Proven prevention of delayed CINV (25-120 h)

One dose of VARUBI® (rolapitant), as part of an antiemetic regimen, significantly improved complete response (CR) rates in the delayed phase of chemotherapy-induced nausea and vomiting (CINV, 25-120 h)1,2

VARUBI met its primary end point of CR (no vomiting or administration of rescue medication) in the delayed phase of CINV in three independent phase 3 studies of highly and moderately emetogenic chemotherapy (HEC and MEC) in a combined 2,402 patients.3

 

VARUBI increased CR rates (no vomiting or rescue medication) in the delayed phase of CINV1,2

tablet - increased CR Rates mobile - increased CR Rates
 
a HEC study 1, 95% CI for delayed CR: 6.3, 22.4; VARUBI n = 264, control n = 262.3
b HEC study 2, 95% CI for delayed CR: 0.3, 16.1; VARUBI n = 271, control n = 273.3
c MEC study, 95% CI for delayed CR: 4.7, 14.8; VARUBI n = 666, control n = 666.3
d Since the start of the study, AC has been reclassified as HEC.4 Types of MEC included in this study were carboplatin, cyclophosphamide (<1,500 mg/m2), and irinotecan.2
AC, anthracycline and cyclophosphamide; CI, confidence interval; CR, complete response (no vomiting or administration of rescue medication); HEC, highly emetogenic chemotherapy; MEC, moderately emetogenic chemotherapy.
 

Efficacy in multiple-cycle extensions

In HEC studies 1 and 2 and the MEC study, patients had the option of continuing into a multiple-cycle extension for up to 5 additional cycles of chemotherapy, receiving the same treatment as assigned in cycle 1. At days 6 through 8 following initiation of chemotherapy, patients were asked to recall whether they had any episode of vomiting or retching or nausea that interfered with normal daily life.3 Approximately 71%-87% of patients reported no emesis and no nausea interfering with daily life.5

 

Adverse reactions

 

Evaluated in three phase 3 pivotal trials

An antiemetic regimen containing VARUBI was compared with an active-controlled antiemetic regimen in three phase 3, double-blind, global clinical trials1-3

tablet - trials evaluation mobile - trials evaluation
 

5-HT3 RA, 5-hydroxytryptamine-3 (serotonin) receptor antagonist.

 

All phase 3, placebo-controlled, double-blind, randomized, global clinical trials examined the administration of VARUBI or placebo in combination with granisetron and dexamethasone.1-3

Primary end point was complete response (CR, no vomiting or administration of rescue medication) in the delayed phase of CINV (25-120 h)3

 

Study design was similar across three phase 3 trials

mobile - HEC study design HEC study design
a Granisetron dosing on day 1 prior to chemotherapy was 10 mcg/kg IV.1
b Dexamethasone dosing on day 1 prior to chemotherapy was 20 mg PO. Dosing on days 2-4 was 8 mg BID PO.1
5-HT3, 5-hydroxytryptamine-3 (serotonin); BID, twice a day; CR, complete response; HEC, highly emetogenic chemotherapy; IV, intravenous; PO, by mouth; RA, receptor antagonist.

For HEC studies 1 and 2, patients received a chemotherapy regimen that included cisplatin >60 mg/m2.3

 
mobile - MEC study design MEC study design
a Granisetron dosing on day 1 prior to chemotherapy was 2 mg PO. Granisetron dosing on days 2-3 was 2 mg PO daily.2
b Dexamethasone dosing on day 1 prior to chemotherapy was 20 mg PO.2
5-HT3, 5-hydroxytryptamine-3 (serotonin); CR, complete response; MEC, moderately emetogenic chemotherapy; PO, by mouth; RA, receptor antagonist.
 

For the MEC study, more than half of patients in the VARUBI and control groups received AC-based chemotherapy (a combination of an anthracycline and cyclophosphamide), which has since been reclassified as highly emetogenic.2,4 Of non–AC-based MEC, carboplatin was the most commonly administered chemotherapy, comprising 29% of patients in the VARUBI group and 31% of patients in the control group.2 Other MEC included cyclophosphamide (<1,500 mg/m2) and irinotecan.2

 
 

Patient demographics

The VARUBI and control groups were balanced with respect to age, sex, nationality, alcohol consumption, primary tumor site, and type of chemotherapy administered.1,2

 
 

Indication and Important Safety Information for VARUBI® (rolapitant)

Indication

  • VARUBI, in combination with other antiemetic agents, is indicated 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

Contraindication

  • VARUBI is contraindicated in patients receiving thioridazine, a CYP2D6 substrate. A significant increase in plasma concentrations of thioridazine may result in QT prolongation and Torsades de Pointes

Warnings and precautions

Interaction with CYP2D6 substrates with a narrow therapeutic index

  • The inhibitory effect of VARUBI on CYP2D6 lasts for at least 7 days and may last longer after administration of a single dose of VARUBI
  • Avoid use of VARUBI in patients who are receiving pimozide, a CYP2D6 substrate. An increase in plasma concentrations of pimozide may result in QT prolongation
  • Monitor for adverse reactions if concomitant use of VARUBI and other CYP2D6 substrates with a narrow therapeutic index cannot be avoided

Adverse reactions

  • In patients receiving cisplatin-based highly emetogenic chemotherapy in cycle 1, the most common adverse reactions reported at an incidence of ≥5% and a frequency greater than control were neutropenia (9% VARUBI vs 8% control) and hiccups (5% vs 4%)
  • In patients receiving moderately emetogenic chemotherapy and combinations of anthracycline and cyclophosphamide in cycle 1, the most common adverse reactions reported at an incidence of ≥5% and a frequency greater than control were decreased appetite (9% VARUBI vs 7% control), neutropenia (7% vs 6%), and dizziness (6% vs 4%)

Drug interactions

  • VARUBI is an inhibitor of breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp). Increased plasma concentrations of BCRP and P-gp substrates with a narrow therapeutic index may result in potential adverse reactions. Monitor for adverse reactions related to the concomitant drug if use with VARUBI cannot be avoided
  • Avoid use of VARUBI in patients who require chronic administration of strong CYP3A4 inducers (eg, rifampin) as significantly reduced plasma concentrations of VARUBI can decrease the efficacy of VARUBI
 

Please see full Prescribing Information.

 
 

References: 1. Rapoport BL, Chasen MR, Gridelli C, et al. Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of cisplatin-based highly emetogenic chemotherapy in patients with cancer: two randomized, active-controlled, double-blind, phase 3 trials [published online August 11, 2015]. Lancet Oncol. doi:10.1016/S1470-2045(15)00035-2. 2. 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 [published online August 11, 2015]. Lancet Oncol. doi:10.1016/S1470-2045(15)00034-0. 3. VARUBI [package insert]. Waltham, MA: TESARO, Inc.; 2015. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Antiemesis v.2.2015. © National Comprehensive Cancer Network, Inc., 2015. All rights reserved. Accessed October 13, 2015. To view the most recent and complete version of the guideline, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc. 5. Data on file. TESARO, Inc.

 
 
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