Novartis Kisqali® received FDA designation for initial endocrine-based treatment with HR+/HER2- advanced breast cancer
Novartis has announced Kisqali® received US Food and Drug Administration (FDA) Breakthrough Therapy designation for the initial endocrine-based treatment of pre- or perimenopausal women with hormone-receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer in combination with tamoxifen or an aromatase inhibitor.
This Breakthrough Therapy designation is 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 significantly prolonged progression-free survival (PFS) compared to endocrine therapy alone vs. 13.0 months. A total of 672 women ranging from 25-58 years in age were enrolled and randomised in the trial. All treatment combinations also included goserelin. Treatment benefit with Kisqali combination therapy was consistent compared to the overall population regardless of treatment with tamoxifen or aromatase inhibitor endocrine partners, and across predefined patient subgroups.
"This Breakthrough Therapy designation reflects the significance and promise of the MONALEESA-7 data presented at SABCS last month," said Samit Hirawat, MD, Head, Novartis Oncology Global Drug Development. "Younger women often have distinct treatment goals and needs, and it is important for oncologists to offer effective and well-studied treatment options for their specific disease. We look forward to working with FDA to make this combination therapy available to premenopausal women living with HR+/HER2- advanced breast cancer in the US as soon as possible."
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 an 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 grade 3/4 adverse events in patients receiving Kisqali combination therapy compared to endocrine therapy alone were neutropenia and leukopenia.
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.
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 the Fast Track program features, as well as more intensive FDA guidance on an efficient drug development program.
This Breakthrough Therapy designation marks the second for Kisqali. The first Breakthrough Therapy designation for Kisqali was granted in August 2016 based on results of the Phase III MONALEESA-2 trial.