FDA Approves Rolapitant for Delayed CINV

The FDA has approved rolapitant injectable emulsion in combination with other antiemetics in adults to prevent delayed chemotherapy-induced nausea and vomiting.

The US Food and Drug Administration (FDA) has approved rolapitant (Varubi®; Tesaro, Inc.) injectable emulsion in combination with other antiemetics in adults to prevent delayed emetogenic chemotherapy-induced nausea and vomiting (CINV; 25 to 120 hours after chemotherapy dosing), the company has announced.

Rolapitant is a “highly selective and competitive antagonist of human substance P/neurokinin 1 (NK-1) receptors,” which are involved in delayed CINV, according to TESARO’s announcement. It has a 7-day half-life in plasma.

A bioequivalence study of healthy volunteers showed that the IV formulation is comparable to the oral formulation.

TESARO-funded phase III clinical trials, published in Lancet Oncology, demonstrated that adding oral rolapitant (180 mg) to an antiemetic regimen of granisetron and dexamethasone significantly improved complete response rates in the delayed phase of CINV among patients undergoing highly emetogenic cisplatin-based chemotherapy, compared with granisetron and dexamethasone without rolapitant (73% vs 58%; odds ratio [OR], 1.9; 95% CI, 1.3–2.7; P = .0006). Phase III trial results also showed similar results for patients undergoing moderately emetogenic chemotherapy with anthracycline and cyclophosphamide regimens (complete response rate, 71%; OR, 1.6; 95% CI, 1.2–2.0; P = .0002).

The clinical trials demonstrated that rolapitant is associated with a significant reduction in the number of episodes of vomiting and the use of rescue medication during the delayed phase following chemotherapy administration. Patients also reported less disruption of daily life by nausea.

Most NK-1 receptor antagonist doses are administered intravenously, noted Mary Lynne Hedley, PhD, president and COO of TESARO. More than half of patients undergoing cancer chemotherapy experience delayed CINV despite standard antiemetic treatments such as a combination of a 5-HT3 receptor antagonist and dexamethasone.

In the bioequivalence study, healthy volunteers were randomly assigned to receive 166.5-mg IV rolapitant (n = 61) or 180-mg oral rolapitant (n = 62). The safety profile was similar and consistent with previous findings with oral rolapitant, other than infusion site reactions among patients receiving the IV formulation.

The most common adverse events were neutropenia, hiccups, loss of appetite, and dizziness. Infusion-related symptoms included warm sensations, abdominal pain, dizziness, and peripheral paresthesia.

Rolapitant should not be used in patients treated with CYP3A4 inducers like rifampin, and digoxin concentrations should be monitored when rolapitant is administered concomitantly, in case dosage adjustments are required.