Abstract
PURPOSE: Neoadjuvant chemotherapy is standard for high-risk hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer. This study evaluates whether 12 months of letrozole plus abemaciclib could be an alternative. PATIENTS AND METHODS: The phase II, open-label CARABELA trial randomized patients with HR+/HER2- stage II to III breast cancer with Ki-67 ≥20% to receive letrozole/abemaciclib for 12 months or chemotherapy for 6 months. Patients were stratified by menopausal status, tumor-node-metastasis, and Ki-67 index (<30% vs. ≥30%). The primary endpoint was the rate of residual cancer burden (RCB) 0 to I. Secondary endpoints included clinical response rate (CRR) and correlations of Ki-67 and recurrence score (RS) with tumor response. A Bayesian design aimed to assess treatment similarity. RESULTS: A total of 200 patients (median age 53 years, 57% postmenopausal, 79% stage II, 77% Ki-67 ≥30%, 58% RS ≥26) were randomized. RCB 0 to I was achieved in 13% [letrozole/abemaciclib; 95% credible intervals (CrI), 7.4%-20.5%] versus 18% (chemotherapy; 95% CrI, 11.5%-26.4%), failing to show similarity between treatment arms. The CRR were 78% (letrozole/abemaciclib) versus 71% (chemotherapy; P = 0.26). Tumors with Ki-67 ≥30% and/or RS results ≥26 showed a trend toward higher RCB 0 to I rates with chemotherapy (23% vs. 17%; P = 0.52). RCB 0 to I rates were similar between treatments for tumors with Ki-67 <30% or RS <26. CONCLUSIONS: CARABELA trial results suggest that 12 months of letrozole/abemaciclib may not offer similar efficacy to that of chemotherapy in achieving RCB 0 to I. However, in less proliferative tumors (RS <26 or Ki-67 <30%), outcomes were comparable, suggesting that letrozole/abemaciclib could replace (neo)adjuvant chemotherapy in selected patients.