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A phase Ib study of abemaciclib with therapies for metastatic breast cancer.

2015; Lippincott Williams & Wilkins; Volume: 33; Issue: 15_suppl Linguagem: Inglês

10.1200/jco.2015.33.15_suppl.522

1527-7755

Sara M. Tolaney, Muralidhar Beeram, J. Thaddeus Beck, Alison Conlin, Elizabeth Claire Dees, Maura N. Dickler, Teresa Helsten, Paul Conkling, William J. Edenfield, Donald Richards, P. Kellie Turner, Na Cai, Edward M. Chan, Shubham Pant, Carlos Becerra, Kevin Kalinsky, Shannon Puhalla, Brent N. Rexer, Howard A. Burris, Matthew P. Goetz,

Chronic Lymphocytic Leukemia Research

522 Background: Abemaciclib, an inhibitor of cyclin dependent kinases CDK4 and CDK6, demonstrated safety and clinical activity as a single agent for hormone receptor positive (HR+) metastatic breast cancer (MBC) irrespective of HER2 amplification (Tolaney, SABCS 2014). This study (NCT02057133) evaluates safety, pharmacokinetics (PK), and antitumor activity of abemaciclib combined with endocrine or HER2-targeted therapies for MBC. Methods: Patients (pts) in 6 cohorts received abemaciclib 150-200 mg every 12 hours (Q12H) with letrozole 2.5 mg/d (Part A), anastrozole 1 mg/d (Part B), tamoxifen 20 mg/d (Part C), exemestane 25 mg/d (Part D), exemestane 25 mg/d + everolimus 5 mg/d (Part E), or trastuzumab 6-8 mg/kg every 21 days (Part F). Pts in Parts A-E had HR+, HER2- MBC and in Part F had HER2+ MBC. Eligibility included measurable disease or nonmeasurable bone disease by RECIST v1.1, ECOG performance status ≤ 1, no prior chemotherapy for metastatic disease (Parts A-E), and ≥ 1 chemotherapy regimen for metastatic disease (Part F). Abemaciclib was given continuously until progression. Patients were assessed every 28 days in Parts A-E and every 21 days in Part F. Dose escalation cohorts of ≥ 3 pts receiving abemaciclib at 150 mg and 200 mg Q12H were included in Parts E and F. Results: A total of 65 pts started treatment with abemaciclib (200mg Q12H) by 16-Dec-2014 in Parts A-D. Pts had a median age of 57 years (range: 28-77) and a median of 3 prior systemic therapies (range: 1-8) for breast cancer. The most common ( ≥ 20% overall in Parts A-D) possibly related treatment-emergent adverse events (TEAEs) (all grades %, G3 %) were diarrhea (95, 31), fatigue (71, 14), nausea (62, 6), neutropenia (31, 17), abdominal pain (31, 3), decreased appetite (29, 0), vomiting (28, 3), and anemia (25, 0). Diarrhea was manageable with antidiarrheal agents or dose reduction. No G4/5 TEAEs occurred. The disease control rate (CR + PR + SD) was 67% for Parts A+B [nonsteroidal aromatase inhibitors (36 pts)] with 2 confirmed PRs and 75% for Part C [tamoxifen (16 pts)]. Safety, PK, and efficacy results will be updated at presentation. Conclusions: Combinations of abemaciclib with endocrine therapies demonstrate manageable safety and early clinical evidence of antitumor activity. Clinical trial information: NCT02057133.