ENDOCRINE THERAPY AND ABEMACICLIB COMBINATION FOR THE ADJUVANT TREATMENT OF NODE-POSITIVE, EARLY STAGE, HORMONE RECEPTOR-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2-NEGATIVE BREAST CANCER

Abstract

The present invention discloses an adjuvant treatment of node-positive, early stage, hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) breast cancer comprising administering an effective amount of an endocrine therapy in combination with an effective amount of abemaciclib or a pharmaceutically acceptable salt thereof.

Claims

1.-16. (canceled)

17. A method of treating a patient with a prior diagnosis of node-positive, early stage, HR+, HER2− breast cancer which has been resected, comprising administering an effective amount of an endocrine therapy in combination with an effective amount of abemaciclib or a pharmaceutically acceptable salt thereof, wherein said administering is after resection in an adjuvant setting.

18. A method of increasing distant relapse-free survival in a patient with a prior diagnosis of node-positive, early stage, HR+, HER2− breast cancer which has been resected, comprising administering an effective amount of an endocrine therapy in combination with an effective amount of abemaciclib or a pharmaceutically acceptable salt thereof.

19. The method according to claim 17, wherein the endocrine therapy is tamoxifen or a pharmaceutically acceptable salt thereof.

20. The method according to claim 18, wherein the endocrine therapy is tamoxifen or a pharmaceutically acceptable salt thereof.

21. The method according to claim 17, wherein the endocrine therapy is letrozole.

22. The method according to claim 18, wherein the endocrine therapy is letrozole.

23. The method according to claim 17, wherein the endocrine therapy is anastrozole.

24. The method according to claim 18, wherein the endocrine therapy is anastrozole.

25. The method according to claim 17, wherein the endocrine therapy is exemestane.

26. The method according to claim 18, wherein the endocrine therapy is exemestane.

27. The method according to claim 17, wherein the abemaciclib or the salt thereof is administered at 150 mg twice daily.

28. The method according to claim 18, wherein the abemaciclib or the salt thereof is administered at 150 mg twice daily.

29. The method according to claim 17, wherein the abemaciclib or the salt thereof is administered at 100 mg twice daily.

30. The method according to claim 18, wherein the abemaciclib or the salt thereof is administered at 100 mg twice daily.

Description

EXAMPLE 1

A Randomized, Open-Label, Phase 3 Study of Abemaciclib Combined with Standard Adjuvant Endocrine Therapy Versus Standard Adjuvant Endocrine Therapy Alone in Patients with High Risk, Node Positive, Early Stage, Hormone Receptor Positive, Human Epidermal Receptor 2 Negative, Breast Cancer

[0034] The primary objective of this study is to evaluate the efficacy, in terms of invasive disease-free survival (IDFS), as defined by the STEEP System, for patients with HR+, HER2− early stage breast cancer for abemaciclib 150 mg twice daily plus adjuvant endocrine therapy versus adjuvant endocrine therapy alone.

The secondary objectives of this study is to [0035] evaluate the efficacy, in terms of IDFS, for patients with HR+, HER2− early stage breast cancer with Ki67 index≥20% (both Cohort 1 and Cohort 2 by central lab); [0036] evaluate the efficacy of abemaciclib plus adjuvant endocrine therapy versus adjuvant endocrine therapy alone in terms of distant relapse-free survival (DRFS) and overall survival (OS); [0037] assess the safety profile of abemaciclib plus adjuvant endocrine therapy compared to adjuvant endocrine therapy alone; [0038] evaluate the relationship between abemaciclib exposure and clinical (efficacy and safety) outcomes; [0039] evaluate abemaciclib plus adjuvant endocrine therapy, versus adjuvant endocrine therapy alone, in terms of general oncology and breast cancer self-reported health-related quality of life (Functional Assessment of Cancer Therapy [FACT]-Breast 37-item questionnaire), endocrine therapy-specific symptoms (Functional Assessment of Cancer Therapy-Endocrine Symptoms (Version 4) [FACT-ES] 19-item subscale and 2 Functional Assessment of Chronic Illness Therapy Item Library [FACIT] (Version 2) sourced items of cognitive symptoms and 3 FACIT-sourced items for bladder symptoms), and fatigue experienced during abemaciclib and/or endocrine therapy (FACIT-Fatigue 13-item subscale); and [0040] evaluate health status to inform decision modeling for health economic evaluation using the EuroQol five-dimension five-level questionnaire.

[0041] The study will screen approximately 4200 patients, and approximately 3580 patients will be enrolled and subdivided into 2 cohorts: those eligible based on nodal status, tumor size, or grade regardless of Ki67 status, Cohort 1, and those with at least 1 positive node and eligible exclusively based on a Ki67 status, Cohort 2 (that is, those patients not eligible based on tumor size or grade). Cohort 1 will enroll approximately 3080 patients and Cohort 2 will enroll approximately 500 patients.

[0042] Patients in both treatment arms will receive standard adjuvant endocrine therapy of physician's choice (such as tamoxifen or an aromatase inhibitor, with or without ovarian function suppression per standard practice). Patients in both arms may have started standard adjuvant endocrine therapy within 8 weeks prior to randomization, and the same or another endocrine therapy will be continued during the course of the study and in the absence of disease recurrence. Consistent with standard guidelines, aromatase inhibitor should be at least part of endocrine therapy for postmenopausal patients. Adjuvant treatment with fulvestrant is not allowed at any time during the study. Randomization must occur no more than 12 weeks after completion of last non-endocrine therapy (surgery, or chemotherapy or radiotherapy). Patients randomized to the experimental arm will receive abemaciclib orally at 150 mg twice daily for up to 2 years or until evidence of disease recurrence or other discontinuation criteria are met, whichever occurs first. Endocrine therapy will be taken as prescribed during the on-study treatment period. (Years 1 and 2). In Year 3 and beyond, standard adjuvant endocrine therapy will continue to complete at least 5 years per investigator's discretion as part of standard of care.