273O - nextMONARCH: Final overall survival analysis of abemaciclib monotherapy or in combination with tamoxifen in patients with HR+, HER2- metastatic breast cancer

Background

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.

Methods

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.

Results

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%).

Conclusions

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.

Clinical trial identification

NCT02747004.

Editorial acknowledgement

Nicholas Pulliam, PhD - Eli Lily and Company.

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

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.