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Singleagent activity with a CDK and inhibitor represents a major advance in therapy of treatmentrefractory HR HER MBC, and targeted agents such as abemaciclib may be the next generation of agents for this otherwise poor prognosis patient population.In a phase I study, administration of abemaciclib as a single agent on a continuous schedule was feasible with grade fatigue as the doselimiting toxicity. In that phase I study, abemaciclib as a single agent demonstrated antitumor activity in patients with several cancers with an ORR of in patients with hormone refractory HR MBC. On the basis of the singleagent activity observed in this population, the current phase II MONARCH study was launched.MONARCH is a multicenter, singlearm, openlabel study to evaluate the singleagent activity of abemaciclib and further characterize the adverse event prole in patients with HR HER MBC who have received cytotoxic chemotherapy for MBC.This is a population for whom endocrine therapy would no longer be considered suitable.Patients were enrolled at sites in four countries. The primary objective was to evaluate ORR based on investigatorassessed tumor response according to RECIST v.A secondary analysis using independently reviewed tumor response was also planned.Patients were followed until death or overall study completion at months after the last patient was enrolled.Patients on study therapy who continued to experience clinical benet after study completion could continue to receive study therapy until one of the criteria for discontinuation was met.Key exclusion criteria included prior treatment with CDK and CDK inhibitors; major surgery within days; treatment with an investigational agent within or days of initial dose of study drug for nonmyelosuppressive or myelosuppressive agents, respectively; evidence or history of central nervous system metastases; and history of any other cancer, unless in complete remission with no therapy for years.All tumor measurement images for all enrolled patients were collected to allow for an independent review.OS was measured from the date of rst dose of study drug to the date of death from any cause.OS was censored at the date of last contact prior to the data inclusion cutoff date.Patients were followed for OS for months following the last patient entering treatment.The null hypothesis of was chosen on the basis of historical data as an ORR representative of what might be expected for approved chemotherapies that may be used in this taxanerefractory setting. Point estimates and exact CI for DCR and CBR were calculated.Assessments by independent review yielded comparable rates and estimates. As indicated in the protocol, many patients received loperamide.Time on treatment with abemaciclib is plotted for each patient treated in the MONARCH study. Increases in blood urea nitrogen were not observed. Decreases in neutrophil counts were observed in patients; the majority of patients had a grade or decrease, with. of patients with a grade event. Neutrophil counts typically reached nadir between and weeks after the start of treatment, and remained depressed and stable throughout the dosing period. Less than of patients received hematopoietic Thujone growth factor support. One patient experienced febrile neutropenia; this occurred during the study followup period and days after the patient began cytotoxic chemotherapy experienced an infection, the majority of which were lowgrade; there did not appear to be a relationship between the occurrence of severe neutropenia and the occurrence of infection.

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