PD-1/PD-L1 Based Combinational Cancer Therapy: Icing on the Cake.

Jian-Ye Zhang,Jia-Jun Li,Li-Wu Fu,Rameshwar Adhikari,Yan-Yan Yan

doi:10.3389/fphar.2020.00722

Abstract

Cancer has been a major global health problem due to its high morbidity and mortality. While many chemotherapy agents have been studied and applied in clinical trials or in clinic, their application is limited due to its toxic side effects and poor tolerability. Monoclonal antibodies specific to the PD-1 and PD-L1 immune checkpoints have been approved for the treatment of various tumors. However, the application of PD-1/PD-L1 inhibitors remains suboptimal and thus another strategy comes in to our sight involving the combination of checkpoint inhibitors with other agents, enhancing the therapeutic efficacy. Various novel promising approaches are now in clinical trials, just as icing on the cake. This review summarizes relevant investigations on combinatorial therapeutics based on PD-1/PD-L1 inhibition.

Highlights

Cancer has become one of the major problems threatening human health based on its high rates of morbidity and mortality (Huang and Fu, 2015; Zhang et al, 2016; Zhang et al, 2017; Huang et al, 2020)
This study indicated that pembrolizumab demonstrated antitumor activity and was well tolerated as monotherapy and in combination with chemotherapy in patients with previously untreated advanced gastric/gastroesophageal junction adenocarcinoma (Bang et al, 2019)
In the phase Ib clinical trial NCT01633970, patients diagnosed with triple-negative breast cancer received atezolizumab (800 mg at 2-week intervals) plus nab-paclitaxel (125 mg/m2, once a week for 3 weeks in a 4-week treatment course), and five patients were evaluated for efficacy at three-month follow up (Markham, 2016; Liu et al, 2018)

Summary

Introduction

Cancer has become one of the major problems threatening human health based on its high rates of morbidity and mortality (Huang and Fu, 2015; Zhang et al, 2016; Zhang et al, 2017; Huang et al, 2020). In the two open-label, non-comparative, randomized, phase 2 trials (NCT02500797), the activity and safety of nivolumab alone or in combination with ipilimumab in patients with locally advanced, unresectable, or metastatic sarcoma were investigated.

Results

Conclusion