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CHICAGO -- Adding ribociclib (Kisqali) to endocrine therapy significantly prolonged survival in women with advanced HR-positive/HER-negative breast cancer, with a 29% lower risk of death, a researcher reported here.

In the MONALEESA 7 trial, the estimated overall survival (OS) at 42 months was 70.2% (95% 63.5-76.0) in the ribociclib group versus 46.0% (95% CI 32.0-58.9) in the placebo group, for a hazard ratio for death of 0.71 (95% CI 0.54-0.95, P=0.00973 by log-rank test), reported Sara Hurvitz, MD, of the University of California Los Angeles, at the American Society of Clinical Oncology (ASCO) annual meeting. The results will be published in the .

"This is the first study to demonstrate improved survival for a targeted therapy," Hurvitz said at an ASCO press conference.

Hurvitz told 口袋女优 that the patient population was particularly unique because all were premenopausal, younger women (ages <59). She added that "We saw no new safety signals ... Women feel well while on this therapy, they can raise their children, work on their career, be functional, and feel good while they are receiving therapy that we have now shown extends how long they will live."

Progression-free survival (PFS) results from MONALEESA 7 were presented at the 2018 and published in the . Ribociclib was associated with about a 10-month median PFS advantage versus placebo.

"Overall survival benefit is considered the 'gold standard' in cancer trials but is challenging to achieve in HR+/HER2- metastatic breast cancer. MONALEESA-7 reached this important endpoint earlier than anticipated," Hurvitz said in a . "Impactful results like these ribociclib findings are what we wish for in every clinical trial, and to achieve overall survival improvement in an incurable disease, like metastatic breast cancer, is truly an outstanding advancement for patients."

Based on the 2018 PFS results, the FDA for the CDK 4/6 inhibitor in combination with an aromatase inhibitor (AI) for pre- or perimenopausal women with HR+/HER2-advanced or metastatic breast cancer, as initial endocrine-based therapy. Ribociclib also was approved in combination with fulvestrant for postmenopausal women with HR+/HER2- advanced or metastatic breast cancer, as initial endocrine-based therapy or following disease progression on endocrine therapy.

Patients were assigned to either ribociclib or placebo in addition to endocrine therapy, specifically goserelin and either a nonsteroidal AI or tamoxifen. A total of 672 patients were included in the intention-to-treat (ITT) population. There were 83 deaths among 335 patients (24.8%) in the ribociclib group and 109 deaths in 337 patients (32.3%) in the placebo group.

The authors also reported that the survival benefit seen in the subgroup of 495 patients who received an AI was consistent with that in the overall ITT population (HR 0.70 for death, 95% CI 0.50 to 0.98). Also, 68.9% in the ribociclib group and 73.2% in the placebo group received subsequent antineoplastic therapy

Patients in the study arm also saw a longer time from randomization to disease progression during receipt of second-line therapy or to death versus the placebo patients (HR 0.69 for disease progression or death, 95% CI 0.55- 0.87).

Key grade 3/4 adverse events were:

• Neutropenia: 63.5% of patients in the ribociclib group; 4.5% in the placebo group
• Hepatobiliary toxic effects: 11%; 6.8%
• Prolonged QT interval: 1.8%; 1.2%

Hurvitz and colleagues noted that more instances of QT-interval prolongation were seen in patients who received the study drug, or placebo, and tamoxifen versus those who received ribociclib and an AI.

"I think one of the great things about these data is that it may improve access worldwide where OS needs to be demonstrated in order for governments and institutions to provide this type of drug to patients," Hurvitz said.

ASCO spokesperson Harold Burstein, MD, PhD, of the Dana-Farber Cancer Institute in Boston, noted that "this is an important study because it shows that the class of drugs of CDK4/6 inhibitors -- which we are widely using and have been shown to delay the time-to-treatment progression -- delay the time for the need for chemotherapy in breast cancer, and really doubled the effectiveness of endocrine therapy, [and] now also translates into a significant survival benefit for women who have estrogen-receptor positive breast cancer."

Burstein agreed that the younger patient population in MONALEESA 7 was important; other trials using CDK 4/6 inhibitors, such as PALOMA-3, included women who were premenopausal and postmenopausal, and were more heavily pretreated.

"Young women are often thought to have different types of breast cancer, such as triple negative breast cancer, [but] in fact, estrogen-positive breast cancer is the most common type of breast cancer in younger women," he told 口袋女优.

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