Kisqali (ribociclib) now can be used in combination with an aromatase inhibitor as first-line therapy for all women with HR-positive, HER2-negative advanced or metastatic breast cancer in the United States, regardless of their menopausal status, according to Novartis.
This combination already was approved for postmenopausal women with HR-positive, HER2-negative breast cancer, and the label expansion makes Kisqali the first CDK4/6 inhibitor indicated for women in all menopausal stages, including those who have not reached menopause (premenopausal) or who are in menopause transition (perimenopausal).
In addition, the U.S. Food and Drug Administration (FDA) also approved Kisqali in combination with Faslodex (fulvestrant) as first- or second-line therapy for postmenopausal women with HR-positive, HER2-negative advanced breast cancer.
“Compelling data for Kisqali have led to the broadest first-line indications of any CDK4/6 inhibitor,” Liz Barrett, CEO, Novartis Oncology, said in a press release. “With this new approval Kisqali has the potential to help even more people in the U.S. live a longer life without progression of disease from this incurable form of breast cancer.”
The approval was supported by data from the MONALEESA-7 (NCT02278120) and MONALEESA-3 (NCT02422615) Phase 3 clinical trials. It was granted less than one month after Novartis submitted its application, under the FDA’s Real-Time Oncology Review and Assessment Aid pilot programs.
The FDA previously granted priority review and breakthrough therapy designation to Kisqali for the treatment of pre- and perimenopausal women.
Novartis is discussing MONALEESA-3 and MONALEESA-7 data with other global health authorities to support future submissions and label expansions in other countries.
“Premenopausal women diagnosed with advanced breast cancer often face unique social challenges and a poorer prognosis. For the first time in nearly 20 years, we have results from a dedicated clinical trial among these women,” said Jennifer Merschdorf, CEO of the Young Survival Coalition. “With this approval, some younger women now have a new therapy indicated specifically for them that may help extend their lives without progression of disease.”
MONALEESA-7 enrolled 672 women ages 25 to 58 with advanced or metastatic breast cancer whose tumors were positive for the hormone receptor (HR), but negative for the human epidermal growth factor receptor-2 (HER2). Patients had not received any prior endocrine therapy for their advanced disease.
Participants were randomized to receive either an aromatase inhibitor — Femara (letrozole) or Arimidex (anastrozole) – plus goserelin and Kiskali or an aromatase inhibitor and goserelin alone. (Aromatase inhibitors are medicines that work by blocking the enzyme aromatase, the enzyme that converts androgens into estrogen).
The addition of Kiskali significantly extended the time a patient lived without disease worsening, from 13.8 months to 27.5 months. This represented a 43.2 percent reduction in the risk of disease progression or death.
A combination of Kisqali and tamoxifen also was studied in the trial, but the benefit of this combination was lower – 11.1 months delay in disease progression or death compared to tamoxifen alone.
MONALEESA-3, on the other hand, included 668 patients who had received up to one prior endocrine therapy. Patients had HR-positive, HER2-negative advanced breast cancer and were randomly given Kisqali plus Faslodex, or Faslodex alone.
After a median follow-up of 16.5 months, 70 percent of patients receiving the Kisqali combination were alive and without signs of disease progression. At this point, Kisqali is estimated to reduce the risk of death or disease progression by 42 percent.
“These MONALEESA clinical trial program data add to the body of evidence that CDK 4/6 inhibition, in the case of these studies with ribociclib [Kisqali], gives women diagnosed with HR+/HER2- advanced breast cancer an important first-line treatment option,” said Dennis J. Slamon, MD, director of Clinical/Translational Research, University of California, Los Angeles Jonsson Comprehensive Cancer Center. “Based on Phase 3 trial results that consistently showed clinical benefit, physicians should be encouraged to re-evaluate treatment for advanced breast cancer in the first-line setting.”
For patients in the U.S., Novartis if offering a Kisqali patient support program to provide support and guidance through the various aspects of getting started on treatment. Patients and healthcare professionals can seek more information by calling (800)-282-7630.
The company is conducting additional clinical studies to further assess the potential of Kisqali.
The Phase 3b CompLEEment-1 trial (NCT02941926) is evaluating Kisqali plus Femara in men, and pre- or postmenopausal women with HR-positive, HER2-negative previously untreated advanced breast cancer. The trial is being conducted in approximately 525 clinical centers across the world and is recruiting participants.
For additional information on CompLEEment-1 trial, visit its registry page.
Novartis also has established a collaboration with the Translational Research In Oncology (TRIO) group to develop Kisqali as treatment for early breast cancer. As part of this partnership a new Phase 3 trial — called NATALEE — will be launched, and is expected to include more than 4,000 patients worldwide.