Varubi™(rolapitant) Approved for Chemotherapy-Induced Nausea and Vomiting

Sara Griffin, Mercer University College of Pharmacy

Varubi™ (rolapitant) was approved by the United States Food and Drug Administration (FDA) on September 2, 2015 for the prevention of delayed phase chemotherapy-induced nausea and vomiting. Activation of neurokinin-1 (NK-1) receptors caused by certain chemotherapies leads to nausea and vomiting, especially in the delayed phase. Varubi™ is a substance P/NK-1 receptor antagonist that works to keep NK-1 receptors from becoming activated, reducing chemotherapy-induced nausea and vomiting.1

Delayed chemotherapy-induced nausea and vomiting occurs once more than 24 hours have passed since chemotherapy was administered. Those who experience acute emesis with chemotherapy are significantly more likely to experience delayed emesis. A rating system for chemotherapeutic agents and their respective risk of acute and delayed emesis was developed by the American Society of Clinical Oncology (ASCO). Current recommendations for the prevention of delayed emesis are aprepitant and dexamethasone starting with chemotherapy.2

Title: Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of moderately emetogenic chemotherapy or anthracycline and cyclophosphamide regimens in patients with cancer: a randomised, active-controlled, double-blind, phase 3 trial3
Design Global, randomized, double-blind, active-controlled, phase 3 study; N = 1369
Objective To assess the neurokinin-1 receptor antagonist rolapitant, in combination with a serotonin (5-HT3) receptor antagonist and dexamethasone, for the prevention of chemotherapy-induced nausea and vomiting in patients with cancer after administration of moderately emetogenic chemotherapy or regimens containing an anthracycline and cyclophosphamide
Study Groups Placebo (n = 685) or rolapitant 180 mg (n = 684)
Methods Patients 18 years or older with cancer who had not received moderately or highly emetogenic chemotherapy before, with a Karnofsky performance score of 60 or higher, and a predicted life expectancy of 4 months or longer were included in this study. Patients were randomly assigned to receive either oral rolapitant 180 mg or a placebo that was identical in appearance 1-2 hours before administration of moderately emetogenic chemotherapy. All patients received oral granisetron 2 mg and oral dexamethasone 20 mg on day one (except for patients receiving taxanes as part of moderately emetogenic chemotherapy, who received dexamethasone according to the package insert) and granisetron (2 mg orally) on days 2–3. Every cycle was a minimum of 14 days. In up to five subsequent cycles, patients received the same study drug they were assigned in cycle 1, unless they chose to leave the study or were removed at the treating clinician’s discretion. Efficacy analysis was done in the modified intention-to-treat population (comprising all patients who received at least one dose of study drug at a study site compliant with Good Clinical Practice [GCP]).
Duration February 2012 to February 2014
Primary Outcome Measure Proportion of patients achieving a complete response (defined as no emesis or use of rescue medication) in the delayed phase (> 24–120 hours after initiation of chemotherapy) in cycle 1
Baseline Characteristics Rolapitant

(n = 666)

Placebo

(n = 666)

Age, years 58 (22 to 86) 56 (22 to 88)
Female 531 (79.7%) 536 (80.5%)
Geographic region

North America

Europe

Asia or South Africa

Central or South America

216 (32%)

312 (47%)

107 (16%)

31 (5%)

229 (34%)

299 (45%)

106 (16%)

32 (5%)

Results Complete response (%)
Rolapitant

(n = 666)

Placebo

(n = 666)

Odds ratio (95% CI) p-value
Delayed phase

(> 24-120 hours)

475 (71%) 410 (62%) 1.6 (1.2-2.0) 0.0002
Adverse Events Common Adverse Events (treatment-related treatment-emergent): Constipation, fatigue, dizziness, and headache
Serious Adverse Events: None reported
Percentage that Discontinued due to Adverse Events:

Placebo: 1%

Rolapitant: 0.9%

Study Author Conclusions Rolapitant in combination with a 5-HT3 receptor antagonist and dexamethasone is well tolerated and shows superiority over active control for the prevention of chemotherapy-induced nausea and vomiting during the 5-day (0–120 hours) at-risk period after administration of moderately emetogenic chemotherapy or regimens containing an anthracycline and cyclophosphamide.

All chemotherapy agents received by patients at the time of the study were considered to be moderately emetogenic; however, treatment guidelines for chemotherapy-induced nausea and vomiting regard combined regimens comprising of an anthracycline plus cyclophosphamide as highly emetogenic. Roughly half the patients in the trial received highly emetogenic regimens and the remainder received moderately emetogenic chemotherapy based on the new definitions. Therefore, the results of this study may be applicable to moderately and highly emetogenic chemotherapy categories.3

References

  1. FDA approves new drug treatment for nausea and vomiting from chemotherapy. United States Food and Drug Administration. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm460838.htm. Published September 2, 2015. Accessed September 25, 2015.
  2. Nausea and vomiting-for health professionals (PDQ®). National Cancer Institute. http://www.cancer.gov/about-cancer/treatment/side-effects/nausea/nausea-hp-pdq#link/_50_toc. Updated July 17, 2015. Accessed September 25, 2015.
  3. Schwartzberg LS, Modiano MR, Rapoport BL, et al. Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of moderately emetogenic chemotherapy or anthracycline and cyclophosphamide regimens in patients with cancer: a randomised, active-controlled, double-blind, phase 3 trial. Lancet Oncol. 2015;
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