Photo by Rhoda Baer
The US Food and Drug Administration (FDA) has approved rolapitant (Varubi) for use in adult cancer patients receiving initial and repeat courses of emetogenic chemotherapy.
Rolapitant is to be used in combination with other antiemetic agents to prevent delayed chemotherapy-induced nausea and vomiting (CINV).
Tesaro, Inc., the company developing rolapitant, plans to launch the drug in the fourth quarter of this year.
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. Activation of NK-1 receptors plays a central role in CINV, particularly in the delayed phase (the 25- to 120-hour period after chemotherapy administration).
Rolapitant comes in tablet form. The recommended dose is 180 mg, given approximately 1 to 2 hours prior to chemotherapy administration in combination with a 5-HT3 receptor antagonist and dexamethasone. No dosage adjustment is required for dexamethasone when administering rolapitant.
Rolapitant inhibits the CYP2D6 enzyme, so it is contraindicated with the use of thioridazine, a drug metabolized by the CYP2D6 enzyme. Use of these drugs together may increase the amount of thioridazine in the blood and cause an abnormal heart rhythm that can be serious.
Rolapitant clinical trials
Results from three phase 3 trials suggested that rolapitant (at 180 mg) in combination with a 5-HT3 receptor antagonist and dexamethasone was more effective than the 5-HT3 receptor antagonist and dexamethasone on their own (active control).
The 3-drug combination demonstrated a significant reduction in episodes of vomiting or use of rescue medication during the 25- to 120-hour period following administration of highly emetogenic and moderately emetogenic chemotherapy regimens.
In addition, patients who received rolapitant reported experiencing less nausea that interfered with normal daily life and fewer episodes of vomiting or retching over multiple cycles of chemotherapy.
Highly emetogenic chemotherapy
The clinical profile of rolapitant in cisplatin-based, highly emetogenic chemotherapy (HEC) was confirmed in two phase 3 studies: HEC1 and HEC2. Results from these trials were recently published in The Lancet Oncology.
Both trials met their primary endpoint of complete response (CR) and demonstrated statistical superiority of the rolapitant combination compared to active control.
In HEC1, 264 patients received the rolapitant combination, and 262 received active control. The proportion of patients achieving a CR was 72.7% and 58.4%, respectively (P<0.001).
In HEC2, 271 patients received the rolapitant combination, and 273 received active control. The proportion of patients achieving a CR was 70.1% and 61.9%, respectively (P=0.043).
The most common adverse events (≥3%) were neutropenia (9% rolapitant and 8% control), hiccups (5% and 4%), and abdominal pain (3% and 2%).
Moderately emetogenic chemotherapy
Researchers conducted another phase 3 trial to compare the rolapitant combination with active control in 1332 patients receiving moderately emetogenic chemotherapy regimens. Results from this trial were recently published in The Lancet Oncology.
This trial met its primary endpoint of CR and demonstrated statistical superiority of the rolapitant combination compared to active control. The proportion of patients achieving a CR was 71.3% and 61.6%, respectively (P<0.001).
The most common adverse events (≥3%) were decreased appetite (9% rolapitant and 7% control), neutropenia (7% and 6%), dizziness (6% and 4%), dyspepsia (4% and 2%), urinary tract infection (4% and 3%), stomatitis (4% and 2%), and anemia (3% and 2%).
The full prescribing information for rolapitant is available at www.varubirx.com.
