Immune checkpoint inhibitors and chemotherapy versus chemotherapy for early triple-negative breast cancer

Gao, Ya, Liu, Ming, Li, Lun, Zhang, Junhua, Song, Fujian and Tian, Jinhui (2026) Immune checkpoint inhibitors and chemotherapy versus chemotherapy for early triple-negative breast cancer. Cochrane Database of Systematic Reviews, 2. ISSN 1361-6137

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Abstract

BACKGROUND: Triple-negative breast cancer (TNBC), an aggressive subtype lacking oestrogen and progesterone receptors and amplification of HER2 receptors, accounts for 12% to 17% of breast cancers. Adjuvant and neoadjuvant chemotherapy improve survival; however, 30% to 40% of early-stage TNBC cases progress to metastatic disease. Recent evidence suggests that combining immune checkpoint inhibitors (PD-1/PD-L1 inhibitors) with chemotherapy may improve pathological complete response and event-free survival.  OBJECTIVES: To assess the benefits and harms of immune checkpoint inhibitors (PD-1 or PD-L1 inhibitors) plus chemotherapy compared with chemotherapy for people with early TNBC.  SEARCH METHODS: We searched the Cochrane Breast Cancer Group Specialised Register, CENTRAL, MEDLINE, Embase, the WHO ICTRP, and ClinicalTrials.gov up to 6 November 2024. We also searched the reference lists of identified relevant trials or reviews for potentially eligible studies.  SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing PD-1 or PD-L1 inhibitors plus chemotherapy with chemotherapy alone in participants with early TNBC.  DATA COLLECTION AND ANALYSIS: Pairs of review authors independently identified studies for inclusion and performed data extraction and risk of bias assessment. Outcomes were pathological complete response, event-free survival (EFS), overall survival (OS), health-related quality of life (HRQoL), and overall rates of any adverse events and serious adverse events (SAEs). We calculated hazard ratios (HRs) for time-to-event data, risk ratios (RRs), odds ratios (ORs), or risk differences (RDs) for dichotomous outcomes, and mean differences (MDs) for continuous outcomes with corresponding 95% confidence intervals (CIs). We performed random-effects meta-analyses to summarise the evidence and evaluated the certainty of evidence using the GRADE approach.  MAIN RESULTS: We included seven RCTs with a total of 4341 participants. Two trials investigated PD-1 inhibitors (i.e. pembrolizumab), and five investigated PD-L1 inhibitors (i.e. durvalumab, atezolizumab) in the intervention group. Six studies used neoadjuvant chemotherapy (NACT), and one study used adjuvant chemotherapy (ACT) in the control group. The studies cover a five-year follow-up period. Two studies were at low risk of bias for all reported outcomes. The main limitation of the other trials was lack of blinding. PD-1 or PD-L1 inhibitors plus chemotherapy versus chemotherapy alone beforebreast cancer surgery PD-1 or PD-L1 inhibitors plus chemotherapy probably increase pathological complete response rate (RR 1.47, 95% CI 1.15 to 1.86; 6 studies, 1564 participants; moderate-certainty evidence); improve EFS (HR 0.64, 95% CI 0.52 to 0.79; 4 studies, 1789 participants; high-certainty evidence); and probably improve OS (HR 0.56, 95% CI 0.34 to 0.93; 3 studies, 1681 participants; moderate-certainty evidence) compared with chemotherapy alone. There may be little or no difference between PD-1 or PD-L1 inhibitors plus chemotherapy and chemotherapy alone in HRQoL (MD -1.49, 95% CI -3.88 to 0.91; 2 studies, 1395 participants; low-certainty evidence). PD-1 or PD-L1 inhibitors plus chemotherapy probably have little or no effect on any adverse events (OR 0.26, 95% CI 0.05 to 1.24; 3 studies, 1781 participants; moderate-certainty evidence) and treatment-related deaths (RD 0.2%, 95% CI -0.4% to 0.8%; 4 studies, 1761 participants; moderate-certainty evidence) compared with chemotherapy alone. PD-1 or PD-L1 inhibitors plus chemotherapy probably increase immune-related SAEs (OR 1.75, 95% CI 1.15 to 2.67; 5 studies, 2016 participants; moderate-certainty evidence) compared with chemotherapy alone. PD-1 or PD-L1 inhibitors plus chemotherapy versus chemotherapy alone afterbreast cancer surgery There may be little or no difference between PD-1 or PD-L1 inhibitors plus chemotherapy and chemotherapy alone in EFS (HR 1.11, 95% CI 0.87 to 1.42; 1 study, 2199 participants; low-certainty evidence), OS (HR 1.23, 95% CI 0.87 to 1.73; 1 study, 2199 participants; low-certainty evidence), HRQoL (MD -1.02, 95% CI -2.71 to 0.67; 1 study, 2168 participants; low-certainty evidence), any adverse events (OR 3.38, 95% CI 0.93 to 12.33; 1 study, 2177 participants; low-certainty evidence), and treatment-related deaths (RD -0.1%, 95% CI -0.4% to 0.2%; 1 study, 2177 participants; low-certainty evidence). PD-1 or PD-L1 inhibitors plus chemotherapy probably increase immune-related SAEs (OR 1.81, 95% CI 1.47 to 2.24; 1 study, 2177 participants; moderate-certainty evidence) compared to chemotherapy alone.  AUTHORS' CONCLUSIONS: Combining PD-1 or PD-L1 inhibitors with chemotherapy compared to chemotherapy alone before breast cancer surgery improves pathological response, EFS, and OS in early TNBC. In contrast, the combination of PD-1/PD-L1 inhibitors with chemotherapy after breast cancer surgery may have little to no effect on EFS and OS in early-stage TNBC when compared with chemotherapy alone. The addition of PD-1 or PD-L1 inhibitors probably increases immune-related SAEs.

Item Type:	Article
Uncontrolled Keywords:	sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Centres > Public Health
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	26 Feb 2026 12:30
Last Modified:	26 Feb 2026 12:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/102079
DOI:	10.1002/14651858.CD015072.pub2

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