45O - Abemaciclib plus fulvestrant in East Asian women with HR+, HER2- advanced breast cancer: Overall survival from MONARCH 2

Background

MONARCH 2 demonstrated that the addition of abemaciclib, an oral CDK4 & 6 inhibitor dosed on a continuous schedule, to fulvestrant (F) significantly improved progression-free survival (PFS) (median 16.4 v 9.3 mo; HR: 0.553; p<.001) and resulted in an overall survival (OS) benefit of 9.4 months compared to placebo (P) plus (+) F (median 46.7 v 37.3 mo; HR: 0.757; p=.01) for patients (pts) with HR+, HER2- advanced breast cancer (ABC) who progressed on endocrine therapy (ET). Consistent with the ITT population and pts from other regions, PFS benefit was previously reported in East Asian pts (Japan, Korea, Taiwan) with a median of 21.2 mo for abemaciclib + F and 11.6 mo for P + F (HR: 0.520; p<.001). The safety profile was manageable. Here we report OS and other updated efficacy and safety data in East Asian pts.

Methods

MONARCH 2 was a phase III, global, double-blind, 2:1 randomized trial of abemaciclib + F or P + F in pts (N=669) with HR+, HER2- ABC who progressed on ET. Pre- or perimenopausal (with ovarian suppression) and postmenopausal women received abemaciclib or P (150mg Q12H) and F (500mg per label). Exploratory subgroup analyses were conducted among East Asian pts in the ITT population. HR in East Asian pts was estimated using Cox model, with the log-rank test performed.

Results

In the ITT population, 212 East Asian pts were randomized to abemaciclib + F (n=147) or P + F (n=65). At data cutoff (20June2019), 89 OS events were observed in East Asian pts, with a median OS not reached for abemaciclib + F and 48.9 mo for P + F (HR: 0.798 95% CI 0.515, 1.235; p=.38). The OS rates at 42 mo were 64% (95% CI 55.5, 71.8) for abemaciclib + F and 53% (95% CI 39.9, 64.6) for P + F. PFS2 (HR: 0.588 95% CI 0.420, 0.823; p=.001), time to chemotherapy (HR: 0.601 95% CI 0.411, 0.877; p=.008) and chemotherapy-free survival (HR: 0.573 95% CI 0.402, 0.815; p=.002) were all significantly improved in pts treated with abemaciclib + F. No new safety signals were reported and the safety profile was consistent with previously reported safety data in East Asian pts.

Conclusions

Consistent with previous reports in the ITT population, abemaciclib + F was an effective and tolerable treatment for East Asian patients with HR+, HER2- ABC who progressed on ET.

Clinical trial identification

NCT02107703.

Editorial acknowledgement

Writing and editorial support provided by Sarah C. Nabinger (Eli Lilly and Company).

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

C-S. Huang: Advisory/Consultancy, Research grant/Funding (institution), non-financial support: Eli Lilly and Company; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Research grant/Funding (institution), Travel/Accommodation/Expenses, non-financial support: AstraZeneca; Research grant/Funding (institution): EirGenix; OBI Pharma; MSD; Daiichi Sankyo; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses, non-financial support: Roche. M. Toi: Honoraria (self), Research grant/Funding (institution): Chugai, Takeda, Pfizer; Officer/Board of Directors: Organisation for Oncology and Translational Research; Officer/Board of Directors: Kyoto Breast Cancer Research Network; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), advisory role for drug development: Kyowa-Hakko-Kirin; Honoraria (self), Research grant/Funding (institution): Taiho; Research grant/Funding (institution), Officer/Board of Directors: JBCRG association; Honoraria (self), Research grant/Funding (institution): Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), advisory role for drug development: Daiichi-Sankyo; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self): Eli Lilly and Company; Honoraria (self): MSD; Honoraria (self): Genomic Health; Honoraria (self): Novartis; Honoraria (self), Honoraria for advisory meeting: Konica Minolta; Research grant/Funding (institution): Astellas, AFI Technologies; Honoraria (self), Honoraria for advisory meeting: BMS; Honoraria (self), Research grant/Funding (institution): Shimadzu; Honoraria (self): Yakult; Honoraria (self), Research grant/Funding (institution): Nippon Kayaku; Advisory/Consultancy: Athenex Oncology, Bertis. H. Iwata: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly and Company-Japan; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Chugai Pharm; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Daiichi-Sankyo; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Kyowa Hakko Kirin; Honoraria (self), Research grant/Funding (institution): Eisai; Research grant/Funding (institution): GlaxoSmithklin; Research grant/Funding (institution): Nihon Kayaku; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Boehringer Ingelheim. J. Sohn: Research grant/Funding (institution): MSD; Roche; Novartis; AstraZeneca; Eli Lilly and Company; Pfizer; Bayer; GSK; Contessa; Daiichi Sankyo. N. Masuda: Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Eli Lilly and Company; Honoraria (self), Research grant/Funding (institution): Eisai; Honoraria (self), Research grant/Funding (institution): Takeda; Honoraria (self), Research grant/Funding (institution): Kyowa-Kirin; Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Daiichi-Sankyo. S-A. Im: Advisory/Consultancy: Amgen; Hanmi Corp; MSS; Eli Lilly and Company; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Eisai; Pfizer; Roche; Dae-Woong. Y. Lu; N. Haddad; S. Sakaguchi; K. Hurt: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly and Company. P. Neven: Advisory/Consultancy, fees to Institution: Pfizer; Novartis; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, fees to Institution: Eli Lilly and Company; Advisory/Consultancy, fees to Institution: Roche; Research grant/Funding (self): Kom op Tegen Kanker; Research grant/Funding (institution), Institution receives fees for my lecture/attendance at scientific exchange meetings: My Institution. A. Llombart-Cussac: Honoraria (self), Research grant/Funding (institution), personal fees and non-financial support: Novartis; Roche; AstraZeneca; Pfizer; Eli Lilly and Company; Research grant/Funding (institution), non-financial support: Eisai; Honoraria (self), Research grant/Funding (institution), personal fees: Genomichealth; GSK Tesaro; Honoraria (self), personal fees: MSD; Honoraria (self), personal fees and non-financial support: Bristol; Shareholder/Stockholder/Stock options, stock, patents and intellectual property: MedSIR. G. Sledge: Research grant/Funding (institution), Travel/Accommodation/Expenses: Eli Lilly and Company; Officer/Board of Directors: Tessa Therapeutics; Research grant/Funding (institution): Pfizer; Advisory/Consultancy, SAB: Verseau Inc; Advisory/Consultancy, SAB: Syndax. All other authors have declared no conflicts of interest.