Abemaciclib With Fulvestrant/Aromatase Inhibitor in HR+, HER2- Breast Cancer: Pooled Analysis of MONARCH 2/3

Abemaciclib is a continuous oral administration, selective cyclin-dependent kinases 4 and 6 inhibitors (CDK4 & 6i). Abemaciclib, in combination with fulvestrant, improved overall survival (OS) and progression-free survival (PFS) significantly in women with HR+, HER2-advanced breast cancer (ABC) in the MONARCH 2 (M2) trial. Similarly, abemaciclib showed a PFS advantage in conjunction with nonsteroidal aromatase inhibitors (NSAI) in women with HR+ and HER2- ABC in MONARCH 3 (M3). The objective response rate (ORR) for endocrine-naive (EN) patients with detectable illnesses who participated in the M2 and M3 studies and received abemaciclib is presented here. Women with HR+ and HER2- ABC participated in two Phase 3 double-blind investigations, M2 (NCT02107703) and M3 (NCT02246621). Abemaciclib (150 mg or 200 mg BID) or placebo was randomly assigned to all patients in M2 who had previously received fulvestrant (500 mg, per label). Twenty patients were enrolled in the abemaciclib arm, all with detectable baseline illness. Ninety more patients with evaluable illness in EN were included in a single-arm extension of the M2 study who received abemaciclib.

The patients in EN M2 had not previously been treated with endocrine therapy (ET) or chemotherapy in the metastatic situation. Stratified by prior neoadjuvant or adjuvant ET (NSAI, no ET, or other), 142 M3 EN participants with measurable disease were randomized to abemaciclib (150 mg BID) or placebo, and all participants received NSAI (anastrozole 1 mg or letrozole 2.5 mg daily). Analyzed subjects included M2 and M3 patients with evaluable illness treated with abemaciclib (N=252). The objective response rate (% of patients with the best response of complete [CR] or partial [PR]) was the primary goal. Time to progression (PFS), complete response (CR), partial response (PR), stable disease (SD), duration of response (DoR), and safety were the secondary objectives.

A total of 252 people with quantifiable disease participated in EN (43.7% M2, 56.3% M3) across 21 countries. The average age of the participants was 59. N=167 (66.3%) of the patients had involvement in 3 metastatic organ locations. The overall response rate (ORR) among all patients with EN was 57.5% (95% CI 51.4-63.6). The CBR’s 95% confidence interval (CI) was 73.5-83.6, and the CI for the DCR was 89.7-96.0. The M2 EN supplementary PFS and DoR data are not complete yet. There were no fresh warning signs detected. As with the M2 and M3 populations, the safety profile was consistent with those previously reported. Compared to 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), the primary analysis of confirmed ORR in M2 and M3 EN participants with the measurable disease is encouraging. Regarding safety, this study has a profile consistent with that of the core M2 and M3 investigations.

Source:https://www.abstractsonline.com/pp8/#!/10462/presentation/851

Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT02107703

Matthew P. Goetz, Jose Luis Gonzalez Trujillo, Masakazu Toi, Jens Huober, Antonio Llombart-Cussac, Wei Zhang, Holly Knoderer, Nadine Haddad, Gertjan Van Hal and George W. Sledge/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/(2020). Abstractsonline.com. https://www.abstractsonline.com/pp8/#

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