MONARCH 3: Abemaciclib as initial therapy for advanced breast cancer

Matthew Philip Goetz, Masakazu Toi, Mario Campone, Olivier Trédan, Nawel Bourayou, Joohyuk Sohn, In Hae Park, Shani Paluch-Shimon, Jens Huober, Shin Cheh Chen, Luis Manso, Susana Barriga, Orit C. Freedman, Georgina Garnica Jaliffe, Tammy Forrester, Martin Frenzel, Ian C. Smith, Angelo Di Leo

Research output: Contribution to journalArticle

233 Citations (Scopus)

Abstract

Purpose Abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, demonstrated efficacy as monotherapy and in combination with fulvestrant in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with endocrine therapy. Methods MONARCH 3 is a double-blind, randomized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor in 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting. Patients received abemaciclib or placebo (150 mg twice daily continuous schedule) plus either 1 mg anastrozole or 2.5 mg letrozole, daily. The primary objective was investigator-assessed progression-free survival. Secondary objectives included response evaluation and safety. A planned interim analysis occurred after 189 events. Results Median progression-free survival was significantly prolonged in the abemaciclib arm (hazard ratio, 0.54; 95% CI, 0.41 to 0.72; P = .000021; median: not reached in the abemaciclib arm, 14.7 months in the placebo arm). In patients with measurable disease, the objective response rate was 59% in the abemaciclib arm and 44% in the placebo arm (P = .004). In the abemaciclib arm, diarrhea was the most frequent adverse effect (81.3%) but was mainly grade 1 (44.6%). Comparing abemaciclib and placebo, the most frequent grade 3 or 4 adverse events were neutropenia (21.1% v1.2%), diarrhea (9.5% v 1.2%), and leukopenia (7.6% v 0.6%). Conclusion Abemaciclib plus a nonsteroidal aromatase inhibitor was effective as initial therapy, significantly improving progression-free survival and objective response rate and demonstrating a tolerable safety profile in women with HR-positive, HER2-negative advanced breast cancer.

Original languageEnglish (US)
Pages (from-to)3638-3646
Number of pages9
JournalJournal of Clinical Oncology
Volume35
Issue number32
DOIs
StatePublished - Nov 10 2017

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Breast Neoplasms
Placebos
Disease-Free Survival
Aromatase Inhibitors
Therapeutics
letrozole
Hormones
Diarrhea
Cyclin-Dependent Kinase 6
Cyclin-Dependent Kinase 4
Safety
5-(4-ethylpiperazin-1-ylmethyl)pyridin-2-yl)-(5-fluoro-4-(7-fluoro-3-isopropyl-2-methyl-3H-benzimidazol-5-yl)pyrimidin-2-yl)amine
Leukopenia
Neutropenia
Appointments and Schedules
Research Personnel
human ERBB2 protein

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Goetz, M. P., Toi, M., Campone, M., Trédan, O., Bourayou, N., Sohn, J., ... Di Leo, A. (2017). MONARCH 3: Abemaciclib as initial therapy for advanced breast cancer. Journal of Clinical Oncology, 35(32), 3638-3646. https://doi.org/10.1200/JCO.2017.75.6155

MONARCH 3 : Abemaciclib as initial therapy for advanced breast cancer. / Goetz, Matthew Philip; Toi, Masakazu; Campone, Mario; Trédan, Olivier; Bourayou, Nawel; Sohn, Joohyuk; Park, In Hae; Paluch-Shimon, Shani; Huober, Jens; Chen, Shin Cheh; Manso, Luis; Barriga, Susana; Freedman, Orit C.; Jaliffe, Georgina Garnica; Forrester, Tammy; Frenzel, Martin; Smith, Ian C.; Di Leo, Angelo.

In: Journal of Clinical Oncology, Vol. 35, No. 32, 10.11.2017, p. 3638-3646.

