Rolapitant-Based Triple Regimen Combats Chemotherapy Emesis

Findings from three phase III trials support the use of a rolapitant-based regimen for the prevention of nausea and vomiting after moderately or highly emetogenic chemotherapy

  • Date: 12 Aug 2015
  • Author: Lynda Williams, Senior medwireNews Reporter
  • Topic: Supportive Care

medwireNews: Research suggests that the novel, long-lasting neurokinin (NK)-1 Receptor antagonist rolapitant, given in combination with the serotonin (5-HT3) receptor antagonist granisetron and dexamethasone, is effective for the treatment of delayed nausea and vomiting in cancer patients undergoing moderately or highly emetic chemotherapy.

Combined results for two phase III trials comparing the rolapitant regimen with placebo plus the 5-HT3 receptor antagonist and steroid in patients undergoing cisplatin-based chemotherapy were reported by Bernardo Rapoport, from The Medical Oncology Centre of Rosebank in Johannesburg, South Africa, and colleagues.

Pooled together, 535 patients received at least one dose of the rolapitant regimen while the same number received the active control; patients were assessed for a complete response in the delayed phase of cycle 1 of chemotherapy, defined as no emesis or need for rescue medication between 24 and 120 hours after initiation. 

Patients randomly assigned to receive rolapitant treatment were a significant 1.6 times more likely to achieve a complete response than those given the active control, at a rate of 71% versus 60%.

Pooled data also showed a significantly higher complete response rate in the acute phase – defined as the first 24 hours of treatment – for patients given rolapitant versus active control (odds ratio [OR]=1.6) and the combined acute and delayed phases (OR=1.6). However, only one of the two trials showed significant benefits for rolapitant in the acute phase when assessed separately.

These findings were reported in The Lancet Oncology alongside a third study comparing the rolapitant and placebo regimens in cancer patients being treated with moderately emetogenic chemotherapy, although almost half the patients received regimens containing an anthracycline and cyclophosphamide, which given together are considered to be highly emetogenic.

Lee Schwartzberg, from The West Clinic in Memphis, Tennessee, USA, and co-authors say a complete response in the delayed phase was significantly more common in the 684 patients randomly assigned to receive rolapitant than the 685 patients given active control, at 71% versus 62% and an OR of 1.6.

Patients were also significantly more likely to have no emesis between 0 and 120 hours after chemotherapy if they were treated with rolapitant than active controls (79 vs 65%, OR=2.0) and significantly more likely to have had complete protection, including no significant nausea or use of rescue medication (62 vs 53%, OR=1.4). 

The studies report the rolapitant regimen as being “well tolerated” and with a similar profile of treatment-emergent events to that found in patients given the active control.

Noting that rolapitant’s lack of interaction with the drug metabolism enzyme CYP3A4 reduces the likelihood of drug–drug interactions, Bernardo Rapoport et al comment: “This simpler regimen could result in better overall cancer treatment adherence in patients receiving highly emetogenic chemotherapy.”

Ian Olver, from the University of South Australia in Adelaide, observes in an accompanying comment that, as evidence-based medicine guidelines recommend triple antiemetic therapy for patients undergoing highly emetic treatment, the two-drug control arm used in the three trials is “ethically problematic”. 

Nevertheless, he recommends further research to determine whether longer acting NK-1 receptor antagonists like rolapitant are more effective than first-generation versions of the agents, especially when given in combination with the second-generation 5-HT3 receptor antagonist palonosetron.

“It would be advantageous if such combinations could enable a reduction in the high doses of steroids that are part of current antiemetic regimens”, he notes.

References 

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 randomised, active-controlled, double-blind, phase 3 trials. Lancet Oncol 2015; Advance online publication 10 August. DOI: http://dx.doi.org/10.1016/S1470-2045(15)00035-2

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. Lancet Oncol 2015; Advance online publication 10 August. DOI: http://dx.doi.org/10.1016/S1470-2045(15)00034-0

Olver I. Role of rolapitant in chemotherapy-induced emesis. Lancet Oncol 2015; Advance online publication 10 August. DOI: http://dx.doi.org/10.1016/S1470-2045(15)00096-0

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