The European Commission ( EC ) has approved Varuby ( oral Rolapitant tablets ) for the prevention of delayed nausea and vomiting associated with highly and moderately emetogenic cancer chemotherapy in adults.
Chemotherapy-induced nausea and vomiting ( CINV ) is a frequent and debilitating, yet often preventable, side effect of chemotherapy.
Varuby is a selective and competitive antagonist of human substance P / neurokinin 1 ( NK-1 ) receptors that is rapidly absorbed and slowly eliminated, with a plasma half-life of seven days.
A single 180 milligram dose ( two tablets ) of Varuby is to be administered within two hours prior to initiation of each chemotherapy cycle, but at no less than 2‑week intervals, as part of combination therapy.
Results from three global phase 3 trials of Rolapitant demonstrated a significant reduction in episodes of vomiting or use of rescue medication during the 25 to 120 hour period following administration of emetogenic chemotherapy, including Cisplatin, Carboplatin and anthracycline / Cyclophosphamide-based regimens.
In addition, patients who received Rolapitant reported experiencing less nausea that interfered with normal daily life and fewer episodes of vomiting over multiple cycles of chemotherapy.
Results of each of the three phase 3 studies were published in The Lancet Oncology in 2015.
Oral Rolapitant was approved by the FDA ( U.S. Food and Drug Administration ) on September 1, 2015 and is marketed in the United States under the brand name Varubi.
Chemotherapy-induced nausea and vomiting is a debilitating, yet often preventable, side effect of chemotherapy. Up to 50% of patients undergoing highly or moderately emetogenic chemotherapy experience delayed CINV ( more than 24 to 120 hours post chemotherapy ) even when prescribed a 5-HT3 receptor antagonist and a 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 Rolapitant to an antiemetic regimen, including a 5-HT3 receptor antagonist and corticosteroid, within two hours prior to each chemotherapy cycle as part of combination therapy further improves prevention of delayed CINV.
The efficacy of oral Rolapitant was established in multiple randomized, well-controlled, international, blinded clinical trials 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 moderately or highly emetogenic chemotherapy.
The clinical profile of oral 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 plus 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 complete response was 72.7% vs. 58.4% ( p less than or equal to 0.001 ).
In HEC2, 271 patients received Rolapitant and 273 received control. The proportion of patients achieving a complete response was 70.1% vs. 61.9% ( p=0.043 ).
The most common adverse reactions ( greater than or equal to 3% ) among patients receiving Cisplatin-based chemotherapy were neutropenia ( 9% Rolapitant versus 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 complete response, and demonstrated statistical superiority of Rolapitant 180 mg compared to active control ( 5-HT3 receptor antagonist plus Dexamethasone ) in the delayed phase of CINV.
The proportion of patients achieving a complete response was 71.3% vs 61.6% ( p less than or equal to 0.001 ).
The most common adverse reactions ( greater than or equal to 3% ) among patients receiving these chemotherapies were 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% ). ( Xagena )
Source: Tesaro, 2017