Abemaciclib: MONARCH 1 - Uso de agente único en Cáncer de Mama Metastásico

Detailed Information

MONARCH 1 was a phase 2, single-arm study which evaluated safety and efficacy of abemaciclib as monotherapy in 132 women with refractory HR+, HER2- advanced or MBC whose disease progressed on or after both ET and chemotherapy.¹ 

Abemaciclib 200 mg was administered orally every 12 hours on a continuous schedule (days 1-28 of a 28-day cycle) until disease progression or unacceptable toxicity. The primary objective of MONARCH 1 was to evaluate investigator-assessed ORR performed at 12 months after the last patient had entered treatment.¹

A total of 132 women were treated with abemaciclib monotherapy. All patients had a median of 5 lines of prior therapy for any setting, including a median of 3 lines of prior therapy for metastatic disease.² Prior therapies in the metastatic setting included

• ET (87.1%)

• fulvestrant (50.8%)

• taxane (68.9%)

• everolimus (28.0%), and

• capecitabine (55.3%).^1,3

In the MONARCH 1 trial, exposure measurements included 

• patients who received ≥8 cycles of therapy (35.6%)

• median dose compliance (99%), and

• median relative dose intensity (89.2%).^1,2,4

The 12-month primary analysis is presented in Table 1.

Table 1. MONARCH 1 Primary 12-Month Efficacy Analysis Results¹

Abbreviations: CR = complete response; PR = partial response; SD = stable disease.

The most common adverse reactions, occurring in ≥20% of patients were

• diarrhea

• fatigue

• nausea

• abdominal pain

• infections

• decreased appetite

• vomiting

• neutropenia

• anemia

• thrombocytopenia, and

• headache.⁵

Dose reductions due to adverse reactions were reported in 49% of patients. Overall, discontinuation of abemaciclib due to adverse reactions was 8%.⁴

Diarrhea was reported in 90.2% of patients overall (median onset of 7 days) as

• grade 2: 28.8% of patients

• grade 3: 19.7% of patients, and

• grade 4: no patients.

One patient discontinued treatment due to diarrhea. The majority of patients responded to management with over the counter antidiarrheal medications and dose alterations.¹

Neutropenia as an AR was observed in 37.1% of patients overall as

• grade 3: 18.9% of patients, and

• grade 4: 5.3% of patients.

One patient experienced febrile neutropenia which occurred during the study follow-up period (19 days after discontinuation of abemaciclib) and 8 days after the patient began cytotoxic chemotherapy (fluorouracil and vinorelbine).¹

Creatinine laboratory values were increased in 98.5% of patients.¹

Abemaciclib has been shown to increase serum creatinine due to inhibition of renal tubular secretion transporters without affecting glomerular function.⁴

References

1. Dickler MN, Tolaney SM, Rugo HS, et al. MONARCH 1, a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as a single agent, in patients with refractory HR+/HER2- metastatic breast cancer [published correction appears in Clin Cancer Res. 2018;24(21):5475. http://clincancerres.aacrjournals.org/content/24/21/5485.article-info ]. Clin Cancer Res. 2017;23(17):5218-5224. http://dx.doi.org/10.1158/1078-0432.CCR-17-0754

2. Dickler MN, Tolaney SM, Rugo HS, et al. MONARCH 1: results from a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as monotherapy, in patients with HR+/HER2- breast cancer, after chemotherapy for advanced disease. Presented as an oral presentation at: 52nd Annual Meeting of the American Society of Clinical Oncology (ASCO); June 03-07, 2016; Chicago, IL. http://abstract.asco.org/176/AbstView_176_164546.html

3. Rugo HS, Tolaney SM, Cortés J, et al. MONARCH 1: Final overall survival analysis of a phase 2 study of abemaciclib, a CDK4 and CDK6 inhibitor, as monotherapy, in patients with HR+/HER2- breast cancer, after chemotherapy for advanced disease. Talk presented at: 108th Annual Meeting of the American Association for Cancer Research (AACR); April 1-5, 2017; Washington, DC. http://webcast.aacr.org/s/2017annual/CTSY03;jsessionid=37972ACCE273164EDABF5110831422D6.

4. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

5. Verzenio [package insert]. Indianapolis, IN: Eli Lilly and Company; 2019.

Glossary

AR = adverse reaction

ET = endocrine therapy

HER2- = human epidermal growth factor receptor 2-negative

HR+ = hormone receptor-positive

MBC = metastatic breast cancer

ORR = objective response rate