Abstract 271P
Background
Most pts with luminal mBC progress to ET +/- targeted therapy. E treatment promotes intrinsic subtype changes in the neoadjuvant setting, shifting luminal B to luminal A tumors. REVERT (NCT03795012) explores if E increases hormonal sensitivity in aromatase inhibitor (AI)-pretreated luminal mBC pts.
Methods
REVERT is a multicenter, randomized, non-comparative phase II trial in which pts with AI-resistant, HR[+]/HER2[-], mBC were randomized (1:1) to receive E (1.23 mg/m2 on days 1 and 8 of every 21-day cycle) or E plus AI. Pts were stratified by previous CDK4/6 inhibitors. Pts must have received at least one anthracycline- and/or taxane-based regimen in the (neo)adjuvant setting and up to 3 prior lines of ET in the metastatic setting. Previous chemotherapy for mBC was not allowed. The primary endpoint was the overall response rate (ORR) as per RECIST v. 1.1 in E+AI arm. Secondary endpoints included ORR in E pts and progression-free survival (PFS) and safety as per the NCI-CTCAE v.4.0.3 in both arms. The target sample size was 60 pts. An interim analysis was planned with 22 recruited pts based on two-stage Simon design.
Results
Between June, 2019 and January, 2021, a total of 22 pts from 7 centers in Spain were enrolled. Median age was 63.0 (range 50-77) years, 21 (95.5%) pts had visceral disease and 8 (36.4%) pts presented ≥3 metastatic sites. The trial was terminated early on March 31, 2021 with 8 pts (36.4%) remained on treatment. ORR was achieved in 4 (26.7%; 95% CI: 7.8 to 55.1) of 15 pts in E+AI arm and 2 (28.6%; 95% CI: 3.7 to 71.0) of 7 pts in E arm (p=1). Median PFS was 6.3 months(mo) with E+AI and 6 mo with E alone (HR: 1.1; 95% CI, 0.3 to 3.9; p=0.932). A significant interaction (p=0.1) between treatment arm and pts with previous CDK4/6 inhibitor (HR= 0.3 favors E+AI) or without previous CDK4/6 inhibitor (HR = 3.2 favors E) was observed. All grade and grade ≥3 adverse events were similar in both arms, being neutropenia and fatigue the most frequent.
Conclusions
Although superiority of E+AI over E single therapy seems unlikely in this scenario, E+AI combination deserves further investigation in pts with ET-resistant, HR[+]/HER2[-] mBC, after progression to CDK4/6 inhibitors.
Clinical trial identification
NCT03795012.
Editorial acknowledgement
Legal entity responsible for the study
MEDSIR.
Funding
EISAI.
Disclosure
A. Lopez Gonzalez: Financial Interests, Institutional, Invited Speaker: Novartis, Pfizer; Financial Interests, Institutional, Advisory Board: Seagen. A. Cortes Salgado: Financial Interests, Personal, Advisory Board: Clovis Oncology, GlaxoSmithKline, Pfizer; Financial Interests, Personal, Speaker’s Bureau: GlaxoSmithKline, AstraZeneca Spain, MSD, Novartis; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Personal, Other: Daiichi Sankyo/AstraZeneca, ONCARE MADRID Founder. A. García, P. Gener, L. Mina, D. Alcalá: Other, Personal, Full or part-time Employment: MEDSIR. M. Sampayo-Cordero: Financial Interests, Personal, Other: MEDSIR, Syntax for Science, Nestle; Financial Interests, Personal, Advisory Board: MEDSIR, Syntax for Science, Nestle; Financial Interests, Personal, Speaker’s Bureau: MEDSIR, Syntax for Science, Nestle, Roche; Financial Interests, Personal, Funding: Syntax for Science, Nestle, Roche. J. Cortés: Financial Interests, Personal, Advisory Board: Roche, Celgene, Cellestia, Astrazeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Merck Sharp& Dohme, GSK, LEUKO, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp& Dohme, Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares: MedSIR, Nektar Therapeutics; Financial Interests, Institutional, Research Grant: Roche, Ariad Pharmaceuticals, Astrazeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma B, Queen Mary University of London; Other, Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo. J.M. Perez Garcia: Financial Interests, Personal, Advisory Board: Lilly, Roche, Eisai, Daichii Sankyo, AstraZeneca, Seattle Genetics; Financial Interests, Personal, Expert Testimony: Esai. A. Llombart Cussac: Financial Interests, Personal, Leadership Role: Eisai, Celgene, Lilly, Pfizer, Roche, Novartis, MSD; Financial Interests, Personal, Stocks/Shares: MEDSIR, Initia-Research; Financial Interests, Personal, Advisory Board: Lilly, Roche, Pfizer, Novartis, Pierre-Fabre, Genomic Health, GSK; Financial Interests, Personal, Speaker’s Bureau: Lilly, AstraZeneca, MSD; Financial Interests, Personal, Funding: Roche, Foundation Medicine, Pierre Fabre, Agendia;; Financial Interests, Personal, Other: Roche, Lilly, Novartis, Pfizer, AstraZeneca. All other authors have declared no conflicts of interest.