Neoadjuvant Abemaciclib plus Letrozole vs. Chemotherapy in patients with HR+/HER2- Highly Proliferative Breast Cancer.

Autores de IIS La Fe

• Ana Santaballa Bertrán

  Autor

Participantes ajenos a IIS La Fe

• Martín, M
• Guerrero-Zotano, AL
• Pérez-López, ME
• Ruiz-Borrego, M
• Martinez Janez, Noelia
• Chacón, JI
• Gil-Gil, M
• Andrés, R
• Bermejo, B
• Sánchez-Rovira, P
• Del Barco, S
• Ponce, JJ
• Fernández, I
• Martinez de Duenas, Eduardo
• Hinojo-González, C
• González, M
• García-Garre, E
• Hernando, B
• de la Haba-Rodriguez, J
• Alvarez, IM
• González-Santiago, S
• García-Sáenz, JA
• Casas, M
• Bezares, S
• Caballero, R
• Rojo, F
• Alba, E

Grupos

• Grupo de Investigación en tumores ginecológicos, cáncer de mama y cáncer hereditario

Abstract

PURPOSE: Neoadjuvant chemotherapy is standard for high-risk HR+/HER2-breast cancer (BC). 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 HR+/HER2- stage II-III BC patients with Ki-67 =20% to receive letrozole/abemaciclib for 12 months or chemotherapy for 6 months. Patients were stratified by menopausal status, TNM stage, and Ki-67 index (<30% vs. =30%). The primary endpoint was the rate of residual cancer burden (RCB) 0-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: 200 patients (median age 53 years, 57% postmenopausal, 79% stage II, 77% Ki-67 =30%, 58% RS =26) were randomized. RCB 0-I was achieved in 13% (letrozole/abemaciclib, 95% Credible Intervals (CrI): 7.4% - 20.5%) vs. 18% (chemotherapy, 95% CrI: 11.5% - 26.4%), failing to show similarity between treatment arms. The CRRs were 78% (letrozole/abemaciclib) vs. 71% (chemotherapy) (P=0.26). Tumors with Ki-67 =30% and/or RS results =26 showed a trend toward higher RCB 0-I rates with chemotherapy (23% vs. 17%, P=0.52). RCB 0-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-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.

Keywords

• Adult; Aged; Aminopyridines; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Breast Neoplasms; Erb-b2 Receptor Tyrosine Kinases; Female; Humans; Ki-67 Antigen; Letrozole; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Receptors, Estrogen; Receptors, Progesterone; Treatment Outcome; abemaciclib; aminopyridine derivative; antineoplastic agent; benzimidazole derivative; epidermal growth factor receptor 2; ERBB2 protein, human; estrogen receptor; Ki 67 antigen; letrozole; progesterone receptor; adult; aged; breast tumor; cancer staging; clinical trial; controlled study; drug therapy; female; genetics; human; metabolism; middle aged; multicenter study; neoadjuvant therapy; pathology; phase 2 clinical trial; procedures; randomized controlled trial; treatment outcome