Evaluation of short-course durvalumab combined with dose-dense EC in the neoadjuvant setting for locally advanced luminal B/HER2(-) or triple-negative breast cancer

Background Combining immune checkpoint inhibitors (ICI) with neoadjuvant chemotherapy (NACT) has been the standard of care for stage II and III triple negative breast cancer (TNBC) since 2021. For Luminal B/HER2(-) breast cancers (BC) recent results from randomized phase 3 clinical trials demonstrated an improvement in pathological complete response (pCR) when ICI are combined with overall NACT. Emerging real-life data on TNBC reveal rates of ICI-related toxicities higher than expected, raising questions about the possibility of reducing ICI exposure during NACT while maintaining an efficacy advantage. The B-IMMUNE study explored the safety and efficacy of short-course durvalumab combined with EC during NACT in locally advanced BC. Patients and methods The prospective phase 1b/2 trial included patients with locally advanced Luminal B/HER2(-) or TNBC who were treated with paclitaxel 80mg/m2 weekly from weeks 1–12, followed by 4 cycles of dose-dense epirubicin 90mg/m2 and cyclophosphamide 600mg/m2 biweekly (ECdd), in a neoadjuvant setting. Phase 1b evaluated a single infusion of durvalumab 1500mg combined with the 3rd cycle of ECdd and phase 2 evaluated two infusions with the 1st and 3rd cycles of ECdd respectively. The primary endpoints were safety and pathological complete response (pCR) rate versus historical control. Based on Simon’s two-stage design, the trial was considered positive if > 8/20 pCRs were observed among TNBC patients and > 5/22 for luminal B HER2(-) BC patients. Results Fifty patients were considered for safety analyses and 34% of them experienced grade 3–4 adverse events (AEs) and 8% immunity-related AEs. Of the 47 patients treated with durvalumab in phase 2, 46 (22 TNBC and 24 Luminal B/HER2(-) BC) were considered for efficacy analyses. A pCR was observed in 12/22 TNBC patients (55%) and 8/24 Luminal B/HER2(-) BC patients (33%). Conclusions The B-IMMUNE study achieved its primary objective by showing that the addition of only 2 doses of durvalumab to NACT seems to improve the pCR rate compared to a historical control without ICI, for both TNBC and Luminal B/HER2(-) BC, while maintaining an acceptable safety profile. De-escalation of ICI in the neoadjuvant setting should be further investigated in phase 3 trials. Trial registration EudraCT: 2016–003998-1 date: 19 January 2017.