Neoadjuvant Abemaciclib plus Letrozole Versus Chemotherapy in Patients with HR+/HER2− Highly Proliferative Breast Cancer
Year: 2025
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
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.
Source: Clinical Cancer Research
Authors: Miguel Martín, Ángel L. Guerrero-Zotano, María E. Pérez-López, Manuel Ruiz-Borrego, Noelia Martínez Jáñez, José I. Chacón, Miguel Gil-Gil, Raquel Andrés, Begoña Bermejo, Pedro Sánchez-Rovira, Sonia del Barco, José J. Ponce, Isaura Fernández, Eduardo Martínez de Dueñas, Carmen Hinojo-González, Marta González, Elisa García-Garre, Blanca Hernando, Juan de la Haba-Rodriguez, Isabel M. Álvarez, Santiago González-Santiago, José Á. García-Sáenz, Ana Santaballa, Maribel Casas, Susana Bezares, Rosalía Caballero, Federico Rojo, Emilio Alba
Institutions: Universidad Complutense de Madrid, Instituto de Salud Carlos III, Hospital General Universitario Gregorio Marañón, Centro de Investigación Biomédica en Red de Cáncer, GEICAM – Spanish Breast Cancer Group, Instituto de Investigación Sanitaria Gregorio Marañón, Fundación Instituto Valenciano de Oncología, Complexo Hospitalario Universitario A Coruña, Hospital Universitario Virgen del Rocío, Hospital Universitario Ramón y Cajal, Hospital Universitario de Toledo, Institut d'Investigació Biomédica de Bellvitge, Institut Català d'Oncologia, Hospital Clínico Universitario Lozano Blesa, Universitat de València, Hospital Clínico Universitario de Valencia, INCLIVA Health Research Institute, Complejo Hospitalario de Jaén, Hospital General Universitario de Alicante Doctor Balmis, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Consorcio Hospitalario Provincial de Castellón, Marqués de Valdecilla University Hospital, Instituto de Investigación Marqués de Valdecilla, Hospital General Universitario Morales Meseguer, Instituto Murciano de Investigación Biosanitaria, Hospital Universitario de Burgos, Instituto Maimónides de Investigación Biomédica de Córdoba, Hospital Universitario Reina Sofía, University of Córdoba, Biogipuzkoa Health Research Institute, Donostiako Unibertsitate Ospitalea, Hospital San Pedro de Alcántara, Complejo Hospitalario de Cáceres, Hospital Clínico San Carlos, Hospital Universitari i Politècnic La Fe, Hospital Universitario Fundación Jiménez Díaz, Hospital Clínico Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4417283922