The European Medicines Agency (EMA) issued four new positive opinions for drug approval or indication expansion in oncology and hematology on 22 June 2017. This included new treatments for hormone receptor (HR)-positive breast cancer, renal cell carcinoma (RCC), and hepatocellular carcinoma (HCC).
- EMA recommended a new indication for fulvestrant (Faslodex®, AstraZeneca) in advanced estrogen receptor (ER)-positive breast cancer to include postmenopausal women not previously treated with endocrine therapy. Fulvestrant was previously approved for treatment of advanced ER-positive breast cancer in women with disease relapse on or after adjuvant antiestrogen therapy or disease progression on antiestrogen therapy. This change in indication was based on the phase III FALCON trial, where fulvestrant improved progression-free survival (PFS) by 2.8 months compared to anastrozole in women who had not received prior endocrine therapy. The adverse event (AE) profile of fulvestrant was consistent with that seen in other indications.
- The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor ribociclib (Kisqali®, Novartis) in combination with an aromatase inhibitor was also recommended for approval as initial treatment for postmenopausal women with advanced HR-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This recommendation was given based on interim results from the phase III MONALEESA-2 trial, where the addition of ribociclib to letrozole resulted in a 44% reduction in the risk of progression or death compared to letrozole alone, with a PFS of 25.3 months compared to 16.0 months (HR 0.568, P<.0001). Ribociclib increased rates of treatment-related AEs, including grade 3/4 neutropenia (60% vs 0.9%) and leukopenia (21% vs 0.6%).
- The EMA recommended an extension of the indication of regorafenib (Stivarga®, Bayer) to include treatment of patients with HCC who have previously been treated with sorafenib. Approval of regorafenib both in Europe and the United States was based on results of the phase III RESORCE trial, recently published in The Lancet.
- The vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) tivozanib hydrochloride monohydrate (Fotivda™, EUSA Pharma) received a positive EMA opinion for the treatment of patients with advanced RCC who are VEGFR and mammalian target of rapamycin (mTOR) inhibitor naïve (untreated or failed prior cytokine therapy). This approval was based on results from the phase III TiVO-1 trial, in which tivozanib was associated with a 2.8-month improvement in PFS over sorafenib (11.9 months vs 9.1 months; HR 0.797, P = .042). In patients who were treatment naïve, tivozanib improved PFS by 3.6 months (HR 0.756, P = .037). Tivozanib did not improve median overall survival compared to sorafenib (28.8 months vs 29.3 months), but was associated with a more favorable AE profile, including decreased rates of VEGFR TKI-associated AEs. Tivozanib is not approved in the United States.