Kisqali Plus Endocrine Therapy Improves Survival in Breast Cancer Subgroup

The addition of Kisqali (ribociclib) to standard-of-care endocrine therapy significantly improved overall survival for premenopausal women with advanced hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer compared with endocrine therapy alone.

After 42 months of follow-up, the overall survival rate of 70.2% at 42 months compared with 46.0% for placebo and endocrine therapy.

"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," lead study author Dr. Sara A. Hurvitz, director of the Breast Cancer Clinical Research Program at UCLA Jonsson Comprehensive Cancer Center, said in a press release. "The use of ribociclib as a front-line therapy significantly prolonged overall survival, which is good news for women with this terrible disease."

In the phase 3 MONALEESA-7 trial — which is the first to focus exclusively on women under age 59 who were premenopausal and had advanced breast cancer for which they had not received prior endocrine therapy – the researchers randomly assigned 672 women to receive Kisqali or placebo. In addition, all women also received Zoladex (goserelin), an injectable endocrine therapy that suppresses estrogen, and one of three other therapies:

• the nonsteroidal aromatase inhibitors Femara (letrozole),
• anastrozole (Arimidex), which lower estrogen production, or
• tamoxifen, which blocks the effects of estrogen in breast tissue.

After a median follow-up of 34.6 months, 173 (26%) women were still receiving the therapies, with 116 (35%) still receiving Kisqali and 57 (17%) still receiving the placebo.

The improvement in overall survival rate represented a 29% reduction in the risk of death with the addition of the CDK4/6 inhibitor to endocrine therapy. The 42-month progression-free survival rate was 54.6% with Kisqali compared with 37.8% with placebo, representing a 31% reduction in the risk of progression or death with the combination.

At the 42-month analysis, median overall survival could not be estimated in the Kisqali arm compared with 40.9 months in the placebo group. The median progression-free survival was 23.8 months with Kisqali compared with 13.0 months with placebo.

When analyzing subgroups by type of endocrine therapy, the greatest benefit was observed for patients receiving an NSAID. In this group, 248 patients received Kisqali and 247 were administered placebo. There was a statistically significant 30% reduction in the risk of death observed with the addition of Kisqali. The estimated overall survival rate at 42 months was 69.7% with Kisqali compared with 43.0% for placebo.

In the tamoxifen subgroup, there was not a non-statistically significant 21% reduction in the risk of death with Kisqali. Patient numbers were small in this cohort, with 87 patients in the Kisqali arm and 90 in the placebo group. The 42-month overall survival rate was 71.2% with Kisqali compared with 54.5% with placebo.

"Advanced breast cancer in pre-menopausal women can be very aggressive. It is important and encouraging to see a targeted therapy that significantly increases survival for younger women with this disease," ASCO Expert Dr. Harold J. Burstein, said in a press release.