Abstract P4-07-16: B-IMMUNE final analysis: a phase Ib/II study of durvalumab combined with dose-dense EC in a neoadjuvant setting for patients with locally advanced luminal B HER2(-) or triple negative breast cancers
Authors: Devaux Alix , Beniuga Gabriela , Quaghebeur Claire , Henry Stéphanie , Van Bockstal Mieke , Galant Christine , Delrée Paul , Canon Jean-Luc , Honhon Brigitte , Korman Dominique , Verschaeve Vincent , Lonchay Christophe , Lefevre Sarah , D’Hondt Lionel , Berlière Martine , Delmarcelle Sophie , Mine Jean-Michel , Willems Timour , Müller Gebhard , Myant Nathalie , Bar Isabelle , Haussy Sandy , Coulie Pierre G. , Duhoux François P. , Carrasco Javier 
Published: March 2023

Abstract
Background: Neoadjuvant association of immune checkpoints inhibitors (ICI) and dose dense chemotherapy is promising for triple negative breast cancers (TNBC). However, response rates vary from one study to another. Timing, best chemotherapy partner and efficacy in less immunogenic breast cancer (BC), like luminal B tumors, should be further investigated. This study evaluates for TNBC and luminal B HER2(-) BC the neoadjuvant treatment with paclitaxel followed by a short combination of an anti-PD-L1 antibody with anthracyclines. Method B-IMMUNE (NCT03356860), a multicentric phase Ib/II prospective trial, included patients with stage I to III luminal B HER2(-) or TNBC treated with paclitaxel 80mg/m2 weekly from week 1 to 12 followed by 4 cycles of epirubicine 90mg/m2 and cyclophosphamide 600 mg/m2 (EC) Q2W in a neoadjuvant setting. Phase Ib evaluated a single infusion of durvalumab (anti-PD-L1) combined with the 3rd cycle of EC. Phase II evaluated infusions of durvalumab with the 1st and 3rd EC cycles. Surgery was planned 3 weeks after the last EC cycle. Primary objectives were safety and pathological complete response (pCR) rate compared to a historical control. Secondary endpoint was the overall response rate (ORR) based on breast MRI. Eleven patients were enrolled in a control arm without durvalumab, exclusively for translational research purposes. Based on a 2-stage Simon design with an α = 0.1 and β = 0.1, 22 TNBC patients were needed in the phase II to test a null hypothesis of 30% pCR rate against a one-side alternative of 60%, and 24 luminal B BC patients to test a null hypothesis of 15% pCR rate against a one-side alternative of 40% (including an additional accrual margin of 10% for eventual dropouts). At least 9 pCRs had to be observed among the first 20 evaluable TNBC patients and 6 among the first 22 evaluable luminal B patients to rule out the null hypothesis. Results This analysis concerns the 50 patients treated with the experimental treatment, 3 from the phase Ib and 47 from the phase II part. Median age was 51 y-old (31 to 72y), tumor subtypes were 24 TNBC, 25 Luminal B and one sarcoma excluded from the efficacy analysis. Seven (14%) patients had a stage I tumor, 17 (34%) a stage IIA, 13 (26%) a stage IIB, 8 (16%) a stage IIIA, 4 (8%) a stage IIIB and 1 (2%) a stage IIIC. Concerning safety, 232 AEs were reported on 39/50 patients and 34 (14,6%) were graded ≥ 3. The 5 most frequent all-grade AEs were fatigue (8,2%), diarrhea (5,6%), neutropenia (5,2%), anemia and nausea (4,3%). Most frequent grade 3 AEs were anemia and neutropenia (14,7%). Among 4 immune-related adverse events, all were thyroid disorders. One patient died 10 months after the end of treatment due to progressive disease in the liver. Forty-six of the 47 phase II patients were evaluable for efficacy. pCR was reported in 12/22 TNBC patients (55%) and 8/24 luminal B HER2(-) patients (33%). Subgroup analyses based on PD-L1 expression and TILs score are planned. Conclusions The B-IMMUNE study met its primary objective showing a significant improvement in pCR versus the historical control in both TNBC and in Luminal B HER2(-) BC cohorts with the addition of only 2 doses of durvalumab to the anthracyclines. The safety profile is comparable to those previously described with reported immune related adverse events limited to thyroid endocrine disorders.
Citation Format: Alix Devaux, Gabriela Beniuga, Claire Quaghebeur, Stéphanie Henry, Mieke Van Bockstal, Christine Galant, Paul Delrée, Jean-Luc Canon, Brigitte Honhon, Dominique Korman, Vincent Verschaeve, Christophe Lonchay, Sarah Lefevre, Lionel D’Hondt, Martine Berlière, Sophie Delmarcelle, Jean-Michel Mine, Timour Willems, Gebhard Müller, Nathalie Myant, Isabelle Bar, Sandy Haussy, Pierre G. Coulie, François P. Duhoux, Javier Carrasco. B-IMMUNE final analysis: a phase Ib/II study of durvalumab combined with dose-dense EC in a neoadjuvant setting for patients with locally advanced luminal B HER2(-) or triple negative breast cancers. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-16.