The Committee for Medicinal Products for Human Use ( CHMP ) of the European Medicines Agency ( EMA ) has adopted a positive opinion recommending an expanded indication for Kisqali ( Ribociclib ), the CDK4/6 inhibitor with the largest body of first-line clinical trial evidence demonstrating consistent, superior and sustained efficacy compared to endocrine therapy alone.
CHMP recommended Kisqali for the treatment of women with hormone receptor positive, human epidermal growth factor receptor-2 negative ( HR+/HER2- ) locally advanced or metastatic breast cancer in combination with Fulvestrant ( Faslodex ) as initial endocrine-based therapy and in women who have received prior endocrine therapy.
CHMP has also recommended approval of Kisqali in combination with endocrine therapy and a luteinising hormone-release hormone agonist ( LHRH ) for pre- and perimenopausal women.
This positive CHMP opinion is based on data from the Phase III MONALEESA-7 and MONALEESA-3 trials.
These trials demonstrated prolonged progression-free survival ( PFS ) for Kisqali-based regimens compared to endocrine therapy alone and showed improvements as early as eight weeks after start of treatment with Kisqali combination therapy.
In MONALEESA-7, Kisqali plus an aromatase inhibitor and Goserelin nearly doubled the median PFS compared to an aromatase inhibitor and Goserelin alone in pre- or perimenopausal women ( 27.5 months compared to 13.8 months; HR=0.569; 95% CI: 0.436-0.743 ).
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.
Across the two trials, the most common adverse reactions ( incidence gretaer than or equal to 20% ) were neutropenia, nausea, infections, fatigue, diarrhea, leukopenia, vomiting, alopecia, headache, constipation, rash and cough.
Globally, an estimated 267,000 women will be diagnosed with advanced breast cancer each year and up to one-third of patients with early-stage breast cancer will subsequently develop advanced disease.
One in five women diagnosed with breast cancer in Europe are younger than 50 years old.
Premenopausal breast cancer is a biologically distinct and more aggressive disease than postmenopausal breast cancer, and it is the leading cause of cancer death in women 20-59 years old.
Kisqali 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. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably. ( Xagena )
Source: Novartis, 2018