PD-1/PD-L1 inhibitors combined with chemotherapy or as monotherapy versus chemotherapy alone or observation in triple-negative breast cancer: a systematic review and updated meta-analysis incorporating long-term survival data
In brief
Immunotherapy plus chemotherapy lowers early-stage TNBC death risk by 36%
Across 10 randomized trials, adding immunotherapy to chemotherapy was associated with a 36% lower death hazard in early-stage triple-negative breast cancer, alongside better event-free survival. In metastatic disease, overall survival also favored the combination, but the adjusted estimate included no benefit; gains were greater in PD-L1-positive tumors. Chemotherapy backbone may matter, and benefit for PD-L1-negative patients remains uncertain.
- Journal
- Frontiers in immunology (Q1)
- Published
- 6 October 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Bing Guan, Yawen Chen, Rong Zhou, Sijia Zhang, Lulu Li, Ping He
- PMID
- 42903114
- DOI
- 10.3389/fimmu.2026.1958007
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (paper of the day, 23 October 2026): Meta-analysis finds survival benefit from immunotherapy in TNBC
Abstract
BACKGROUND: Multiple RCTs have established PD-1/PD-L1 inhibitors as standard in triple-negative breast cancer (TNBC), but prior meta-analyses lacked complete setting coverage, mature long-term survival data, and a quantification of chemotherapy-backbone impact-critical given IMpassion130 (nab-paclitaxel, positive) vs. IMpassion131 (paclitaxel, negative). This update includes final KEYNOTE-522 OS, GeparNuevo 7-year follow-up, and TORCHLIGHT Phase III data, covering neoadjuvant to metastatic disease. METHODS: We searched PubMed and ClinicalTrials.gov to May 2026 plus conference proceedings; an Embase search found no additional trials. Included RCTs compared ICI + chemotherapy vs. chemotherapy alone in TNBC, stratified by setting. The primary endpoints are OS (metastatic) and EFS/iDFS (early-stage). Pooled HRs used random-effects meta-analysis with HKSJ adjustment. RESULTS: A total of 10 RCTs (5,953 patients) met the inclusion. In the metastatic setting (five RCTs, n = 3,526), ICI improved OS (HR 0.85, 95% CI 0.74-0.96; HKSJ-adjusted 0.70-1.03; I² = 27%) and PFS (HR 0.82, 0.73-0.92; I² = 35%); OS benefit was greater in PD-L1+ patients (HR 0.79, 0.65-0.95; I² = 51%). Numerically greater OS with anti-PD-1 vs. anti-PD-L1 was not robust in the sensitivity analysis. In the early-stage setting (five RCTs, n = 2,427), ICIs improved EFS/iDFS (HR 0.75, 0.63-0.90; I² = 0.2%) and OS (HR 0.64, 0.53-0.78; I² = 0%) and increased pCR (OR 1.65, 1.39-1.98; I² = 1%). HKSJ adjustment widened the Cis, but the effect patterns remained consistent. CONCLUSIONS: This update confirms a consistent survival benefit of ICI + chemotherapy in both early and metastatic TNBC, which was most pronounced in PD-L1+ populations. Long-term data show durability, especially in neoadjuvant/adjuvant settings. The divergent outcomes with nab-paclitaxel vs. paclitaxel underscore the critical role of the chemotherapy backbone. These findings support current guidelines and highlight the need for refined biomarkers to extend benefit to PD-L1-negative patients. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420261356428, identifier CRD420261356428.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.