General Information

Varubi (rolapitant) is a substance P/neurokinin 1 (NK1) receptor antagonist.

Varubi is specifically indicated 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.

Mechanism of Action

Varubi (rolapitant) is a substance P/neurokinin 1 (NK1) receptor antagonist. Rolapitant does not have significant affinity for the NK2 or NK3 receptors or for a battery of other receptors, transporters, enzymes and ion channels. Rolapitant is also active in animal models of chemotherapy-induced emesis.

Side Effects

Adverse effects associated with the use of Varubi may include, but are not limited to, the following:

• Cisplatin Based Highly Emetogenic Chemotherapy:
  • neutropenia
  • hiccups
• Moderately Emetogenic Chemotherapy and Combinations of Anthracycline and Cyclophosphamide:
  • decreased appetite
  • neutropenia
  • dizziness

Dosing/Administration

Varubi is supplied as a tablet for oral administration. The recommended dose is 180 mg rolapitant administered approximately one to two hours prior to the start of chemotherapy. Administer in combination with dexamethasone and a 5-HT3 receptor antagonist. No dosage adjustment for dexamethasone is required. 

Clinical Trial Results

The FDA approval of Varubi was based on three clinical trials.

Cisplatin Based Highly Emetogenic Chemotherapy (HEC)

In two multicenter, randomized, double-blind, parallel group, controlled clinical studies (study 1 and study 2), the Varubi regimen (Varubi, granisetron and dexamethasone) was compared with control therapy (placebo, granisetron and dexamethasone) in patients receiving a chemotherapy regimen that included cisplatin >60 mg/m2. 

Study 1: A total of 532 patients were randomized to either the Varubi regimen (N =266) or control therapy (N =266). A total of 526 patients were included in the evaluation of efficacy. During this study, 82 percent of the patients received a concomitant chemotherapeutic agent in addition to protocol-mandated cisplatin. The most common concomitant chemotherapeutic agents administered during cycle 1 were: gemcitabine (17 percent), paclitaxel (12 percent), fluorouracil (11 percent), etoposide (10 percent), vinorelbine (9 percent), docetaxel (9 percent), pemetrexed (7 percent), doxorubicin (6 percent) and cyclophosphamide (5 percent). The mean cisplatin dose was 77 mg/m2. Study 2: A total of 555 patients were randomized to either the Varubi regimen (N =278) or control therapy (N =277). A total of 544 patients were included in the evaluation of efficacy. During this study, 85 percent of the patients received a concomitant chemotherapeutic agent in addition to protocol-mandated cisplatin. The most common concomitant chemotherapeutic agents administered during cycle 1 were: vinrorelbine (16 percent), gemcitabine (15 percent), fluorouracil (12 percent), etoposide (11 percent), pemetrexed (9 percent), docetaxel (7 percent), paclitaxel (7 percent), epirubicin (5 percent) and capecitabine (4 percent). The mean cisplatin dose was 76 mg/m2. 

 Moderately Emetogenic Chemotherapy and Combinations of Anthracycline and Cyclophosphamide Chemotherapy

Study 3: This multicenter, randomized, double-blind, parallel group, controlled clinical study in moderately emetogenic chemotherapy (MEC), the Varubi regimen (Varubi, granisetron and dexamethasone) was compared with control therapy (placebo, granisetron and dexamethasone) in patients receiving a moderately emetogenic chemotherapy regimen that included at least 50 percent of patients receiving a combination of anthracycline and cyclophosphamide. The percentage of patients who received carboplatin in cycle 1 was 30 percent. A total of 1369 patients were randomized to either the Varubi regimen (N = 684) or control therapy (N = 685). A total of 1332 patients were included in the evaluation of efficacy. 

Results:

The primary endpoint in both studies was complete response (defined as no emetic episodes and no rescue medication) in the delayed phase (25 to 120 hours) of chemotherapy induced nausea and vomiting. 

HEC Study 1: 72.7 percent versus 58.4 percent (p<0.001). 

HEC Study 2: 70.1 percent versus 61.9 percent (p-0.043).

MEC Study 3: 71.3 percent versus 61.6 percent (p<0.001).