Immune Checkpoint Inhibitors Combined with Targeted Therapy: The Recent Advances and Future Potentials

Author:

Li Bin12,Jin Juan12,Guo Duancheng1,Tao Zhonghua12,Hu Xichun12ORCID

Affiliation:

1. Department of Breast and Urologic Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China

2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized the therapeutic landscape of cancer and have been widely approved for use in the treatment of diverse solid tumors. Targeted therapy has been an essential part of cancer treatment for decades, and in most cases, a special drug target is required. Numerous studies have confirmed the synergistic effect of combining ICIs with targeted therapy. For example, triple therapy of PD-L1 inhibitor atezolizumab plus BRAF inhibitor vemurafenib and MEK inhibitor cobimetinib has been approved as the first-line treatment in advanced melanoma patients with BRAFV600 mutations. However, not all combinations of ICIs and targeted therapy work. Combining ICIs with EGFR inhibitors in non-small-cell lung cancer (NSCLC) with EGFR mutations only triggered toxicities and did not improve efficacy. Therefore, the efficacies of combinations of ICIs and different targeted agents are distinct. This review firstly and comprehensively covered the current status of studies on the combination of ICIs mainly referring to PD-1 and PD-L1 inhibitors and targeted drugs, including angiogenesis inhibitors, EGFR/HER2 inhibitors, PARP inhibitors and MAPK/ERK signaling pathway inhibitors, in the treatment of solid tumors. We discussed the underlying mechanisms, clinical efficacies, side effects, and potential predictive biomarkers to give an integrated view of the combination strategy and provide perspectives for future directions in solid tumors.

Funder

National Natural Science Foundation of China

National Science and Technology Major Project

Clinical Research Plan of Shanghai Hospital Development Center

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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