Abemaciclib, an oral, continuously dosed cyclin-dependent kinase 4 & 6 (CDK 4 & 6) inhibitor, improves progression free survival (PFS) in combination with endocrine therapy (ET) in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), metastatic breast cancer (MBC) in the phase III MONARCH2 and 3 studies. In the phase II nextMONARCH study, primary analysis of PFS and ORR confirmed the robust single-agent activity of abemaciclib in heavily pretreated HR+, HER2- MBC with no significant improvement by addition of tamoxifen. We here report the final 24-month overall survival results.
nextMONARCH was a multicenter, randomized, open-label phase II trial of abemaciclib in women with heavily pretreated HR+, HER2- MBC whose disease progressed on or after ET and chemotherapy. Patients were randomized 1:1:1 to abemaciclib 150 mg + tamoxifen 20 mg (A+T), or abemaciclib 150 mg (A-150) or abemaciclib 200 mg plus prophylactic loperamide (A-200). Final OS analysis occurred 24 months after the last patient entered treatment. OS was a preplanned secondary endpoint.
At the time of data cutoff (28-June-2019), 12 of the 234 patients enrolled were still ongoing on study treatment. Median follow-up was 27.2 months. Median OS was 24.2 months in the A+T arm, compared to 20.8 months in A-150, and 17.0 months in A-200 (A+T vs. A-150: HR 0.620 (95% CI [0.397, 0.969] p=0.034); A-150 vs. A-200: HR 0.956 (95% CI [0.635, 1.438] p=0.832)). The primary PFS endpoint and ORR were unchanged at the 24-month analysis. Common treatment-emergent adverse events (TEAEs) across all abemaciclib arms occurring in ≥25% of patients included diarrhea (61.1%), neutropenia (49.6%), anemia (40.6%), nausea (36.3%), leukopenia (30.8%), fatigue (29.9%) and abdominal pain (27.4%).
Addition of tamoxifen to abemaciclib provided a statistically significant median OS improvement compared to abemaciclib monotherapy in this heavily pretreated HR+, HER2- MBC patient population. PFS was consistent with the primary results of nextMONARCH with no significant difference. No new safety findings were observed.
NCT02747004.
Nicholas Pulliam, PhD - Eli Lily and Company.
Eli Lilly and Company.
Eli Lilly and Company.
E.P. Hamilton: Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Fred Hutchinson; Research grant/Funding (institution): OncoMed; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): StemCentrx; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Curis; Research grant/Funding (institution): Verastem; Research grant/Funding (institution): Zymeworks; Research grant/Funding (institution): Syndax; Research grant/Funding (institution): Lycera; Research grant/Funding (institution): Rgenix; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Mersana; Research grant/Funding (institution): Millenium; Research grant/Funding (institution): TapImmune; Research grant/Funding (institution): Cascadian; Research grant/Funding (institution): Eli Lilly and Company; Research grant/Funding (institution): BerGenBio; Research grant/Funding (institution): Medication; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): Kamdon; Research grant/Funding (institution): BI; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): H3 Biomedicines; Research grant/Funding (institution): Radius; Research grant/Funding (institution): Acerta; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Macrogenics. J. Cortés: Research grant/Funding (institution): Puma C; Honoraria (self), Advisory/Consultancy: Celgene; Advisory/Consultancy: Cellestia; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Biothera Pharmaceutical; Advisory/Consultancy: Merus; Advisory/Consultancy: Seattle Genetics; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy: Erytech; Advisory/Consultancy: Athenex; Advisory/Consultancy: Polyphor; Honoraria (self), Advisory/Consultancy: Eli Lilly and Company; Advisory/Consultancy: Servier; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Sharp&Dohme; Advisory/Consultancy: GSK; Advisory/Consultancy: Leuko; Advisory/Consultancy: Bioasis; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Samsung Bioepis; Research grant/Funding (institution): Ariad Pharmaceuticals; Research grant/Funding (institution): Baxalta GMBH/Servier Affaires; Research grant/Funding (institution): Bayer Healthcare; Research grant/Funding (institution): Guardanth Health; Research grant/Funding (institution): Piqur Therapeutics. K. Petrakova: Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): BMS. G. Jerusalem: Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Honoraria (institution), Research grant/Funding (self), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Celgene; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Puma Biotechnology. J. Huober: Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Pfizer; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Celgene; Advisory/Consultancy: Hexal; Travel/Accommodation/Expenses: Daiichi. All other authors have declared no conflicts of interest.