The international, randomized phase III MONALEESA-7 trial found that the addition of ribociclib to standard-of-care endocrine therapy significantly improved overall survival for premenopausal women with advanced hormone receptor (HR)-positive, HER2-negative breast cancer compared with endocrine therapy alone. After 42 months of follow-up, the survival rate was 70% for women treated with the combination therapy compared with 46% for women who received endocrine therapy alone. The study was presented by Hurvitz et al at the 2019 ASCO Annual Meeting (Abstract LBA1008).
“This is the first study to show improved survival for any targeted therapy when used with endocrine therapy as a first-line treatment for advanced breast cancer,” said lead study author Sara A. Hurvitz, MD, Director of the Breast Cancer Clinical Research Program at the University of California, Los Angeles Jonsson Comprehensive Cancer Center.
Advanced breast cancer is less common in premenopausal women than in older women, and the incidence is increasing. In the United States, in women aged 20 to 39, the incidence of advanced breast cancer increased 2% per year between 1978 and 2008, according to a report by Johnson et al in JAMA. In July 2018, the U.S. Food and Drug Administration approved the expanded indication for ribociclib in combination with an aromatase inhibitor to include pre- and perimenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer.
MONALEESA-7 is the first trial to focus exclusively on women younger than age 59 who were premenopausal and had advanced breast cancer for which they had not received prior endocrine therapy.
Investigators randomly assigned women to receive treatment with oral ribociclib or a placebo. All women enrolled also received goserelin, as injectable endocrine therapy, and one of three other therapies: the nonsteroidal aromatase inhibitors letrozole or anastrozole, or tamoxifen.
A total of 672 women were enrolled in the study. After a median follow-up of 34.6 months, 173 (26%) were still on treatment, with 116 (35%) of the women still receiving ribociclib and 57 (17%) still receiving placebo. Overall survival was evaluated after 192 deaths (83 in the ribociclib arm, 109 in the placebo arm).
The women who received ribociclib had a progression-free survival of 23.8 months vs 13 months for women who received the placebo. The researchers observed that after 42 months of follow-up, for patients receiving ribociclib, the survival rate was 70% when given with endocrine therapy, compared with 46% when given with placebo. Overall, this represented a 29% relative reduction in the risk of death.
In addition, the survival rate was 71% and 70% for women who took ribociclib in combination with tamoxifen or a nonsteroidal aromatase inhibitor, respectively, compared with a survival rate of 55% and 43%, respectively, for women who received placebo in combination with tamoxifen or aromatase inhibitors alone. Posttreatment therapy use was balanced between treatment arms—68.9% in the ribociclib arm and 73.2% in the placebo arm.
The researchers are doing analyses of patient-reported outcomes, as well as subanalyses of the clinical findings, including looking at biomarkers and circulating tumor DNA that may help them determine which women might benefit most from ribociclib. The investigators are also studying the use of ribociclib in women and men with early-stage HR-positive, HER2-negative breast cancer in combination with endocrine therapy and other cancer indications.
Disclosure: This study received funding from Novartis. For full disclosures of the study authors, visit coi.asco.org.
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