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FDA Approves Rolapitant (Varubi) for Nausea and Vomiting Associated With Cancer Chemotherapy

Commercial launch planned for fourth quarter of 2015

The FDA has given the nod to rolapitant (Varubi, Tesaro, Inc.) in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy (HEC).

Rolapitant is a selective and competitive antagonist of human substance P/neurokinin 1 (NK-1) receptors, with a plasma half-life of approximately 7 days.

Results from three phase III trials of rolapitant demonstrated a significant reduction in episodes of vomiting or in the use of rescue medication during the 25 to 120 hours following the administration of moderately emetogenic chemotherapy (MEC) or HEC regimens. In addition, patients who received rolapitant reported experiencing less nausea that interfered with normal daily life and fewer episodes of vomiting or retching during multiple cycles of chemotherapy.

A 180-mg dose of rolapitant is to be administered approximately 1 to 2 hours before the administration of chemotherapy in combination with a 5-HT3 (serotonin) receptor antagonist and dexamethasone. No dosage adjustment is required for dexamethasone, a cytochrome P450-3A4 substrate, when administering rolapitant.

The efficacy of rolapitant was established in several randomized, controlled, blinded clinical studies that enrolled more than 2,500 patients. Rolapitant, when administered in combination with a 5-HT3 receptor antagonist and dexamethasone, was superior to a 5-HT3 receptor antagonist and dexamethasone in preventing CINV in patients receiving either MEC or HEC.

The clinical profile of rolapitant in cisplatin-based HEC was confirmed in two identical phase III studies: HEC1 and HEC2. Both trials met their primary endpoint of a complete response (CR) and demonstrated the statistical superiority of rolapitant 180 mg compared with active control (5-HT3 receptor antagonist plus dexamethasone) in the delayed phase of CINV (25 to 120 hours after chemotherapy). In the HEC1 trial, 264 patients received rolapitant (180 mg) and 262 received control. The proportions of patients achieving a CR were 73% and 58%, respectively (P < 0.001). In the HEC2 trial, 271 patients received rolapitant and 273 received control. The proportions of patients achieving a CR were 70% and 62%, respectively (P = 0.043). The most common adverse events among patients receiving cisplatin-based chemotherapy included neutropenia (9% rolapitant vs. 8% control), hiccups (5% vs. 4%), and abdominal pain (3% vs. 2%).

A phase III study was also conducted to evaluate rolapitant (180 mg) compared with active control in 1,332 patients receiving MEC or HEC regimens, including anthracycline/cyclophosphamide combinations, carboplatin, irinotecan, pemetrexed, oxaliplatin, and doxorubicin. This study met its primary endpoint of CR and demonstrated the statistical superiority of rolapitant 180 mg compared with active control (5-HT3 receptor antagonist plus dexamethasone) in the delayed phase of CINV. The proportions of patients achieving a CR were 71% and 62%, respectively (P < 0.001). The most common adverse events among patients receiving these chemotherapies included decreased appetite (9% rolapitant vs. 7% control), neutropenia (7% vs. 6%), dizziness (6% vs. 4%), dyspepsia (4% vs. 2%), urinary tract infection (4% vs. 3%), stomatitis (4% vs. 2%), and anemia (3% vs. 2%).

Primary data from the three phase III trials were published online ahead of print in Lancet Oncology.

Source: Tesaro, Inc.; September 2, 2015.

 

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