The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended approval of the breast cancer drug ribociclib (Kisqali, Novartis) and the kidney cancer agent tivozanib (Fotivda, Aveo and EUSA Pharma). It also extended the indications of already-approved drugs for breast and liver cancer.
Ribociclib is used, in combination with an aromatase inhibitor, for treatment of postmenopausal women with hormone receptor–positive, human epidermal growth factor receptor–2–negative (HER+/HER2-) locally advanced or metastatic breast cancer as initial endocrine-based therapy.
Ribociclib is already approved in the United States for this indication.
The positive CHMP opinion is based on results from the pivotal phase 3 MONALEESA-2 trial, which compared ribociclib plus letrozole to letrozole alone in 668 postmenopausal women who had received no prior systemic therapy for their advanced breast cancer.
For ribociclib plus letrozole vs letrozole alone, median progression-free survival was 25.3 months vs 16.0 months (hazard ratio = 0.56, 95% CI, 0.457 – 0.704; P < .0001). The overall response rate was 55% vs 39% (P = .00025). Follow-up to assess overall survival is ongoing because the data remain immature.
Ribociclib will be available as 200-mg film-coated tablets in Europe. The agent is a protein kinase inhibitor that selectively inhibits cyclin-dependent kinase (CDK) 4 and 6. CDK4 and CDK6 are downstream of multiple signaling pathways that lead to cellular proliferation.
The most common side effects are neutropenia, leukopenia, headache, back pain, nausea, fatigue, diarrhea, vomiting, constipation, alopecia, and rash, according to the CHMP.
Renal Cell Carcinoma
The CHMP also presented a positive opinion of tivozanib (Fotivda, Aveo and EUSA Pharma), which is intended for the initial treatment of advanced renal cell carcinoma (RCC).
The full indication is for the “first line treatment of adult patients with advanced RCC and for adult patients who are VEGFR [vascular endothelial growth factor receptor] and mTOR pathway inhibitor-naive following disease progression after one prior treatment with cytokine therapy for advanced RCC.”
An oral, once-daily drug, tivozanib is not approved in the United States. It was rejected by the US Food and Drug Administration in 2013, as reported by Medscape Medical News.
Tivozanib is a protein kinase inhibitor that, by blocking VEGFRs, inhibits angiogenesis, leading to inhibition of tumor growth.
According to the CHMP, tivozanib has been shown to “improve progression-free survival in patients with advanced disease.”
The most common side effects are hypertension, dysphonia, fatigue, and diarrhea.
The CHMP recommended a new indication for regorafenib (Stivarga, Bayer Pharma AG) as a monotherapy for the treatment of adult patients with hepatocellular carcinoma who have been previously treated with sorafenib. It is also indicated for metastatic colorectal cancer and gastrointestinal stromal tumors.
The panel also recommended a change to the terms of the marketing authorization for fulvestrant (Faslodex, AstraZeneca). The new indication is as follows: “Faslodex is indicated for the treatment of estrogen receptor positive, locally advanced or metastatic breast cancer in postmenopausal women not previously treated with endocrine therapy, or with disease relapse on or after adjuvant antiestrogen therapy, or disease progression on antiestrogen therapy.”
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