In September, the FDA approved a third CDK4/6 inhibitor, abemaciclib (Verzenio), as monotherapy and in combination with fulvestrant for women with HR+/HER2- advanced or metastatic breast cancer with disease progression following endocrine therapy.
Favorable Adverse Event Profile
Overall, the MONALEESA-7 trial randomized 672 patients to ribociclib in combination with tamoxifen or an AI (letrozole or anastrozole) plus goserelin (n = 335) versus endocrine treatment alone in premenopausal or perimenopausal women with HR-positive/HER2-negative advanced breast cancer who had not previously received endocrine therapy for advanced disease.
The experimental regimen consisted of daily oral administration of ribociclib at 600 mg, tamoxifen at 20 mg, and either letrozole at 2.5 mg anastrozole at 1 mg plus a subcutaneous injection of goserelin at 3.6 mg once every 28 days. Ribociclib treatment was administered for 3 weeks followed by 1 week off.
Neutropenia remained the most frequently reported adverse event (AE) for both the experimental arm (76%) and the placebo arm (8%) in updated safety results. Six in 10 patients in the ribociclib arm experienced grade 3/4 neutropenia compared with 4% in the placebo arm, but the condition was asymptomatic in most patients. Two percent of patients in the experimental arm and 1% in the placebo arm experienced neutropenia associated with fever and infection.
Other AEs included hot flashes, nausea, leukopenia, and joint pain/stiffness. AEs leading to discontinuation of treatment occurred in 3.6% compared with 3.0% in patients who received endocrine therapy alone. The most common (≥5%) grade 3/4 AEs in patients receiving ribociclib combination therapy compared to endocrine therapy alone were neutropenia (60.6% vs 3.6%) and leukopenia (14.3% vs 1.2%)
Safety results were generally consistent with those observed in MONALEESA-2, which were identified early and mostly managed through dose interruptions or reductions. AEs resulted in discontinuation for 8.1% of those in the ribociclib arm versus 2.4% of those in the placebo group.
- Tripathy D, Sohn J, Im SA, et al. . GS2-05. First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: results from the randomized phase III MONALEESA-7 trial. Presented at: the 2017 San Antonio Breast Cancer Symposium; Dec. 5-9, 2017. Abstract GS2-05. www.abstracts2view.com/sabcs/view.php?nu=SABCS17L_828&terms=
- Hortobagyi GN, Stemmer SM, Burris HA, et al. Updated results from MONALEESA-2, a phase 3 trial of first-line ribociclib + letrozole in hormone receptor-positive (HR+), HER2-negative (HER2–), advanced breast cancer (ABC). J Clin Oncol. 2017;35(suppl; abstr 1038). meetinglibrary.asco.org/record/153081/abstract