On January 03, 2018, Novartis announced that KisqaliR (Ribociclib) has received US Food and Drug Administration (FDA) Breakthrough Therapy designation for initial endocrine-based treatment, in combination with tamoxifen or an aromatase inhibitor51, for pre- or perimenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer.
The Breakthrough Therapy designation was based on positive results of the Phase III MONALEESA-7 trial demonstrating Kisqali in combination with tamoxifen or an aromatase inhibitor as initial endocrine-based therapy showing significantly prolonged progression-free survival (PFS) compared to endocrine therapy alone (median PFS 23.8 (95% CI: 19.2 months-not reached) vs. 13.0 months (95% CI: 11.0-16.4 months); HR=0.553; 95% CI: 0.441-0.694; p<0.0001). A total of 672 women ranging from 25-58 years in age were enrolled and randomized in the trial. All treatment combinations also included goserelin. Treatment benefit with Kisqali combination therapy was consistent across the population regardless of treatment with tamoxifen or aromatase inhibitor endocrine partners, and across predefined patient subgroups52.
MONALEESA-7 was the first Phase III trial entirely dedicated to evaluating a CDK4/6 inhibitor in premenopausal women with HR+/HER2- advanced breast cancer. The trial evaluated Kisqali in combination with oral endocrine therapies (tamoxifen or an aromatase inhibitor) and goserelin compared to oral endocrine therapy and goserelin in this patient population. In subgroup analyses of median PFS by endocrine partner, Kisqali in combination with tamoxifen and goserelin demonstrated 22.1 months median PFS compared to 11.0 months for tamoxifen and goserelin alone; Kisqali in combination with an aromatase inhibitor and goserelin demonstrated 27.5 months median PFS compared to 13.8 months for an aromatase inhibitor and goserelin alone.
No new safety signals were observed in the MONALEESA-7 trial; adverse events were generally consistent with those observed in MONALEESA-2, identified early and mostly managed through dose interruptions or reductions. Combination treatment with Kisqali was well tolerated with a discontinuation rate due to adverse events of 3.6% compared to 3.0% in patients who received endocrine therapy alone. The most common (>=5%) grade 3/4 adverse events in patients receiving Kisqali combination therapy, compared to endocrine therapy alone, were neutropenia (60.6% vs 3.6%) and leukopenia (14.3% vs 1.2%).
Premenopausal breast cancer is a biologically distinct and more aggressive disease than postmenopausal breast cancer, and it is the leading cause of cancer deaths in women 20-59 years of age53.
According to FDA, Breakthrough Therapy designation is intended to expedite the development and review of potential new medicines that treat serious or life-threatening conditions, if the therapy has demonstrated substantial improvement over an available therapy on at least one clinically significant endpoint. The designation includes all of the Fast Track program features, as well as more intensive FDA guidance on an efficient drug development program54.
This Breakthrough Therapy designation marks the second such designation for Kisqali. The first Breakthrough Therapy designation for Kisqali was granted in August 2016 based on results of the Phase III MONALEESA-2 trial.
About Kisqali® (Ribociclib)
Kisqali is a selective cyclin-dependent kinase inhibitor, a class of drugs that helps slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when over-active, can enable cancer cells to grow and divide quickly. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably. Kisqali was approved by the European Commission in August 2017, as initial endocrine-based therapy for postmenopausal women with HR+/HER2- locally advanced or metastatic breast cancer in combination with an aromatase inhibitor based on findings from the pivotal MONALEESA-2 trial.
Footnotes
52. http://www.ascopost.com/News/58328
53. http://www.who.int/mediacentre/factsheets/fs334/en/
54. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM358301.pdf
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