Clinically approved combination immunotherapy: Current status, limitations, and future perspective.

Lu, Ligong

Zhan, Meixiao

Li, Xian-Yang

Zhang, Hui

Dauphars, Danielle J

Jiang, Jun

Yin, Hua

Li, Shi-You

Luo, Sheng

Li, Yong

He, You-Wen

2022-06-18T19:38:59Z

2022-06-18T19:38:59Z

2022-01

2022-06-18T19:38:58Z

Immune-checkpoint inhibitor-based combination immunotherapy has become a first-line treatment for several major types of cancer including hepatocellular carcinoma (HCC), renal cell carcinoma, lung cancer, cervical cancer, and gastric cancer. Combination immunotherapy counters several immunosuppressive elements in the tumor microenvironment and activates multiple steps of the cancer-immunity cycle. The anti-PD-L1 antibody, atezolizumab, plus the anti-vascular endothelial growth factor antibody, bevacizumab, represents a promising class of combination immunotherapy. This combination has produced unprecedented clinical efficacy in unresectable HCC and become a landmark in HCC therapy. Advanced HCC patients treated with atezolizumab plus bevacizumab demonstrated impressive improvements in multiple clinical endpoints including overall survival, progress-free survival, objective response rate, and patient-reported quality of life when compared to current first-line treatment with sorafenib. However, atezolizumab plus bevacizumab first-line therapy has limitations. First, cancer patients falling into the criteria for the combination therapy may need to be further selected to reap benefits while avoiding some potential pitfalls. Second, the treatment regimen of atezolizumab plus bevacizumab at a fixed dose may require adjustment for optimal normalization of the tumor microenvironment to obtain maximum efficacy and reduce adverse events. Third, utilization of predictive biomarkers is urgently needed to guide the entire treatment process. Here we review the current status of clinically approved combination immunotherapies and the underlying immune mechanisms. We further provide a perspective analysis of the limitations for combination immunotherapies and potential approaches to overcome the limitations.

S2590-2555(22)00008-7

2590-2555

2590-2555

https://hdl.handle.net/10161/25385

eng

Elsevier BV

Current research in immunology

10.1016/j.crimmu.2022.05.003

Atezolizumab

Bevacizumab

Biomarker

Combination immunotherapy

Dose

First-line therapy

Gene signature

HCC

Patient selection

Clinically approved combination immunotherapy: Current status, limitations, and future perspective.

Journal article

Luo, Sheng|0000-0003-4214-5809

He, You-Wen|0000-0002-8983-2684

118

127

Duke

School of Medicine

Basic Science Departments

Institutes and Centers

Biostatistics & Bioinformatics

Duke Clinical Research Institute

Published

3