The FDA ( US Food and Drug Administration ) has approved Kisqali ( Ribociclib ) for women with hormone-receptor positive, human epidermal growth factor receptor-2 negative ( HR+/HER2- ) advanced or metastatic breast cancer.
Kisqali is now the only CDK4/6 inhibitor indicated for use with an aromatase inhibitor for the treatment of pre-, peri- or postmenopausal women in the US ( United States ), and also is indicated for use in combination with Fulvestrant as both first- or second-line therapy in postmenopausal women.
FDA reviewed this supplemental New Drug Application ( sNDA ) under its Real-Time Oncology Review and Assessment Aid pilot programs and approved the application in less than one month after submission.
This approval is based on the pivotal MONALEESA-7 and MONALEESA-3 phase III clinical trials that demonstrated prolonged progression-free survival ( PFS ) and improvements as early as eight weeks for Kisqali-based regimens compared to endocrine therapy alone.
In MONALEESA-7, Kisqali plus an aromatase inhibitor and Goserelin nearly doubled the median PFS compared to an aromatase inhibitor and Goserelin alone ( 27.5 months compared to 13.8 months; hazard ratio, HR=0.569; 95% CI: 0.436-0.743 ) in pre- or perimenopausal women.
In MONALEESA-3, Kisqali plus Fulvestrant demonstrated a median PFS of 20.5 months compared to 12.8 months for Fulvestrant alone ( HR=0.593; 95% CI: 0.480-0.732 ) across the overall population of first-line and second-line postmenopausal women.
Approximately 155,000 people in the US are living with metastatic breast cancer. Up to one-third of patients with early-stage breast cancer will subsequently develop advanced disease, for which there is currently no cure.
Advanced breast cancer in premenopausal women is a biologically distinct and more aggressive disease, and it is the leading cause of cancer death in women 20-59 years old.
MONALEESA-7 is the only phase III global registration trial investigating the efficacy and safety of a CDK4/6 inhibitor, Ribociclib, in combination with an aromatase inhibitor plus Goserelin versus an aromatase inhibitor plus Goserelin, in pre- or perimenopausal women with HR+/HER2- advanced breast cancer who had not previously received endocrine therapy for advanced disease.
Results from the pre-specified NSAI-only subgroup of 495 pre- or perimenopausal women with HR+/HER2- advanced breast cancer who received no prior endocrine therapy for advanced disease showed an estimated median progression-free survival ( PFS, RECIST 1.1 ) of 27.5 months for patients on the Ribociclib arm compared with 13.8 months for those on the placebo arm ( HR 0.569; 95% CI: 0.436, 0.743 ).
Kisqali is not indicated for concomitant use with Tamoxifen.
MONALEESA-3 is a phase III global registration trial evaluating Kisqali in combination with Fulvestrant compared to Fulvestrant alone in postmenopausal women with HR+/HER2- advanced breast cancer who have received no or a maximum of one prior endocrine therapy.
Nearly 70% of patients in MONALEESA-3 receiving Ribociclib plus Fulvestrant as initial therapy were estimated to remain progression-free at the median follow-up of 16.5 months ( median PFS not reached vs.18.3 months; HR=0.577; 95% CI: 0.415-0.802 ).
MONALEESA-2 is a phase III global registration trial evaluating Ribociclib in combination with Letrozole compared to Letrozole alone in postmenopausal women with HR+/HER2- advanced breast cancer who received no prior therapy for advanced breast cancer that led to the initial FDA approval.
MONALEESA-2 is ongoing to evaluate overall survival.
Across the pivotal trials ( M2, M3, and M7 ), the most common adverse reactions ( incidence greater than or equal to 20% ) were neutropenia, nausea, infections, fatigue, diarrhea, leukopenia, vomiting, alopecia, headache, constipation, rash and cough.
Ribociclib is a selective cyclin-dependent kinase inhibitor, a class of drugs that help slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 ( CDK4/6 ).
These proteins, when over-activated, can enable cancer cells to grow and divide too quickly. ( Xagena )
Source: Novartis, 2018