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
Abstract
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. 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. 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. 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. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420261356428 , identifier CRD420261356428.