For US healthcare professionals only. Prescribing Information

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

Chart showing how VARUBI increased CR rates in the delayed phase of CINV

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

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

  • IV administration of VARUBI was associated with infusion‐related symptoms in 2.6% of patients (eg, sensation of warmth, abdominal pain, dizziness, and paresthesia).

IV safety profile

  • In healthy subjects receiving the recommended therapeutic dose of VARUBI injectable emulsion, infusion-related adverse reactions were reported in 2.6% (2/78) of subjects during the infusion and included sensation of warmth, abdominal pain, dizziness, and paresthesia
  • Since VARUBI injectable emulsion is the same active substance (rolapitant) as VARUBI tablets, adverse reactions associated with VARUBI tablets might also be expected to occur with VARUBI injectable emulsion

IV postmarketing experience3

  • The following adverse reactions have been identified during post-approval use of VARUBI injectable emulsion: hypersensitivity reactions including anaphylaxis, anaphylactoid reactions, and anaphylactic shock including back pain and chest pain, abdominal pain, erythema, feeling hot, generalized flushing, and dizziness
  • Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure
  • In postmarketing experience, severe systemic reactions have occurred within minutes of the start of infusion with VARUBI injectable emulsion

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

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

  • Patients were randomized to receive VARUBI or placebo on day 1 prior to chemotherapy1,2
  • Both VARUBI and placebo groups received granisetron and dexamethasone, followed by chemotherapy administration1,2
  • Events of emesis and use of rescue medication were recorded for 5 days1,2

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

Study design: HEC studies 1 and 2

a Granisetron dosing on day 1 prior to chemotherapy was 10 mcg/kg IV.2 b Dexamethasone dosing on day 1 prior to chemotherapy was 20 mg PO. Dosing on days 2-4 was 8 mg BID PO.2 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

Study design: MEC study

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); AC, anthracycline and cyclophosphamide; AUC, area under the curve; CR, complete response; HEC, highly emetogenic chemotherapy; 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. Other MEC included cyclophosphamide (<1,500 mg/m2) and irinotecan.2 Since the time of this study, both carboplatin dosed at area under the curve (AUC) ≥ 4 and any combination of anthracycline and cyclophosphamide (AC) have been reclassified as HEC.2,4

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

A 166.5-mg IV infusion of VARUBI demonstrated bioequivalence to a 180-mg oral dose6

Mean (SD) plasma concentrations for VARUBI (0-912 h)6

Graph displaying a 166.5-mg IV infusion of VARUBI demonstrated bioequivalence to a 180-mg oral dose

SD, standard deviation.
Adapted from Wang X et al, 2017.

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.; 2018. 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. 6. Wang X, Zhang Z-Y, Powers D, et al. Bioequivalence of Intravenous and Oral Rolapitant: Results From a Randomized, Open-Label Pivotal Study. J Clin Pharmacol. 2017;57(12):1600-1606. doi:10.1002/jcph.966.