European Commission Approves Oral Rolapitant for CINV

Florian Scotté, MD, PhD

The European Commission has approved oral rolapitant tablets (Varuby) for the treatment of delayed chemotherapy-induced nausea and vomiting (CINV) in adults.

The approval applies to all 28 EU member states as well as in the European Economic Area (EEA) countries of Iceland, Lichtenstein and Norway. Tesaro, the drug’s manufacturer, plans to begin introducing rolapitant on a country-by-country basis by the end of June.

The FDA approved rolapitant in September 2015. The drug is marketed as Varubi in the United States.

“While important progress in the treatment and prevention of delayed CINV has been made, nausea and vomiting continue to be 2 of the most common and distressing side effects of cancer chemotherapy,” Florian Scotté, MD, PhD, head of the Functional Unit of Supportive Care in the department of Medical Oncology at Hôpital Européen Georges Pompidou, said in a statement. “Adding an NK-1 receptor antagonist such as Varuby, which has a 7-day half-life and greater than 90% receptor occupancy in the cortical regions of the brain 5 days after dosing, can provide enhanced protection from delayed CINV, which can last for several days.”

Rolapitant is a selective and competitive antagonist of human substance P/neurokinin 1 (NK-1) receptors. The EMA’s Committee for Medicinal Products for Human Use recommended approval of the drug in February based on results from 3 phase III clinical trials. Two studies, HEC1 and HEC2, evaluated rolapitant in patients receiving cisplatin-based highly emetogenic chemotherapy (HEC), the other looked at rolapitant in patients receiving moderately emetogenic chemotherapy (MEC).

Patients in both HEC trials received 180 mg oral rolapitant or placebo before HEC administration, as well as 10 μg/kg IV of the 5HT3-antagonist granisetron and 20 mg of oral dexamethasone on day 1, and 8 mg of oral dexamethasone twice daily on days 2 to 4 of the treatment cycle. A cycle lasted a minimum of 14 days, and patients could undergo up to 5 treatment cycles.

Complete response (CR) in the delayed phase of CINV, defined as 25 to 120 hours after the start of treatment, was 72.7% in the rolapitant arm compared with 58.4% for placebo (P <.001) in HEC1. In HEC2, CR was 70.1% for rolapitant compared with 61.9% for placebo (P = .043).

The most frequently reported adverse events (AEs) were neutropenia (9% with rolapitant vs 8% with control), hiccups (5% vs 4%), and abdominal pain (3% vs 2%).

Researchers evaluated the same dose of rolapitant in the MEC trial. As in the HEC trials, patients were assigned rolapitant or placebo prior to MEC, and both groups received granisetron and dexamethasone. MEC regimens included anthracycline/cyclophosphamide combinations, carboplatin, irinotecan, pemetrexed, oxaliplatin, and doxorubicin. The primary endpoint remained CR in the delayed phase of CINV.

CR was 71.3% in the rolapitant arm compared with 61.6% for patients receiving granisetron plus dexamethasone (P <.001). AEs occurring in ≥3% of patients were similar between the 2 groups, with the most common being decreased appetite (9% for rolapitant vs 7% for placebo), neutropenia (7% for rolapitant vs 6% for placebo), and dizziness (6% for rolapitant vs 4% for placebo).

Patients assigned to rolapitant also reported experiencing less nausea that interfered with normal daily life and fewer episodes of vomiting over multiple cycles of chemotherapy.

“With more than half of patients treated with emetogenic chemotherapy experiencing delayed nausea and vomiting, the approval of Varuby will give physicians in Europe a new option to help prevent this serious side effect,” Orlando Oliveira, senior vice president and general manager of Tesaro International, said in a statement. “This approval represents an important milestone in TESARO’s international expansion. With TESARO operating in 17 European countries, we look forward to bringing this important medicine to patients as quickly as possible.”