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
- 1Department of Pathology, Suzhou BenQ Medical Center
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; I ² = 27%) and PFS (HR 0.82, 0.73–0.92; I ² = 35%); OS benefit was greater in PD-L1+ patients (HR 0.79, 0.65–0.95; I ² = 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; I ² = 0.2%) and OS (HR 0.64, 0.53–0.78; I ² = 0%) and increased pCR (OR 1.65, 1.39–1.98; I ² = 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.
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BibTeX
@article{guan2026pd1pdl1,
title = {{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}},
author = {Bing Guan and Yawen Chen and Rong Zhou and Sijia Zhang and Lulu Li and Ping He},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1958007},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1958007/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Bing Guan
AU - Yawen Chen
AU - Rong Zhou
AU - Sijia Zhang
AU - Lulu Li
AU - Ping He
PY - 2026
DA - 2026/10/06
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1958007
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1958007/full
AB - 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; I ² = 27%) and PFS (HR 0.82, 0.73–0.92; I ² = 35%); OS benefit was greater in PD-L1+ patients (HR 0.79, 0.65–0.95; I ² = 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; I ² = 0.2%) and OS (HR 0.64, 0.53–0.78; I ² = 0%) and increased pCR (OR 1.65, 1.39–1.98; I ² = 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.
SN - 1664-3224
ER -