PD-1/PD-L1 immune checkpoint inhibitors in the treatment of unresectable locally advanced or metastatic triple negative breast cancer: a meta-analysis on their efficacy and safety.

Background: Triple negative breast cancer (TNBC) represents a particularly aggressive and clinically challenging subtype of breast cancer, characterized by its invasive nature and generally poor prognosis. Treatment options for unresectable TNBC are limited. In recent years, the advent of PD-1/PD-L1 immune checkpoint inhibitors has offered a promising new treatment option for unresectable TNBC. The role of PD-1/PD-L1 immune checkpoint inhibitors (ICIs) in unresectable TNBC management remains a subject of debate. This article aims to synthesize evidence from randomized controlled trials (RCTs) through a meta-analysis (MA) to provide a comprehensive evaluation of the efficacy and safety profile of ICIs in the treatment of unresectable TNBC.

Method: We searched PubMed, Embase, Cochrane library, Web of Science, and ClinicalTrials.gov for the eligible RCTs which compared the efficacy and safety of PD-1/PD-L1 ICIs and chemotherapy alone. The outcomes analyzed included overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse effects (AEs).

Results: This meta-analysis included 11 trials. Therapy with PD-L1 inhibitors was superior to chemotherapy in terms of OS in both the intention-to-treat (ITT) population and the PD-L1-positive population. (ITT: HR: = 0.90 [0.81, 0.99], P = 0.04, I = 48%; PD-L1 + : HR = 0.82 [0.70, 0.95], P = 0.01, I = 64%); In terms of PFS, treatment with PD-L1 inhibitors prolonged PFS in both the ITT and PD-L1-positive populations compared with chemotherapy (ITT: HR: = 0.85 [0.77, 0.93], P = 0.0006, I = 46%; PD-L1 + : HR = 0.72 [0.62, 0.83], P < 0.00001, I = 70%, Fig. 5); Compared with chemotherapy alone, treatment with PD-1 inhibitors prolonged OS in both the PD-L1-positive and ITT populations. (ITT: HR = 0.87 [0.78, 0.96], P = 0.007, I = 71%; CPS ≥ 1: HR = 0.81 [0.71, 0.92], P = 0.001, I = 39%); In terms of PFS, therapy with PD-1 inhibitors improved PFS in both the ITT population and the PD-L1-positive population compared with chemotherapy. (ITT: HR = 0.79 [0.70, 0.90], P = 0.0004, I = 0%; CPS ≥ 1: HR = 0.71 [0.61, 0.83], P < 0.0001, I = 0%; CPS ≥ 10: HR = 0.67 [0.53, 0.84], P = 0.0008, I = 0%).

Conclusion: Both PD-1 and PD-L1 inhibitors can offer survival benefits to TNBC patients, with the primary beneficiaries being those who are PD-L1-positive. However, immunotherapy can also lead to an increase in treatment-related adverse events. Therefore, it is essential to conduct a risk assessment for each patient before starting treatment to prevent the occurrence of serious adverse reactions.

Trial Registration: This systematic review study has been filed with PROSPERO (Registration number: CRD42024571775).