Abstract CT044: MONARCH 1: Final overall survival analysis of a phase 2 study of abemaciclib, a CDK4 and CDK6 inhibitor, as monotherapy, in patients with HR+/HER2- breast cancer, after chemotherapy for advanced disease
Authors: Rugo Hope S. , Tolaney Sara M. , Cortés Javier , Diéras Véronique , Patt Debra A. , Wildiers Hans , Nanda Shivani , Koustenis Andrew G. , Dickler Maura N. , Baselga José 
Published: July 2017

Abstract
Background: Abemaciclib is an oral, selective inhibitor of CDK4 and CDK6 dosed on a continuous schedule. MONARCH 1 (NCT02102490) is a phase 2 single-arm study designed to evaluate safety and efficacy of abemaciclib monotherapy in women with HR+/HER2- MBC whose disease progressed on or after endocrine therapy and chemotherapy. Final analysis of the primary endpoint, objective response rate (ORR) at 12 months (mo), showed that abemaciclib monotherapy induced objective tumor responses in patients (pts) with refractory HR+/HER2- MBC following multiple prior therapies. Treatment was well tolerated, allowing prolonged exposure to therapy. We report the final 18 mo overall survival results.
Methods: Eligible pts had measurable disease, ECOG PS of 0/1, no CNS metastases, and received at least 1 but no more than 2 lines of chemotherapy in the metastatic setting. Abemaciclib (200 mg) was administered orally on a continuous schedule every 12 hours until disease progression. The primary objective was to evaluate ORR per RECIST v1.1. at 12 mo after the last pt enrolled. Secondary objectives included duration of response (DoR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR = CR + PR + SD), clinical benefit rate (CBR= CR + PR + SD ≥ 6 mo) and safety. Final OS analysis occurred 18 mo after the last pt was enrolled.
Results: A total of 132 pts received abemaciclib monotherapy. The primary endpoint of ORR by investigator assessment at 12 mo was 19.7% (95% CI: 13.3, 27.5) and did not change at 18 mo. Of the 26 responding pts, 19 (73.1%) had responses ≥ 6 mo, and 6 pts still on treatment have response durations ranging from 9.5+ to 20.5+ mo. There was no change at 18 mo vs 12 mo for DCR (67.4%) or CBR (42.4%). Median PFS (6.0 mo, 95% CI: 4.2, 7.5) and median DoR (8.9 mo, 95% CI: 6.1, 14.0) were also consistent with 12 mo follow up. At the 18 mo update, 7 pts (5.3%) remained on treatment (6 PR and 1 SD). At 18 mo, the median OS was 22.3 mo (95% CI: 17.7, NR), and the survival rate was 58.7%. TEAEs ≥ Grade 3 were experienced by 93 pts (70.5%) at 18 mo, compared to 90 pts (68.2%) at 12 mo. The most common Grade 3/4 TEAEs were neutropenia (25.0%), diarrhea (19.7%), fatigue (13.6%), leukopenia (6.8%), anemia (4.5%) and nausea (4.5%). Treatment discontinuations due to AEs were infrequent (7.6 %).
Conclusions: The results of the 18 month analysis are consistent with the 12 month results of MONARCH 1. Median OS was 22.3 months. The efficacy results from the MONARCH 1 study indicate that continuous administration of single-agent abemaciclib induces durable confirmed tumor responses. There were no clinically significant changes in safety. The results of the 18 month analysis support the earlier results and indicate that single-agent abemaciclib may offer a more favorable benefit-risk profile than expected from available cytotoxic chemotherapies.
Citation Format: Hope S. Rugo, Sara M. Tolaney, Javier Cortés, Véronique Diéras, Debra A. Patt, Hans Wildiers, Shivani Nanda, Andrew G. Koustenis, Maura N. Dickler, José Baselga. MONARCH 1: Final overall survival analysis of a phase 2 study of abemaciclib, a CDK4 and CDK6 inhibitor, as monotherapy, in patients with HR+/HER2- breast cancer, after chemotherapy for advanced disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT044. doi:10.1158/1538-7445.AM2017-CT044