112MO Neoadjuvant study of 12 months of abemaciclib plus letrozole vs chemotherapy in HR+/HER2– highly proliferative (Ki67≥20%) breast cancer: CARABELA (GEICAM/2019-01) trial

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Both chemotherapy (CT) and endocrine therapy + abemaciclib (ET/ABE) are recommended for high-risk HR+/HER2 early breast cancer (EBC). It is unclear if 12 months (mo.) of ET/ABE could replace CT. We investigate this by comparing their efficacy in neoadyuvant (NAT) setting. CARABELA (NCT04293393) is a phase II, randomized, open-label, study comparing 12 mo. of ET (letrozole +LHRH analogs in premenopausal patients +ABE) vs. 6 mo. of CT (standar anthracyclines plus taxanes regimens) as NAT of HR+/HER2−, Ki67 ≥20% and stage II-III BC. Stratification included TNM, menopausal status, and Ki67 (<30% vs. ≥30%). Primary endpoint: rate of residual cancer burden (RCB) 0-I, for patients (pts.) whose disease requiring additional NAT, RCBIII was assigned. Secondary endpoints: RCB class distribution, PEPI score 0, clinical response rate (CRR), and safety. Bayesian method was used for sample size calculation, requiring >80% probability for <5% difference in RCB 0-I to confirm ET/ABE and CT similarity. Recruited 100 pts./arm at 24 Spanish sites. Median age was 53; with 57% postmenopausal; 79% stage II; 61% N1-2; 77% Ki67 ≥30%. In the ET/ABE arm, 79% of pts completed 12 mo. of treatment. RCB assessed in 95% of pts. RCBIII was assigned to 7 pts of the ET/ABE arm who were receiving other NAT prior surgical resection. ET/ABE did not show similar RCB 0-I rate compared to CT (13% vs. 18%) (Table). CRR showed no significant difference between ET/ABE (78%) and CT (71%) (P=0.26). PEPI score 0 was 14% for ET/ABE and 26% for CT (P=0.03). Treatment discontinuation by AEs was ET/ABE 9% vs. CT 4%.Table: 112MOET/ABE (±LHRH analogs)CTN=100N=100RCB 0-I (%)Posterior median131895% Credible Interval7 – 2112 – 26Posterior probability of <5% difference51RCB CLASS DISTRIBUTION (%)0410I98II5756III2223Not Assessable83P-value (0-I vs II vs III)0.70RCB SCOREMean (SD)2.52 (1.05)2.15 (1.16)P-value0.04 Open table in a new tab CARABELA study did not achieve its primary endpoint, as 12 mo. of preoperative ET/ABE did not show a similar RCB 0-I rate to CT in highly proliferative HR+/HER2− BC pts. However, ET/ABE showed similar RCB class distribution and CRR compared to CT.