271P Eribulin (E) plus endocrine therapy (ET) in patients (pts) with HR[+]/HER2[-] metastatic breast cancer (mBC) after progression on previous ET: The REVERT study

Abstract

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. 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. 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. 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.