Combination regimens with PD-1/PD-L1 immune checkpoint inhibitors for gastrointestinal malignancies

Gastrointestinal (GI) malignant neoplasms have a high global incidence and treatment prospects for patients with advanced GI tumors are dismal. PD-1/PD-L1 inhibitors emerged as a frontline treatment for several types of cancer. However, the shortcomings of PD-1/PD-L1 inhibitors have been observed, including low objective response rates and acquired tumor resistance, especially in patients receiving PD-1/PD-L1 inhibitors as a single treatment. Accumulating evidence from clinical trials increasingly suggests that combined immunotherapies enhance therapeutic responses in patients with malignances, especially for GI tumors which have a complex matrix, and significant molecular and immunological differences. Preclinical and clinical studies suggest there are advantages to combined immunological regimens, which represents the next logical step in this field, although further research is necessary. This literature review explores the current limitations of monotherapies, before critically discussing the rationale behind combination regimens. Then, we provide a summary of the clinical applications for gastrointestinal cancers.