dm+d

Unassigned

Lactation Safety Information

Alternative anti-emetic if appropriate
Neurokinin-receptor antagonist
Use for nausea and vomiting associated with chemotherapy will limit its use in breastfeeding
No published evidence of safety
Low levels anticipated in breast milk due to very high protein binding but very long half-life increases risk of accumulation in breastfed infants
4 March 2019

New Medicines

Varuby (EU), Varubi (US)Chemotherapy-induced nausea & vomiting in adults

Information

Varuby (EU), Varubi (US)
New molecular entity
Tesaro
Tesaro

Development and Regulatory status

Launched
Launched
Launched
May 2017
01. PII studies completed; rolapitant demonstrated promising 5-day activity in CINV prevention following a single dose [1].
02. Mar 12: Three PIII studies started (NCT01500226, NCT01499849, NCT01500213) [2]
03. May 14: Company is preparing to file in US in mid-2014 [5].
04. Sept 14: New Drug Application submitted to US FDA for rolapitant for the treatment of chemotherapy-induced nausea and vomiting. [8]
05. Sep 15: Approved in US [11].
06. Sep 15: US launch planned for Q4 15 [11].
07. Nov 15. Launched in US [12].
08. Mar 16: Intravenous formulation filed in US [13].
09. Mar 16: Filed in EU [14].
10. Feb 17: EU positive opinion for Varuby for prevention of delayed nausea and vomiting associated with highly and moderately emetogenic cancer chemotherapy in adults. Varuby is given as part of combination therapy [15].
11. Approved in EU [16].

Jan 18: Safety information for Varubi updated following reports of anaphylaxis/ hypersensitivity reactions post launch. [18]


12. Launched in UK. Pack of two 90mg tablets = £47.42 [17]

Category

Selective neurokinin-1 (NK1) receptor antagonist. 180 mg (two tablets) should be administered within 2 hours prior to initiation of each chemotherapy cycle but at no less than 2-week intervals.
~36% of all patients on chemotherapy report emesis, and 60% report nausea (Support Care Cancer 2012;20:107) There were 223,260 cytotoxic drug items prescribed in England and Wales in 2011 (http://www.ic.nhs.uk/ and https://gov.wales/ ).
Chemotherapy-induced nausea & vomiting in adults
Oral

Trial or other data

01. Apr 12: The PIII programme consists of two randomized, double-blind and placebo controlled studies (n=530 each) of a single 200mg oral dose of rolapitant in patients receiving highly emetogenic chemotherapy (HEC), and one study (n=1,350) of a single 200mg dose of rolapitant in patients receiving moderately emetogenic chemotherapy (MEC). All patients will receive standard care consisting of a 5-HT3 receptor antagonist plus dexamethasone. Control of nausea and vomiting during the acute (0-24 hours), delayed (24-20 hours) and overall (0-120 hours) time periods post administration of chemotherapy will be assessed. The primary outcome of each trial will be based on complete response (no emetic episodes and no use of rescue medication) in the delayed phase. Results are anticipated in H2 2013 [3].
02. Dec 13: Top-line results for 2 phase 3 trials. The first Phase 3 study of rolapitant was an international, multicenter, randomised, double-blind, active-controlled study that enrolled 1,369 cancer patients receiving moderately emetogenic chemotherapy (MEC), approximately half of whom were receiving anthracycline-based treatment for breast cancer. Patients were randomised to receive either control, which consisted of a 5-HT3 receptor antagonist plus dexamethasone, or 200mg of oral rolapitant plus control. The rolapitant arm successfully achieved statistical significance over the control arm for the primary endpoint of complete response (CR), defined as no vomiting and no use of rescue medication, in the delayed phase (the 24 to 120 hour period following initiation of chemotherapy). A greater proportion of patients treated with rolapitant in this trial achieved a CR in the acute and overall phases and experienced no significant nausea compared to the control arm, although statistical significance was not met for these secondary endpoints. [4]
03. Dec 13: The second Phase 3 study of rolapitant was an international, multicenter, randomised, double-blind, active-controlled study that enrolled 555 patients receiving highly emetogenic chemotherapy (HEC), defined as regimens which contain cisplatin at a dose equal to or greater than 60 mg/m2. Patients were randomised to receive either control, which consisted of 5-HT3 receptor antagonist plus dexamethasone, or 200mg of oral rolapitant plus control. Similar to the MEC study, the rolapitant arm in the HEC study successfully achieved statistical significance over the control arm for the primary endpoint of CR in the delayed phase of CINV. A greater proportion of patients treated with rolapitant in this trial achieved a CR in the acute and overall phases and experienced no significant nausea compared to the control arm, although statistical significance was not met for these secondary endpoints. [4]
04. May 14: Tesaro announces that rolapitant met all primary and secondary endpoints in a third PIII trial [6].
05. Jun 14: Positive results from three Phase III studies of rolapitant, an investigational neurokinin-1 (NK-1) receptor antagonist in development for the prevention of chemotherapy-induced nausea and vomiting, have been presented at the 2014 ASCO annual meeting [7].
06. Aug 15: Results of 2 PIII studies looking at the safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of cisplatin-based highly emetogenic chemotherapy have been published in the lancet [9].
07. Aug 15: Results of PIII study (NCT01500226), published in the Lancet Oncology, found that in adults receiving moderately emetogenic chemotherapy, addition of rolapitant to a standard antiemetic regimen of granisetron and dexamethasone increased the rate of complete response (no emesis or use of rescue medication in the delayed phase; 71% vs. 62%; OR 1.6, p=0.0002)[10].
08. Jan 18: Tesaro update prescribing Information for Varubi due to serious adverse reactions. Since its launch, there have been multiple reports of anaphylaxis, anaphylactic shock and “other serious hypersensitivity reactions” during or soon after infusion of Varubi. Some pts required hospitalisation.[18]

Evidence based evaluations