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MONARCH 3 was a randomized, double-blind, placebo-controlled, phase 3 study of abemaciclib or placebo with an NSAI (anastrozole or letrozole) in 493 postmenopausal women with HR+, HER2- advanced or MBC with no prior systemic treatment in this setting.1
Endocrine therapy in the neoadjuvant or adjuvant setting was permitted if patients had a disease free interval of >12 months since completion of ET.1
Patients were randomized 2:1 to abemaciclib or placebo in combination with an NSAI.
Abemaciclib 150 mg or matching placebo was administered orally twice daily on a continuous schedule.
Anastrozole 1 mg or letrozole 2.5 mg (per physician’s choice) was administered orally once daily on a continuous schedule.1
Patients were stratified according to metastatic site (visceral, bone-only, vs other) and prior (neo)adjuvant ET (aromatase inhibitor, no ET, vs other). The primary endpoint was investigator-assessed PFS and key secondary endpoints included OS, response rates, and safety.1
Progression-free survival was evaluated according to RECIST version 1.1. At the time of the final PFS analysis, median follow-up was 26.7 months and OS data were immature.2 Median relative dose intensity was 85% for abemaciclib and 98% for placebo.1
Efficacy analyses are presented in Table 1. Primary and Select Secondary Efficacy Endpoints in MONARCH 3 .
Table 1. Primary and Select Secondary Efficacy Endpoints in MONARCH 32
Abbreviations: ITT = intent-to-treat; NSAI = nonsteroidal aromatase inhibitor.
b Responder population.
c Objective response rate = complete response + partial response.
d Clinical benefit rate = complete response + partial response + stable disease ≥6 months.
e Confirmed objective response rate = 55.4%.
f Confirmed objective response rate = 40.2%.
A blinded independent central review was conducted and confirmed ITT PFS benefit (HR=0.465; 95% CI: 0.339-0.636; p<.000001).2
Abemaciclib plus an NSAI demonstrated improved PFS across all patient subgroups analyzed.1-3
While all subpopulations benefited from the addition of abemaciclib to ET regardless of prognosis, in a subgroup analysis of patients in MONARCH 2 and MONARCH 3, substantial benefit of abemaciclib (characterized by large increases in PFS [HRs=0.4-0.5] and ORR [>30%]) was observed in poor prognosis subgroups with liver metastases, progesterone receptor-negative tumors, and high-grade tumors.3
A subpopulation treatment effect pattern plot analysis of TFI of the MONARCH 3 patients who had received adjuvant ET demonstrated that patients who had a shorter TFI had a worse prognosis and received relatively greater benefit from abemaciclib plus NSAI than did patients with a longer TFI. Patients with bone-only disease or a longer TFI also received benefit from abemaciclib, but to a relatively lesser extent (HR ranging from approximately 0.6-0.8).3
Table 2. Adverse Reactions in the MONARCH 3 Safety Population (abemaciclib+NSAI, n=327; placebo+NSAI, n=161)4
Abbreviation: NSAI = nonsteroidal aromatase inhibitor.
In the abemaciclib arm, 13% of patients permanently discontinued treatment and dose reductions occurred in 43% of patients due to adverse reactions.5
Deaths due to AEs were reported in 11 patients in the abemaciclib arm and included
lung infection (n=4)
respiratory failure (n=2)
cerebral ischemia (n=1)
cerebrovascular accident (n=1), and
Deaths due to AEs were reported in 2 patients in the placebo arm and included
Abemaciclib plus NSAI significantly improved PFS and ORR as initial therapy for HR+, HER2- postmenopausal advanced breast cancer patients compared with NSAI alone. Abemaciclib was generally well tolerated.1,2
1. Goetz MP, Toi M, Campone M, et al. MONARCH 3: Abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017;35(32):3638-3646. https://doi.org/10.1200/jco.2017.75.6155.
2. Goetz MP, Martin M, Di Leo A, et al. MONARCH 3: Abemaciclib as initial therapy for patients with HR+, HER2- advanced breast cancer – Results from the preplanned final PFS analysis. Presented as an oral presentation at: 109th Annual Meeting of the American Association for Cancer Research (AACR); April 14-18, 2018; Chicago, IL. http://www.abstractsonline.com/pp8/#!/4562/presentation/11141.
3. Di Leo A, O'Shaughnessy J, Sledge GW, et al. Prognostic characteristics in hormone receptor-positive advanced breast cancer and characterization of abemaciclib efficacy [published online December 18, 2018]. NPJ Breast Cancer. 2018;4(1):41. http://dx.doi.org/10.1038/s41523-018-0094-2
AE = adverse event
ALT = alanine aminotransferase
ET = endocrine therapy
HER2- = human epidermal growth factor receptor 2-negative
HR = hazard ratio
HR+ = hormone receptor-positive
ITT = intent-to-treat
MBC = metastatic breast cancer
NSAI = nonsteroidal aromatase inhibitor
ORR = overall response rate
OS = overall survival
PFS = progression-free survival
RECIST = Response Evaluation Criteria in Solid Tumors
TFI = treatment-free interval
▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.
Datum fӧr senaste ӧversyn 2019 M02 04