co. Ltd. Y. Nakagawa has received honoraria from Astellas Pharma Inc., AstraZeneca K.K., Boehringer Ingelheim Japan Inc., Bristol-Myers Squibb Co. Ltd., Chugai Pharmaceutical Co. Ltd., Clinical Trial Co. Ltd., Eli Lilly Japan K.K., MSD K.K., Nichi-Iko Pharmaceutical Co. Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co. Ltd., Pfizer Japan Inc., Reno. Medical K.K., and Sym Bio Pharmaceuticals Ltd.; research funding from A2 Healthcare Corp., AbbVie Inc., Astellas Pharma Inc., Boehringer Ingelheim Japan Inc., Bristol-Myers Squibb Co. Ltd., Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Eisai Co. Ltd., Eli Lilly Japan K.K., EP-CRSU Co. Ltd., GRITSTONE ONCOLOGY Inc., ICON Japan K.K., inVentiv Health Japan, MSD K.K., Linical Co. Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co. Ltd., PAREXEL International Corp., Pfizer Japan Inc., Quintiles, Taiho Pharmaceutical Co. Ltd., and Takeda Pharmaceutical Co. Ltd.; and consulting or advisory fees from Astellas Pharma Inc., Ono Pharmaceutical Co. Ltd., and Takeda Pharmaceutical Co. Ltd.

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Hayashi, H., Nakagawa, K. Combination therapy with PD-1 or PD-L1 inhibitors for cancer. Int J Clin Oncol 25, 818–830 (2020). https://doi.org/10.1007/s10147-019-01548-1

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