Net clinical value of neoadjuvant immune checkpoint inhibitors in early triple-negative breast cancer: Integrating efficacy heterogeneity and treatment burden.

Le résumé fourni par la source

e12659 Background: Neoadjuvant immune checkpoint inhibitors (ICIs) improve pathological complete response (pCR) rates in early-stage triple-negative breast cancer (TNBC). In curative-intent settings, however, treatment escalation should be guided not only by efficacy signals but also by baseline clinical risk and downstream treatment burden. Whether neoadjuvant ICIs provide a consistent net clinical value across TNBC risk groups remains uncertain. Methods: We performed a trial-level meta-analysis of randomized phase II–III trials comparing neoadjuvant chemotherapy with or without ICIs in early TNBC. Odds ratios (ORs) for pCR and hazard ratios (HRs) for event-free survival (EFS) were pooled using inverse-variance models. Prespecified subgroup analyses were conducted according to nodal status and tumor stage to explore efficacy heterogeneity. To contextualize efficacy findings in a curative-intent setting, treatment discontinuation due to adverse events was evaluated as a competing clinical consideration, estimating absolute excess risk and numbers needed to harm (NNH). Results: Over 3,000 patients with early TNBC were included. ICIs significantly increased pCR rates, with marked heterogeneity across clinical risk groups. The pCR benefit was pronounced in node-positive disease (OR 2.57, 95% CI 1.76–3.75) but attenuated and not statistically significant in node-negative patients (OR 1.29, 95% CI 0.93–1.80). By contrast, EFS benefit was observed across risk categories, including both node-positive (HR 0.63, 95% CI 0.47–0.86) and node-negative disease (HR 0.65, 95% CI 0.46–0.93), highlighting a discordance between early response endpoints and long-term outcomes in lower-risk patients. Across trials, ICI-containing regimens were associated with clinically relevant excess treatment discontinuation due to adverse events, with absolute increases ranging from 3% to 11%, corresponding to one additional treatment discontinuation for every 9–36 patients treated. Conclusions: In early TNBC, neoadjuvant ICIs do not deliver uniform net clinical value across patient subgroups. While long-term outcome improvements extend across risk categories, heterogeneous early efficacy gains combined with non-negligible treatment discontinuation challenge universal escalation strategies, particularly in lower-risk disease. Integrating long-term benefit with treatment burden is essential to define the true clinical value of neoadjuvant immunotherapy and to support a risk-adapted, value-oriented approach rather than routine intensification.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.