According to findings presented at the European Society for Medical Oncology (ESMO) 2014 Congress in Madrid, Spain, rolapitant, a novel neurokinin-1 (NK-1) receptor antagonist, in combination with granisetron and dexamethasone is effective and safe for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic cisplatin-based treatment regimens.
For the phase 3 multicenter, randomized, double-blind study, researchers randomly assigned 532 patients to receive either oral rolapitant in combination with granisetron and dexamethasone or placebo plus granisetron and dexamethasone.
The researchers sought to determine whether the rolapitant treatment regimen was more effective than the placebo regimen at preventing emesis and eliminating the need for rescue medications (complete response) during the delayed phase (>24-120 hours) after chemotherapy. Secondary endpoints included a complete response during the acute phase (0-24 hours) post-chemotherapy and overall phases.1
Patients in the intervention group received rolapitant 200 mg orally, granisetron 10 mcg/kg intravenously, and dexamethasone 20 mg orally on day 1, and dexamethasone 8 mg orally twice a day on days 2 through 4. Patients in the placebo group received the same regimen except substituting rolapitant for placebo.
RELATED: Combo Therapy Better for Chemo-induced Nausea and Vomiting
The researchers found that 72.7% of patients in the rolapitant group achieved a complete response in the delayed phase compared with 58.4% in the placebo group (P < 0.001). In addition, 83.7% of patients in the rolapitant group achieved a complete response in the acute phase versus 73.7% in the placebo group (P = 0.005), and 70.1% of patients in the rolapitant group achieved an overall complete response 56.5% in the placebo group (P = 0.001). The researchers reported that slightly more patients in the rolapitant group experienced no affect on daily quality of life, but the difference was not statistically significant (P = 0.231).1
Findings presented at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois, demonstrated that rolapitant 200 mg orally in combination with granisetron and dexamethasone was also effective at preventing CINV in patients receiving moderately emetogenic chemotherapy.2
As a result of rolapitant’s efficacy for preventing CINV in patients receiving either moderately or highly emetogenic chemotherapy, the novel drug would compete against aprepitant, the first and only NK-1 receptor antagonist approved by the U.S. Food and Drug Administration (FDA).
Both drugs have demonstrated that they fill the unmet need of preventing CINV during the delayed phase post-chemotherapy; however, rolapitant may be preferred over aprepitant for two reasons. First, rolapitant has been studied as a one-time dose on day 1 of chemotherapy, while aprepitant is recommended to be given on days 1 through 3.1-3
Second, rolapitant does not inhibit CYP 2C9 or 3A4 enzymes, whereas aprepitant induces CYP 2C9 and 3A4 and moderately inhibits 3A4.3,4 As a result, aprepitant can interfere with warfarin, hormonal contraceptives, and certain chemotherapy, among other drugs.3 Unlike rolapitant, aprepitant has an intravenous formulation called fosaprepitant, which can be beneficial in those who cannot take oral medications.3
Tesaro Inc. submitted a new drug application to the FDA in early September for approval of oral rolapitant for the prevention of CINV.5
- Chasen M, Poma A, Hedley M, et al. Phase 3 (P04832) trial results for rolapitant, a novel NK-1 receptor antagonist, in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving cisplatin-based therapy. In: Proceedings of the ESMO 2014 Congress; September 26-30, 2014; Madrid, Spain. Abstract LBA47_PR.
- Schnadig ID, Modiano MR, Poma A, et al. Phase 3 trial results for rolapitant, a novel NK-1 receptor antagonist, in the prevention of chemotherapy-induced nausea and vomiting (CINV) in subjects receiving moderately emetogenic chemotherapy (MEC). J Clin Oncol. 2014;32:5s(suppl;abstract 9633).
- Emend [package insert]. Whitehouse Station, NJ: Merck & Co., Inc. https://www.merck.com/product/usa/pi_circulars/e/emend/emend_pi.pdf
- Gan TJ, Gu J, Singla N, et al. Rolapitant for the prevention of postoperative nausea and vomiting: a prospective, double-blinded placebo-controlled randomized trial. Anesth Analg. 2011;112(4):804-812.
- Tesaro announces submission of rolapitant new drug application (NDA) to U.S. Food and Drug Administration. Tesaro Press Releases. Tesaro Inc. http://ir.tesarobio.com/releasedetail.cfm?ReleaseID=869491. Published September 8, 2014. Accessed October 17, 2014.