LBA23 - ABIGAIL: Randomized phase II study of abemaciclib plus endocrine therapy (ET) with or without a short course of induction paclitaxel in patients (pts) with previously untreated HR-positive/HER2-negative advanced breast cancer (HR+/HER2- ABC) with aggressive disease criteria

Background

CDK4/6 inhibitor + ET represents the standard first-line therapy for HR+/HER2- ABC. However, chemotherapy (CT) as induction treatment is still used for pts at risk of rapid progression. ABIGAIL assessed the efficacy of abemaciclib + ET compared to CT followed by abemaciclib + ET in inducing early responses in HR+/HER2- ABC pts with aggressive disease features associated to poor prognosis.

Methods

ABIGAIL is an open-label, multicenter, randomized phase 2, non-inferiority study (NCT04603183). Key inclusion criteria were adult pts with HR+/HER2- ABC, no prior systemic therapy for ABC, ECOG 0-1, measurable disease, and ≥1 aggressive disease criteria: visceral metastases, grade 3 and/or negative progesterone receptor on primary tumor, LDH >1.5 x ULN, and/or disease progression on or within 36 months after completing adjuvant ET. Pts were randomized 1:1 to arm A: abemaciclib (oral 150 mg twice/day in 28-day cycles) + letrozole [oral 2.5 mg/day] or fulvestrant [IM 500 mg/days 1, 15, 29 and once monthly thereafter] at investigator criteria; or arm B: paclitaxel (IV 90 mg/m², days 1, 8, and 15 every 28 days) x 12 weeks followed by abemaciclib + ET (letrozole or fulvestrant at investigator criteria). Stratification factor was the presence of visceral disease. Primary endpoint was 12-week overall response rate (ORR) as per blinded independent central review using RECIST 1.1. Key secondary endpoint was safety.

Results

Between June 2021 and January 2024, 162 pts from 29 sites were randomized to arm A (n=80; 72.5% letrozole) or arm B (n=82). Pts characteristics were balanced. Median age was 58 years (range 26–85). Visceral disease was present in 64% pts, 36% had ≥3 metastatic sites, and 30% had de novo ABC. Primary endpoint was met with 12-week ORR 59% in arm A and 40% in arm B (OR: 2.12 [95% CI, 1.13–3.96]; p=0.019). Safety analysis is ongoing and will be presented at the meeting.

Conclusions

ABIGAIL confirms that first-line abemaciclib + ET achieves a higher early ORR compared to paclitaxel in HR+/HER2- ABC pts with aggressive disease criteria.

Clinical trial identification

NCT04603183.

Editorial acknowledgement

Legal entity responsible for the study

Medica Scientia Innovation Research (MEDSIR).

Funding

Eli Lilly.

Disclosure

J. Cortés: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Lilly, Merck Sharp& Dohme, Leuko, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics, Jazz Pharmaceuticals, AbbVie, Scorpion Therapeutics, Biocon; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Eisai, Pfizer, Lilly, Merck Sharp& Dohme, Daiichi Sankyo; Financial Interests, Personal, Other, Consulting/advisor: Expres2ion Biotechnologies; Financial Interests, Personal, Other, consulting: Bridgebio; Financial Interests, Personal, Stocks/Shares: MAJ3 Capital; Financial Interests, Personal, Stocks/Shares, (relative): Leuko; Financial Interests, Institutional, Research Grant: Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Queen Mary University of London; Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo, Pfizer, Gilead, AstraZeneca, Steamline Therapeutics; Other, travel cost and expenses: Merck Sharp&Dhome. S. Di Cosimo: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Advisory Board: MEDSIR, Pierre-Fabre, IQVIA. I. Blancas López-Barajas: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Eisai, Gilead, Grünenthal, GSK, Lilly, MSD, Novartis, Pfizer, Pierre-Fabre, Roche, Seagen; Financial Interests, Personal, Other, Medical monitor: Medical Science Innovation Research (MEDSIR); Financial Interests, Institutional, Funding: AstraZeneca, Lilly, Roche, Agendia; Financial Interests, Institutional, Research Grant: Pfizer; Other, Support for attending meetings and/or travel: AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Gilead, Lilly, Novartis, Pfizer, Roche, Pierre Fabre. E. López-Miranda: Financial Interests, Personal, Royalties: AstraZeneca, Seagen, Lilly, Daichii Sankyo; Financial Interests, Personal, Advisory Role: AstraZeneca, Daichii Sankyo; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Speaker’s Bureau: Lilly, AstraZeneca; Financial Interests, Personal, Other: Gilead, Roche. J. Ponce: Financial Interests, Personal, Advisory Board: Seattle Genetics, Novartis, AstraZeneca/Daiichi Sankyo, Roche, Pierre Fabré; Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, AstraZeneca/Daiichi Sankyo, Seattle Genetics, Lilly. V. Iranzo: Financial Interests, Personal, Invited Speaker: Ipsen, Roche, Novartis, Pfizer, Eisai, Daiichi Sankyo, AstraZeneca, Pierre-Fabre, Teva, Seagen; Financial Interests, Personal, Advisory Board: Genomic Health, Roche, Pfizer, Advanced Accelerator Applications, AstraZeneca. A. Garrido: Financial Interests, Personal, Full or part-time Employment: MEDSIR. D. Alcalá-López: Financial Interests, Institutional, Full or part-time Employment: MEDSIR. L. Mina: Financial Interests, Full or part-time Employment: MEDSIR. A. Llombart Cussac: Financial Interests, Personal, Research Funding: Roche, Agendia, Lilly, Pfizer, Novartis, Merck Sharp & Dome, Gilead, Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Lilly, Roche, Pfizer, Novartis; Financial Interests, Personal, Speaker’s Bureau: Lilly, AstraZeneca, Merck Sharp & Dome; Financial Interests, Personal, Other: Roche, Pfizer, AstraZeneca; Financial Interests, Personal, Stocks or ownership: MEDSIR, Initia-Research. All other authors have declared no conflicts of interest.