Abstract
Adding the CDK4/6 inhibitor ribociclib to standard first-line endocrine therapy significantly prolonged survival in premenopausal and perimenopausal women with advanced HR-positive, HER2-negative breast cancer enrolled in the MONALEESA-7 trial. This is the first definitive evidence that CDK4/6 inhibitor–based therapy is effective for first-line treatment of premenopausal and perimenopausal women.
Adding the CDK4/6 inhibitor ribociclib (Kisqali; Novartis) to standard first-line endocrine therapy significantly prolonged survival in premenopausal and perimenopausal women with advanced HR-positive, HER2-negative breast cancer. These findings, from the MONALEESA-7 trial, were presented during the 2017 San Antonio Breast Cancer Symposium, held December 5–9 in Texas. This is the first definitive evidence that CDK4/6 inhibitor–based therapy is effective for premenopausal and perimenopausal women, who account for about 20% of breast cancer diagnoses in the United States.
In the trial, 672 premenopausal and perimenopausal women with HR-positive, HER2-negative breast cancer were randomized to receive ribociclib or placebo combined with either tamoxifen or a nonsteroidal aromatase inhibitor (letrozole or anastrozole), plus goserelin to suppress estrogen production. Median progression-free survival (PFS) was significantly longer in the ribociclib groups compared with the placebo groups (23.8 versus 13 months), and the overall response rate in patients with measurable disease was 50.9% and 36.4%, respectively.
“There's a clear unmet need for treatment in pre- and perimenopausal patients with HR-positive, HER2-negative advanced breast cancer,” said the study's lead investigator, Debu Tripathy, MD, professor of medicine and chair of Breast Medical Oncology at The University of Texas MD Anderson Cancer Center in Houston, who presented the findings. “This is the first study to clearly show that a CDK4/6 inhibitor–based regimen is beneficial for younger women, who tend to have a distinct tumor biology and may experience higher risk of progression and death.”
Ribociclib plus endocrine therapy is already approved for first-line treatment of postmenopausal patients with HR-positive, HER2-negative disease, based on data from the MONALEESA-2 trial. Findings from MONALEESA-7 have been submitted to the FDA, which is expected to update the drug's indication to include premenopausal and perimenopausal women, said Tripathy.
In MONALEESA-7, the median PFS was lower in patients who took ribociclib with tamoxifen versus ribociclib with an aromatase inhibitor (22.1 versus 27.5 months). However, the findings do not necessarily mean that one form of endocrine therapy is preferable to another, said Tripathy. For example, tamoxifen might be preferred for a patient who previously experienced side effects or tumor progression on an aromatase inhibitor, or vice versa.
Patients taking ribociclib were more likely to experience certain serious adverse events, including neutropenia (61% vs. 4%) and leukopenia (14% vs. 1%), although neutropenia was asymptomatic in most patients. Adverse events led to discontinuation of treatment in 4% of patients in the ribociclib arms versus 3% in the control arms.
With convincing data on the use of ribociclib regardless of menopausal status, CDK4/6-based therapy is likely to replace standard chemotherapy for metastatic disease, said Tripathy. Studies are now testing the use of CDK4/6 inhibitors, including palbociclib (Ibrance; Pfizer), following initial therapy.
“In the second-line setting, the MONALEESA-3 trial is investigating the effectiveness of fulvestrant plus or minus ribociclib, and the [PALOMA-3] trial is investigating palbociclib with fulvestrant,” he said. “There are indications for the use of CDK4/6 inhibitors in all lines of therapy.” –Janet Colwell
