MONARCH 3: Updated time to chemotherapy and disease progression following abemaciclib plus aromatase inhibitor (AI) in HR+, HER2- advanced breast cancer (ABC)

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      Abstract

      Background

      In MONARCH 3, a randomized, double-blind, phase 3 trial; continuous dosing of abemaciclib in combination with an AI (anastrozole or letrozole) conferred significant clinical benefit to postmenopausal women with HR+, HER2- ABC. We here report data from an additional 12 months of follow-up in this trial including analysis for clinically prognostic subgroups (Di Leo et al., 2018).

      Methods

      From the 31 October 2018 data cutoff, exploratory intermediate efficacy parameters including time to subsequent chemotherapy ([TCT] time from randomization to first chemotherapy [CT]) and time to second disease progression ([PFS2] time from randomization to discontinuation date of first post-discontinuation treatment [PDT], or starting date of the secondPDT, or death) were assessed. TCT and PFS2 were analyzed using the Kaplan-Meier method in the intent to treat (ITT) and subgroups previously identified as significantly prognostic.

      Results

      Table326P
      TCTPFS2
      Abemaciclib + AI Events/NPlacebo + AI Events/NHR (95% CI)Abemaciclib + AI Events/NPlacebo + AI Events/NHR (95% CI)
      ITT
      93/32882/1650.513 (0.380, 0.691)152/328106/1650.637 (0.495, 0.819)
      ECOG PS
       134/13636/610.342 (0.214, 0.548)64/13645/610.504 (0.344, 0.740)
       059/19246/1040.639 (0.435, 0.940)88/19261/1040.762 (0.549, 1.059)
      Bone-only disease
       Yes13/6916/400.440 (0.211, 0.914)21/6923/400.523 (0.289, 0.945)
       No80/25966/1250.495 (0.357, 0.686)131/25983/1250.660 (0.501, 0.871)
      Liver metastases
       Yes21/4721/310.572 (0.313, 1.048)32/4725/310.677 (0.401, 1.142)
       No72/28161/1340.504 (0.358, 0.709)120/28181/1340.663 (0.500, 0.881)
      Progesterone receptor status
       Positive66/25557/1280.529 (0.371, 0.753)115/25578/1280.694 (0.520, 0.927)
       Negative25/7024/360.414 (0.236, 0.725)35/7027/360.537 (0.325, 0.889)
      Tumor grade
       High22/6521/320.369 (0.203, 0.672)27/6523/320.418 (0.240, 0.730)
      Intermediate/Low52/17948/960.512 (0.345, 0.757)86/17963/960.671 (0.484, 0.931)
      Treatment-free interval
       <36 months15/4418/320.465 (0.234, 0.924)21/4424/320.506 (0.281, 0.910)
       ≥36 months32/9518/410.798 (0.448, 1.422)48/9524/410.895 (0.548, 1.461)

      Conclusions

      Addition of abemaciclib to AI prolonged PFS2 and TCT in the ITT and all prognostic subgroups.

      Clinical trial identification

      NCT02246621.

      Editorial acknowledgement

      Medical writing support was provided by Anchal Sood and editorial assistance by Rod Everhart of Syneos Health, and funded by Eli Lilly and Company.

      Legal entity responsible for the study

      Eli Lilly and Company.

      Funding

      Eli Lilly and Company.

      Disclosure

      M. Martín: Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Eli Lilly and Company; Honoraria (self): Taiho Oncology; Honoraria (self): Pharmamar; Honoraria (self): Roche/Genentech. S. Johnston: Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Advisory / Consultancy: Eli Lilly and Company; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Pfizer; Advisory / Consultancy, Research grant / Funding (self): Puma Biotechnology; Speaker Bureau / Expert testimony: Eisai. J. Huober: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Eli Lilly and Company; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy: Hexal; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (self), Advisory / Consultancy: Abbvie. A. Di Leo: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Celgene; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Eisai; Honoraria (self), Advisory / Consultancy: Genomic Health; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Eli Lilly and Company; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Daiichi Sankyo; Advisory / Consultancy: Genentech; Advisory / Consultancy: Ipsen; Advisory / Consultancy, Travel / Accommodation / Expenses: Puma Biotechnology. V.A. Andre: Shareholder / Stockholder / Stock options, Full / Part-time employment: Eli Lilly and Company. H.R. Martin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Eli Lilly and Company. M.C. Hardebeck: Shareholder / Stockholder / Stock options, Full / Part-time employment: Eli Lilly and Company. M.P. Goetz: Honoraria (self): Genomic Health; Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly and Company; Advisory / Consultancy: Biovica; Advisory / Consultancy: Novartis; Advisory / Consultancy: Sermonix; Advisory / Consultancy: Context Pharm; Research grant / Funding (institution): Pfizer. All other authors have declared no conflicts of interest.