Although nearly 20% of invasive breast cancer is diagnosed in women under the age of 50 years, the majority of clinical trials are limited to postmenopausal patients. Furthermore, younger patients are typically burdened with more aggressive disease and poorer survival compared to older, postmenopausal patients, making this an important area of unmet need. The cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor ribociclib is currently approved for the treatment of postmenopausal women with hormone receptor (HR)-positive, HER2-negative advanced breast cancer, and the ongoing, randomized phase III MONALESSA-7 study is examining the addition of ribociclib to first-line endocrine therapy in pre/perimenopausal patients with HR-positive, HER2-negative advanced breast cancer.
At the 2017 San Antonio Breast Cancer Symposium (SABCS), Debu Tripathy, MD (The University of Texas MD Anderson Cancer Center, Houston, Texas, United States), presented results from this important study. Patients (N = 672) received standard hormonal therapy (either tamoxifen or a nonsteroidal aromatase inhibitor [NSAI]) and the LHRH agonist goserelin with either ribociclib or placebo.
At a median follow-up of 19.2 months, the addition of ribociclib to standard hormonal therapy in pre/peri-menopausal patients with breast cancer resulted in nearly 11-month improvement in progression-free survival (23.8 months vs 13.0 months; HR 0.553, P<.0001). PFS favored ribociclib across all patient subgroups. Best outcomes were seen when ribociclib was combined with an NSAI (27.5 months) rather than with tamoxifen (22.1 months). The clinical benefit rate was 79.9% for ribociclib plus hormonal therapy, compared to 67.3% for placebo plus hormonal therapy (P = .00034). Overall survival data are not yet mature and were not included in this analysis.
The adverse event (AE) profile was consistent with that seen in other trials of ribociclib. Any grade hematologic AEs occurred more frequently in patients treated with ribociclib compared with placebo, including neutropenia (75.8% vs 7.7%), leukopenia (31.3% vs 5.6%), anemia (20.9% vs 10.1%), and thrombocytopenia (8.7% vs 2.1%). Rates of non-hematologic AEs were similar between the two treatment groups, with the exception of nausea, which occurred more frequently in patients treated with ribociclib (21.6% vs 19.6%). More patients receiving ribociclib required dose interruptions or reductions. Despite the increase in AEs seen with ribociclib, patients in the ribociclib arm reported greater improvements in health-related quality of life compared to the placebo arm.
Dr Tripathy concluded that these results support the addition of ribociclib as a treatment option for premenopausal women with HR-positive, HER2-negative advanced breast cancer. Additionally, the similarity between these results and those seen with ribociclib in postmenopausal patients provides support that treatment options for postmenopausal patients may be effective options for premenopausal patients.
For additional practice-changing developments in the management of advanced ER-positive breast cancer presented at 2017 SABCS, please see prIME Oncology’s recent Clinical Spotlight. Also view an expert discussion of clinical vignettes to increase your knowledge of using CDK 4/6 inhibitors in clinical practice.