International journal of clinical oncology
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Int. J. Clin. Oncol. · May 2020
ReviewCombination therapy with PD-1 or PD-L1 inhibitors for cancer.
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. ⋯ 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.