Efficacy and safety of combination PD-1/PD-L1 checkpoint inhibitors for malignant solid tumours: A systematic review

Area of Science:

• Oncology
• Immunotherapy
• Clinical Trials

Background:

• Programmed death (PD)-1/PD-L1 inhibitors are used to treat various solid tumors.
• The efficacy and safety of combining PD-1/PD-L1 inhibitors with other therapies remain under investigation.
• Controversy exists regarding the balance of benefits and immune-related adverse events in combination regimens.

Purpose of the Study:

• To evaluate the efficacy and safety of combination therapies involving PD-1/PD-L1 inhibitors in patients with malignant solid tumors.
• To conduct a meta-analysis assessing overall survival (OS), progression-free survival (PFS), and adverse events (AEs).

Main Methods:

• A systematic meta-analysis was performed using data from PubMed, Web of Science, Medline, EMBASE, and Cochrane Library up to January 2020.
• Nineteen articles were selected for analysis.
• A random-effect model was employed due to heterogeneity; hazard ratios (HR) for OS and PFS, and risk ratios (RR) for AEs were calculated.

Main Results:

• Combined PD-1/PD-L1 inhibitors significantly prolonged both OS (HR 0.72, P < 0.001) and PFS (HR 0.66, P < 0.001).
• The incidence of all-grade and severe (grade 3-5) adverse events was not significantly increased compared to control groups (HR 1.01, P = 0.31 and HR 1.10, P = 0.07, respectively).
• Subgroup analyses by tumor type, therapeutic schedule, and therapy line did not reveal significant increases in adverse events.

Conclusions:

• Combination therapy utilizing PD-1/PD-L1 inhibitors demonstrates significant clinical benefits in prolonging survival for patients with solid tumors.
• These combination therapies do not appear to significantly increase the risk of adverse events.
• The findings support the use of combined PD-1/PD-L1 inhibitors as an effective treatment strategy in oncology.