Immune checkpoint inhibitors plus chemotherapy for early-stage or locally -advanced triple-negative breast cancer: a systematic review and Bayesian network meta-analysis of randomized trials

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Abstract

BACKGROUND: Immune checkpoint inhibitors (ICIs) combined with chemotherapy have become a cornerstone in managing early and locally advanced triple-negative breast cancer (TNBC). Yet direct comparative evidence on the relative efficacy and safety of different PD-1/PD-L1 agents and treatment strategies-particularly neoadjuvant-only versus perioperative, "full-course" approaches-remains limited. To guide clinical decision-making, we performed a Bayesian network meta-analysis (NMA) comparing six specific ICI-based regimens and four overarching treatment strategies. METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Web of Science from database inception through February 25, 2026. Eligible randomized controlled trials (RCTs) enrolled patients with previously untreated early or locally advanced TNBC and compared ICI plus neoadjuvant chemotherapy with chemotherapy alone. The primary endpoint was pathological complete response (pCR); secondary endpoints included overall survival (OS) and grade ≥3 adverse events (AEs ≥3). We assessed risk of bias using the Cochrane RoB 2 tool. A Bayesian random-effects model was applied for the NMA; effects are reported as odds ratios (ORs) or hazard ratios (HRs) with 95% credible intervals (CrIs). Treatment rankings were derived from surface under the cumulative ranking curve (SUCRA) values. Certainty of evidence was evaluated using the GRADE framework, supplemented by the CINeMA tool. RESULTS: Eight RCTs involving 2,073 patients met the inclusion criteria, encompassing four strategic treatment categories and six specific ICI-containing regimens. For pCR, PD-1 (neoadjuvant) + CT (OR 2.56, 95% CrI 1.55-4.22), PD-L1 (perioperative) + CT (OR 2.00, 95% CrI 1.29-3.09), and PD-1 (perioperative) + CT (OR 1.71, 95% CrI 1.39-2.10) each significantly improved pCR rates versus chemotherapy alone, though certainty of evidence ranged from moderate to very low. PD-L1 (neoadjuvant) + CT showed a numerical trend toward higher pCR (OR 1.41, 95% CrI 0.98-2.01) without reaching statistical significance. Regarding OS, both PD-L1 (neoadjuvant) + CT (HR 0.24, 95% CrI 0.08-0.72) and PD-1 (perioperative) + CT (HR 0.63, 95% CrI 0.48-0.82) demonstrated significant survival benefits over chemotherapy. In sensitivity analyses, durvalumab (neoadjuvant) + CT and pembrolizumab (perioperative) + CT yielded identical HRs (0.24 and 0.63, respectively). Safety profiles varied: camrelizumab (perioperative) + CT (OR 0.60, 95% CrI 0.34-1.04) and pembrolizumab (neoadjuvant) + CT (OR 0.53, 95% CrI 0.28-1.01) suggested reduced risks of AEs ≥3, but these findings did not achieve statistical significance and were supported by low-to-very-low certainty evidence. CONCLUSIONS: ICI-chemotherapy combinations consistently improve pCR rates in early and locally advanced TNBC. Notably, while our analysis hints at potential survival advantages with neoadjuvant PD-L1 blockade and perioperative PD-1 inhibition, these signals derive from only three studies and remain hypothesis-generating rather than practice-changing. Future head-to-head RCTs are warranted to confirm these observations and to better define long-term safety profiles. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD420261385223.

Abstract as published, via PubMed.