The U.S. Food and Drug Administration (FDA) has approved rolapitant (trade name varubi) 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.

Chemotherapy-induced nausea and vomiting (CINV) is a debilitating, yet often preventable, side effect of chemotherapy.

Up to 50% of patients undergoing highly or moderately emetogenic chemotherapy experience delayed CINV (25 to 120 hours post chemotherapy)—even when prescribed a 5-HT3 receptor antagonist and corticosteroid.

Blocking both 5-HT3 and NK-1 receptors has been shown to offer better control of nausea and vomiting than inhibiting 5-HT3 receptors alone. Adding a single dose of VARUBI to an antiemetic regimen, including a 5-HT3 receptor antagonist and corticosteroid, further improves prevention of CINV in the delayed Phase following chemotherapy.

The efficacy of rolapitant was established in multiple randomized, well-controlled, blinded clinical trials that enrolled more than 2,500 patients. When administered in combination with a 5-HT3 receptor antagonist and dexamethasone, it was found to be superior to a 5-HT3 receptor antagonist and dexamethasone in preventing CINV in patients receiving either moderately or highly emetogenic chemotherapy.

The clinical profile of rolapitant in cisplatin-based highly emetogenic chemotherapy (HEC) was confirmed in two identical Phase 3 studies: HEC1 and HEC2.

Both trials met their primary endpoint of complete response (CR), and demonstrated statistical superiority of rolapitant 180 mg compared to active control (5-HT3 receptor antagonist dexamethasone) in the delayed Phase (25-120 hours) of CINV. In HEC1, 264 patients received rolapitant 180 mg and 262 received control.

The proportion of patients achieving a CR was 72.7% vs. 58.4% (p= < 0.001). In HEC2, 271 patients received rolapitant and 273 received control. The proportion of patients achieving a CR was 70.1% vs. 61.9% (p=0.043). The most common adverse reactions (≥3%) among patients receiving cisplatin-based chemotherapy were neutropenia (9% VARUBI vs. 8% control), hiccups (5% vs. 4%), and abdominal pain (3% vs. 2%).

A Phase 3 trial was also conducted to evaluate rolapitant 180 mg compared to active control in 1,332 patients receiving moderately emetogenic chemotherapy regimens, including anthracycline/cyclophosphamide combinations, carboplatin, irinotecan, pemetrexed, oxaliplatin, and doxorubicin. This trial met its primary endpoint of CR, and demonstrated statistical superiority of rolapitant 180 mg compared to active control (5-HT3 receptor antagonist dexamethasone) in the delayed Phase of CINV.

The proportion of patients achieving a CR was 71.3% vs 61.6% (p= < 0.001). The most common adverse reactions (≥3%) among patients receiving these chemotherapies were decreased appetite (9% VARUBI 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 3 studies have recently been published online ahead of print in Lancet Oncology, the analysis of the non-AC MEC population was presented at the 2015 annual meeting for the Multinational Association for Supportive Care in Cancer, and commentary has been provided in Nature Reviews Clinical Oncology.

Source: OPKO