Research output: Contribution to journalArticle

Goetz, MP, Toi, M, Campone, M, Trédan, O, Bourayou, N, Sohn, J, Park, IH, Paluch-Shimon, S, Huober, J, Chen, SC, Manso, L, Barriga, S, Freedman, OC, Jaliffe, GG, Forrester, T, Frenzel, M, Smith, IC & Di Leo, A 2017, 'MONARCH 3: Abemaciclib as initial therapy for advanced breast cancer', Journal of Clinical Oncology, vol. 35, no. 32, pp. 3638-3646. https://doi.org/10.1200/JCO.2017.75.6155
Goetz, Matthew Philip ; Toi, Masakazu ; Campone, Mario ; Trédan, Olivier ; Bourayou, Nawel ; Sohn, Joohyuk ; Park, In Hae ; Paluch-Shimon, Shani ; Huober, Jens ; Chen, Shin Cheh ; Manso, Luis ; Barriga, Susana ; Freedman, Orit C. ; Jaliffe, Georgina Garnica ; Forrester, Tammy ; Frenzel, Martin ; Smith, Ian C. ; Di Leo, Angelo. / MONARCH 3 : Abemaciclib as initial therapy for advanced breast cancer. In: Journal of Clinical Oncology. 2017 ; Vol. 35, No. 32. pp. 3638-3646.
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abstract = "Purpose Abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, demonstrated efficacy as monotherapy and in combination with fulvestrant in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with endocrine therapy. Methods MONARCH 3 is a double-blind, randomized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor in 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting. Patients received abemaciclib or placebo (150 mg twice daily continuous schedule) plus either 1 mg anastrozole or 2.5 mg letrozole, daily. The primary objective was investigator-assessed progression-free survival. Secondary objectives included response evaluation and safety. A planned interim analysis occurred after 189 events. Results Median progression-free survival was significantly prolonged in the abemaciclib arm (hazard ratio, 0.54; 95{\%} CI, 0.41 to 0.72; P = .000021; median: not reached in the abemaciclib arm, 14.7 months in the placebo arm). In patients with measurable disease, the objective response rate was 59{\%} in the abemaciclib arm and 44{\%} in the placebo arm (P = .004). In the abemaciclib arm, diarrhea was the most frequent adverse effect (81.3{\%}) but was mainly grade 1 (44.6{\%}). Comparing abemaciclib and placebo, the most frequent grade 3 or 4 adverse events were neutropenia (21.1{\%} v1.2{\%}), diarrhea (9.5{\%} v 1.2{\%}), and leukopenia (7.6{\%} v 0.6{\%}). Conclusion Abemaciclib plus a nonsteroidal aromatase inhibitor was effective as initial therapy, significantly improving progression-free survival and objective response rate and demonstrating a tolerable safety profile in women with HR-positive, HER2-negative advanced breast cancer.",
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T2 - Abemaciclib as initial therapy for advanced breast cancer

AU - Goetz, Matthew Philip

AU - Toi, Masakazu

AU - Campone, Mario

AU - Trédan, Olivier

AU - Bourayou, Nawel

AU - Sohn, Joohyuk

AU - Park, In Hae

AU - Paluch-Shimon, Shani

AU - Huober, Jens

AU - Chen, Shin Cheh

AU - Manso, Luis

AU - Barriga, Susana

AU - Freedman, Orit C.

AU - Jaliffe, Georgina Garnica

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N2 - Purpose Abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, demonstrated efficacy as monotherapy and in combination with fulvestrant in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with endocrine therapy. Methods MONARCH 3 is a double-blind, randomized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor in 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting. Patients received abemaciclib or placebo (150 mg twice daily continuous schedule) plus either 1 mg anastrozole or 2.5 mg letrozole, daily. The primary objective was investigator-assessed progression-free survival. Secondary objectives included response evaluation and safety. A planned interim analysis occurred after 189 events. Results Median progression-free survival was significantly prolonged in the abemaciclib arm (hazard ratio, 0.54; 95% CI, 0.41 to 0.72; P = .000021; median: not reached in the abemaciclib arm, 14.7 months in the placebo arm). In patients with measurable disease, the objective response rate was 59% in the abemaciclib arm and 44% in the placebo arm (P = .004). In the abemaciclib arm, diarrhea was the most frequent adverse effect (81.3%) but was mainly grade 1 (44.6%). Comparing abemaciclib and placebo, the most frequent grade 3 or 4 adverse events were neutropenia (21.1% v1.2%), diarrhea (9.5% v 1.2%), and leukopenia (7.6% v 0.6%). Conclusion Abemaciclib plus a nonsteroidal aromatase inhibitor was effective as initial therapy, significantly improving progression-free survival and objective response rate and demonstrating a tolerable safety profile in women with HR-positive, HER2-negative advanced breast cancer.

AB - Purpose Abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, demonstrated efficacy as monotherapy and in combination with fulvestrant in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with endocrine therapy. Methods MONARCH 3 is a double-blind, randomized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor in 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting. Patients received abemaciclib or placebo (150 mg twice daily continuous schedule) plus either 1 mg anastrozole or 2.5 mg letrozole, daily. The primary objective was investigator-assessed progression-free survival. Secondary objectives included response evaluation and safety. A planned interim analysis occurred after 189 events. Results Median progression-free survival was significantly prolonged in the abemaciclib arm (hazard ratio, 0.54; 95% CI, 0.41 to 0.72; P = .000021; median: not reached in the abemaciclib arm, 14.7 months in the placebo arm). In patients with measurable disease, the objective response rate was 59% in the abemaciclib arm and 44% in the placebo arm (P = .004). In the abemaciclib arm, diarrhea was the most frequent adverse effect (81.3%) but was mainly grade 1 (44.6%). Comparing abemaciclib and placebo, the most frequent grade 3 or 4 adverse events were neutropenia (21.1% v1.2%), diarrhea (9.5% v 1.2%), and leukopenia (7.6% v 0.6%). Conclusion Abemaciclib plus a nonsteroidal aromatase inhibitor was effective as initial therapy, significantly improving progression-free survival and objective response rate and demonstrating a tolerable safety profile in women with HR-positive, HER2-negative advanced breast cancer.

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