Spectacular increase of bone with Kisqali in young breast cancer patients

CHICAGO – The addition of ribociclib (Kisqali) to endocrine therapy has significantly prolonged the survival of women with advanced breast cancer at HR positive / HER, with a 29% reduced risk of death , reported a researcher.

In the MONALEESA 7 trial, the overall survival estimated 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 risk ratio for a death of 0.71 (95% CI: 0.54-0.95, PSara Hurvitz, MD, of the University of California at Los Angeles, at the annual meeting of the American Society of Clinical Oncology (ASCO). The results will be published in New England Journal of Medicine.

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

Hurvitz said MedPage today that the patient population was particularly unique because all were younger and non-menopausal women (under 59 years of age). She added, "We have not seen any new safety signals … Women feel good during this therapy, they can raise their children, work their careers, be functional and feel good while they are not in bed. they are following a therapy that we have now shown they will live. "

MONALEESA 7 results for progression-free survival (PFS) were presented at the 2018 San Antonio Breast Cancer Symposium and published Oncology Lancet. Ribociclib was associated with a median median progression-free survival advantage of approximately 10 months compared with placebo.

"The overall benefit in terms of survival is considered the" standard of reference "in cancer trials, but it is difficult to achieve for HR + / HER2 metastatic breast cancer.MONALEESA-7 has achieved this important criteria earlier than expected, "Hurvitz said in a press release. "We hope that each clinical trial will yield conclusive results, such as those obtained with ribociclib." The overall improvement in survival in an incurable disease, such as metastatic breast cancer, is a remarkable improvement for patients. "

Based on the 2018 PFS results, the FDA has extended the indication of the CDK inhibitor 4/6 in combination with an aromatase inhibitor (IA) in pre- or perimenopausal women with diabetes mellitus. Advanced or metastatic breast cancer HR + / HER2, as an initial endocrine treatment. therapy. Ribociclib has also been approved in association with fulvestrant in postmenopausal women with advanced or metastatic HR + / HER2- breast cancer, as initial endocrine therapy or as a result of the progression of endocrine therapy.

Patients were assigned to ribociclib or placebo in addition to endocrine therapy, particularly goserelin and nonsteroidal AI or tamoxifen. A total of 672 patients were included in the Intent to Treat (ITT) population. There were 83 deaths in 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 observed in the subgroup of 495 AS patients was consistent with those of the general ITT population (HR 0.70 for death, 95% CI from 0.50 to 0.98). In addition, 68.9% of patients in the ribociclib group and 73.2% of patients in the placebo group received subsequent antineoplastic therapy.

Patients in the study group also observed a longer delay between randomization and disease progression during second-line treatment or until death compared to placebo (HR = 0.69 for progression of the disease or death, 95% CI 0.55 to 0.87).

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%
• Extended QT interval: 1.8%; 1.2%

Hurvitz and colleagues noted that more cases of QT prolongation were observed in patients who received the study drug, or placebo, and tamoxifen compared to those in the study. who received ribociclib and AI.

"I think one of the strengths of these data is that they can improve global access in areas where the SO needs to be demonstrated so that governments and institutions can provide that kind of drug to patients, "said Hurvitz.

Harold Burstein, MD, Ph.D., spokesperson for ASCO, of the Dana-Farber Cancer Institute in Boston, said: "This is an important study because it shows that the class of drugs containing CDK4 / 6 inhibitors – which we use commonly and for a long time – shown to delay the progression of treatment – delay the time required for chemotherapy in breast cancer, and double the effectiveness of l & # 39; endocrine, [and] Now, this also translates into a significant benefit for the survival of women with positive estrogen-receptor breast cancer. "

Burstein agreed that the population of younger patients in MONALEESA 7 was important; other trials using CDK 4/6 inhibitors, such as PALOMA-3, included premenopausal and postmenopausal women 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 said. MedPage today.

2019-02-06T00: 00: 00-0500

Last update 06/02/2019