This article is more than 5 years old. Information may no longer be current.
Ribociclib improves PFS in younger women with advanced breast cancer
Click Here to Manage Email Alerts
SAN ANTONIO — The addition of ribociclib to standard endocrine therapy with temporary ovarian suppression significantly improved PFS in pre- and perimenopausal women with hormone receptor-positive, HER-2-negative advanced breast cancer, according to results of the phase 3 MONALEESA-7 trial presented at the San Antonio Breast Cancer Symposium.
“There is a clear unmet need for a treatment for patients with HER-2-negative advanced breast cancer, which accounts for about 20% of patients diagnosed in the United States,” Debu Tripathy, MD, professor of medicine and chair of the department of breast medical oncology at The University of Texas MD Anderson Cancer Center, and a HemOnc Today Editorial Board Member, said during a press briefing.
“Younger women tend to have a distinct biology with more aggressive features and may actually experience a higher risk for progression and death,” Tripathy added. “The endocrine therapy typically recommended involves ovarian suppression, but ultimately resistance develops in virtually all cases and prior to MONALEESA-7, there have not been large-scale phase 3 studies for pre/perimenopausal patients.”
Three CDK4/6 inhibitors have been approved by the FDA, including ribociclib (Kisqali, Novartis).
Between December 2014 and August 2016, Tripathy and colleagues randomly assigned 672 women to receive oral hormonal therapy — tamoxifen, or nonsteroidal aromatase inhibitors letrozole or anastrozole — and goserelin (Zoladex; TerSera Therapeutics, AstraZeneca) with ribociclib (n = 335; median age, 43 years) or placebo (n = 337; median age, 45 years).
PFS served as the study’s primary outcome; the secondary outcome was ORR.
Results showed a median PFS of 23.8 months among women assigned ribociclib vs. 13 months among those assigned placebo (HR = 0.55; 95% CI, 0.44-0.69).
PFS improved among patients assigned ribociclib regardless of whether they received tamoxifen (22.1 months vs. 11 months; HR = 0.58; 95% CI, 0.28-0.88) or letrozole or anastrozole (27.5 months vs. 13.8 months; HR = 0.56; 95% CI, 0.43-0.74).
ORR appeared higher among patients assigned ribociclib in the total study population (40.9% vs. 29.7%) and among patients with measurable disease at baseline (50.9% vs. 36.4%).
The most frequent adverse event was neutropenia, occurring among 76% of patients in the ribociclib arm vs. 8% in the placebo arm. Although asymptomatic in most patients, grade 3 to grade 4 neutropenia occurred among 61% of patients in the ribociclib arm vs. 4% in the placebo arm.
Adverse events including, hot flashes, nausea, leukopenia and joint pain/stiffness, led to treatment discontinuation among 4% of patients in the ribociclib arm and 3% of patients in the placebo arm.
“The clinical implications of these findings are that CDK4/6 inhibition, which we know is effective in postmenopausal women when added to hormonal therapy, is effective in pre- and perimenopausal patients as long as they have ovarian suppression — which we did not know before this trial,” Tripathy told HemOnc Today. “More importantly, we showed that ribociclib was effective with either hormonal therapy that we would typically use in this situation.”
OS data are not yet mature and will be presented in the future, Tripathy said. – by Jennifer Southall
Reference:
Tripathy D, et al. Abstract GS2-05. Presented at: San Antonio Breast Cancer Symposium; Dec. 5-9, 2017; San Antonio.
Disclosures: Tripathy reports a paid consultant with Novartis. The University of Texas MD Anderson Cancer Center received funding from Novartis to conduct the study. Please see the abstract for a full list of all other authors’ relevant financial disclosures.