Abstract P1-18-21: Abemaciclib plus fulvestrant or nonsteroidal aromatase inhibitor in participants with HR+, HER2- breast cancer - A pooled analysis of the endocrine therapy-naïve participants with measurable disease in MONARCH 2 and MONARCH 3
Authors: Goetz Matthew P. , Trujillo Jose Luis Gonzalez , Toi Masakazu , Huober Jens , Llombart-Cussac Antonio , Zhang Wei , Knoderer Holly , Haddad Nadine , Van Hal Gertjan , Sledge George W. 
Published: March 2022

Abstract
Background: Abemaciclib is an oral selective cyclin dependent kinases 4 & 6 inhibitor (CDK4 & 6i), administered on a continuous schedule. Abemaciclib demonstrated significant overall survival (OS) and progression-free survival (PFS) benefit in women with hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) in combination with fulvestrant in MONARCH 2 (M2). Similarly, abemaciclib demonstrated a PFS benefit in women with HR+, HER2- ABC in combination with nonsteroidal aromatase inhibitors (NSAI) in MONARCH 3 (M3). Here, we present the objective response rate (ORR) from the pooled cohort of endocrine-naïve (EN) participants with measurable disease enrolled in M2 and M3 that received abemaciclib. Methods: M2 (NCT02107703) and M3 (NCT02246621) were double-blind, Phase 3 studies in women with HR+, HER2- ABC. In M2, all patients received fulvestrant (500 mg, per label) and were randomized to receive either abemaciclib (150 mg or 200 mg BID) or placebo. 20 EN participants with measurable disease at baseline were enrolled to the abemaciclib arm. A M2 single arm addendum enrolled 90 additional EN participants with measurable disease to abemaciclib. EN M2 participants had received no previous endocrine therapy (ET) in any setting nor prior chemotherapy in the metastatic setting. In M3, all participants received NSAI (anastrozole 1 mg or letrozole 2.5 mg daily) and were randomized to receive abemaciclib (150 mg BID) or placebo based on stratification factors including prior neoadjuvant or adjuvant ET (NSAI, no ET or other) with 142 M3 EN participants with measurable disease randomized to abemaciclib. The population for analysis consisted of a pooled EN cohort from M2 and M3 with measurable disease that received abemaciclib (N=252). The primary endpoint was investigator-assessed ORR (percentage of participants with best response of complete [CR] or partial response [PR]). The secondary endpoints included PFS, clinical benefit rate (CBR = CR + PR + stable disease persistent for ≥6 months), disease control rate (DCR = CR + PR + SD), duration of response (DoR), and safety. Results: 252 EN participants with measurable disease (43.7% M2, 56.3% M3) from 21 countries were included in the analysis population. Median participant age was 59.0 years. Most patients (n=167 [66.3%]) had ≥3 metastatic organ sites involved. In the pooled EN cohort, confirmed ORR was 57.5% (95% CI 51.4-63.6). CBR was 78.6% (95% CI 73.5-83.6) and DCR was 92.9% (95% CI 89.7-96.0). PFS and DoR data for the M2 EN addendum are not yet mature. No new safety signals were observed. The safety profile was consistent with the previously reported M2 and M3 populations. Conclusion: Primary analysis of confirmed ORR in M2 and M3 EN participants with measurable disease compares favorably with previously reported ORR for fulvestrant monotherapy (FALCON study: 46% unconfirmed; FIRST study: 36% unconfirmed) or NSAI (PALOMA-2 study: 44.8% confirmed; MONALEESA-2: 34% unconfirmed) in participants with a similar disease state. The safety profile is similar to that reported in the primary M2 and M3 main studies.
Citation Format: Matthew P. Goetz, Jose Luis Gonzalez Trujillo, Masakazu Toi, Jens Huober, Antonio Llombart-Cussac, Wei Zhang, Holly Knoderer, Nadine Haddad, Gertjan Van Hal, George W. Sledge, Jr. Abemaciclib plus fulvestrant or nonsteroidal aromatase inhibitor in participants with HR+, HER2- breast cancer - A pooled analysis of the endocrine therapy-naïve participants with measurable disease in MONARCH 2 and MONARCH 3 [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-18-21.