Ribociclib plus endocrine therapy improves survival in advanced breast cancer subtype
CHICAGO — Premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer derived a significant survival benefit from the addition of ribociclib to endocrine therapy, according to the most recent OS results from the randomized phase 3 MONALEESA-7 study presented at ASCO Annual Meeting.
“This study is unique because it’s the only trial that exclusively enrolled young women — pre- or perimenopausal women younger than 59 [years],” lead author Sara A. Hurvitz, MD, director of the breast cancer clinical research program at UCLA Jonsson Comprehensive Cancer Center, said in an interview with HemOnc Today. “We wanted to do this study because young women represent about 20% of all breast cancers in women younger than 50 [years]. They have worse survival and more aggressive disease biology compared with older women.”
Ribociclib (Kisqali, Novartis), a CDK4/6 inhibitor, received FDA approval in July 2018 for use with an aromatase inhibitor by pre- or perimenopausal women with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer. This approval was based on earlier results from the randomized, double-blind MONALEESA-7 trial, which enrolled 672 premenopausal women with this form of advanced breast cancer who received goserelin (Zoladex; TerSera AstraZeneca) with ribociclib (n = 335) or placebo (n = 337). All women also received a nonsteroidal aromatase inhibitor (letrozole or anastrozole) or tamoxifen.
The analysis is the second of three protocol-specific analyses of OS scheduled to occur after approximately 189 deaths (75% of planned total events). The prespecified interim analysis had a data cutoff of Nov. 30, 2018, with a median follow-up of 34.6 months (minimum, 28 months).
At data cutoff, 173 patients remained on treatment (ribociclib, n = 116 [35%]; placebo, n = 57 [17%]). Researchers assessed OS after 192 deaths (ribociclib, n = 83; placebo, n = 109).
Results showed significantly longer median OS with ribociclib and endocrine therapy vs. placebo and endocrine therapy (not reached vs. 40.9 months, HR = 0.71; 95% CI, 0.53-0.94), representing a 29% relative reduction in risk for death. This crossed the prespecified stopping boundary for superior efficacy
OS rate with ribociclib and endocrine therapy was 70.2% vs. 46% with placebo and endocrine therapy.
Among women treated with a nonsteroidal aromatase inhibitor, researchers observed sustained OS improvement in the ribociclib vs. placebo group (not reached vs. 40.7 months; HR = 0.69; 95% CI, 0.5-0.98). The two groups demonstrated similar rates of post-treatment therapy use (68.9% vs. 73.2%).
Among women treated with tamoxifen, median OS was not reached for those who also received ribociclib or placebo (HR = 0.79; 95% CI, 0.45-1.37).
Researchers are analyzing patient-reported outcomes as well as biomarkers and circulating tumor DNA to identify which women could benefit most from ribociclib.
“The impact of these findings will likely be large, because hormone receptor breast cancer comprises two-thirds of all breast cancers diagnosed,” Hurwitz told HemOnc Today. “This is not a small subset of patients. We do have three drugs approved in this indication, and the MONALEESA-7 study is the first study to show a significant improvement in OS.” – by Jennifer Byrne
Hurvitz S, et al. Abstract LBA1008. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.
Disclosures: The study received funding from Novartis. Hurvitz reports travel accommodations and expenses from Eli Lilly, Novartis and OBI Pharma; and research funding to her institution from Amgen, Ambryx, Bayer, Biomarin, Boehringer Ingelheim, Cascadian Therapeutics, Daiichi Sankyo, Dignitana Genentech/Roche, GlaxoSmithKline, Eli Lilly, Macrogenics, Medivation, Merrimack, Novartis, OBI Pharma, Pfizer, Puma Biotechnology and Seattle Genetics. Please see the abstract for all other authors’ relevant financial disclosures.