FDA Approves New Drug For Chemo-Related Nausea and Vomiting

September 3, 2015

The US Food and Drug Administration has approved rolapitant for the prevention of delayed phase nausea and vomiting associated with chemotherapy.

The US Food and Drug Administration (FDA) approved rolapitant (Varubi) yesterday to prevent delayed phase nausea and vomiting associated with chemotherapy. These delayed phase symptoms can occur from within 24 hours to 5 days after administration of chemotherapy for cancer treatment. Rolapitant may be prescribed along with other anti-emetic drugs that can prevent nausea and vomiting, according to the label.

“While important strides in preventing nausea and vomiting associated with chemotherapy have been made, still up to half of patients receiving emetogenic cancer chemotherapy can experience delayed chemotherapy-induced nausea and vomiting,” said Richard J. Gralla, MD, professor of medicine at the Albert Einstein College of Medicine in New York, in a press release.

Rolapitant is a selective and competitive antagonist of neurokinin 1 (NK-1) receptors. The approval was based on three phase III clinical trials that showed a significant reduction in episodes of vomiting or the use of rescue anti-emetic drugs in the 25 to 120 hours after chemotherapy administration. Patients treated with rolapitant reported both fewer episodes of nausea that interfered with their day-to-day life and fewer vomiting or retching episodes during multiple chemotherapy cycles.

“Because NK-1 receptors are key drivers of chemotherapy-induced nausea and vomiting, especially in the delayed phase, NK-1 receptor antagonists such as rolapitant, when combined with a 5-HT3 receptor antagonist, and a corticosteroid, provide enhanced protection from chemotherapy-induced nausea and vomiting, and do so in the delayed timeframe where the most help is needed,” added Gralla.

Rolapitant is administered as a 180 mg oral pill in combination with granisetron, an 5-HT3 receptor antagonist, and dexamethasone about 1 to 2 hours before the administration of chemotherapy.

Besides being unpleasant to experience, nausea and vomiting during a chemotherapy regimen can lead to detrimental effects for cancer patients including dehydration, weight loss, and malnutrition.

The three clinical trials enrolled more than 2,500 patients who received highly and moderately emetogenic chemotherapies. Those patients who received the combination of granisetron, dexamethasone, and rolapitant experienced less delayed phase vomiting compared with those who were treated with granisetron and dexamethasone alone.

Two of the clinical trials tested rolapitant in patients receiving cisplatin-based chemotherapy. In the highly emetogenic chemotherapy 1 (HEC1) trial, 72.7% of patients in the rolapitant arm achieved a complete response-the primary endpoint-compared with 58.4% in the placebo group (P = .0006). In the HEC2 trial, 70.1% of patients in the rolapitant arm achieved a complete response compared with 61.9% in the placebo arm (P = .0426). The most common side effects experienced by patients in the trials were neutropenia, hiccups, and abdominal pain. These results were published in Lancet Oncology.

A third phase III trial of more than 1,300 patients tested the efficacy of rolapitant in patients receiving moderately emetogenic chemotherapies including anthracycline/cyclophosphamide combinations, carboplatin, and irinotecan. In this trial, 71.3% of patients in the experimental arm achieved a complete response compared with 61.6% in the placebo arm (P < .0002). The trial results are published in Lancet Oncology. The most common side effects were decreased appetite, neutropenia, dizziness, dyspepsia, urinary tract infection, stomatitis, and anemia.