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

Background

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.

Methods

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.

Results

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: 112MO

Conclusions

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.

Clinical trial identification

NCT04293393.

Legal entity responsible for the study

GEICAM, Spanish Breast Cancer Group, Madrid, Spain.

Funding

Lilly, Exact Sciences.

Disclosure

M. Martin Jimenez: Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Roche/Genentech, Daiichi Sankyo, Menarini-Stemline; Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Lilly, Novartis, Roche/Genentech; Financial Interests, Institutional, Research Grant: Novartis, Roche, PUMA; Non-Financial Interests, Member of Board of Directors: TRIO; Non-Financial Interests, Leadership Role: GEICAM; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Affiliate: SEOM. A.L. Guerrero Zotano: Financial Interests, Personal, Advisory Role: Pfizer, AstraZeneca, Novartis, Seagen, Exact Science, Lilly, Pierre Fabre; Financial Interests, Personal, Speaker’s Bureau: Pfizer, AstraZeneca, Novartis, Seagen, Exact Science, Lilly, Pierre Fabre; Financial Interests, Personal, Other, Travel, accommodation, expenses: Pfizer, AstraZeneca, Gilead, Novartis, Pierre Fabre. N. Martinez: Financial Interests, Personal, Advisory Role: Pfizer, Roche, Lilly, Novartis, AstraZeneca/Daiichi-Sankyo; Financial Interests, Personal, Funding: Pfizer; Financial Interests, Personal, Other, Travel, accommodation, expenses: Pfizer. M.J. Gil: Financial Interests, Personal, Other, Honoraria: Pfizer, Daiichi Sankyo, Gilead; Financial Interests, Personal, Advisory Role: Seagen, Daiichi Sankyo, AstraZeneca; Financial Interests, Personal, Other, Travel, accommodation, expenses: Novartis, Roche, Pfizer. B. Bermejo: Financial Interests, Personal, Invited Speaker: Novartis, Lilly, Daiichi Sankyo, Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca, Seagen, Roche, Gilead. J.J. Ponce: Financial Interests, Personal, Advisory Board: Seattle Genetics, Novartis, AstraZeneca/Daiichi Sankyo, Roche, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, AstraZeneca/Daiichi Sankyo, Seattle Genetics, Lilly. I. Fernandez Perez: Financial Interests, Personal, Invited Speaker, training session: Merck; Financial Interests, Personal, Invited Speaker, Training session: GSK. E. Martinez de Dueñas: Financial Interests, Personal, Advisory Role: Lilly. F. Rojo: Financial Interests, Personal, Advisory Role: Roche, AstraZeneca, BMS, MSD, Merck, Novartis, Menarini, GSK, Palex, Pfizer, Daiichi Sankyo; Financial Interests, Institutional, Funding: Roche, AstraZeneca, Merck, MSD, Novartis, Pfizer; Financial Interests, Personal, Other, Travel, accommodation, expenses: Roche, AstraZeneca, BMS. E. Alba: Financial Interests, Personal, Advisory Role: Pfizer, Novartis, Roche, Lilly, BMS, Exact Sciences. All other authors have declared no conflicts of interest.