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

Efficacy of the neurokinin‐1 receptor antagonist rolapitant in preventing nausea and vomiting in patients receiving carboplatin‐based chemotherapy

“…Rolapitant was well tolerated in the carboplatin subgroup, and this was consistent with the safety profile reported in phase 3 studies 12, 13. The incidence of adverse events with rolapitant was comparable to the incidence with the control, and these adverse events were generally considered to be related to chemotherapy or the underlying disease.…”

“…A global, multicenter, randomized, parallel‐group, double‐blind, controlled phase 3 study (NCT01500226) was conducted in 23 countries in North America, Central and South America, Europe, Asia, and Africa 12. The protocol was approved by institutional review boards at each study site, all patients provided written informed consent, and all investigators and site personnel were required to follow ethical principles outlined in the Declaration of Helsinki and consistent with the International Conference on Harmonisation Good Clinical Practice guidelines and applicable local laws and regulations.…”

“…The inclusion of rolapitant in the antiemetic guidelines was based on the results of 3 large, global, randomized, double‐blind, controlled phase 3 studies demonstrating that oral rolapitant combined with a 5‐HT 3 RA and dexamethasone was superior to a 5‐HT 3 RA and dexamethasone alone in providing CINV protection in the delayed phase to patients receiving HEC or MEC 12, 13. The MEC trial was designed before antiemetic guidelines reclassified anthracycline and cyclophosphamide (AC)–based regimens as HEC; therefore, the MEC trial included AC‐based chemotherapy in the analysis along with other MEC regimens as prespecified in the study protocol 12. In all, 52.8% of the patients received AC‐based chemotherapy in the MEC trial, and 30.1% received carboplatin‐based chemotherapy; the remaining patients received a broad range of other MEC agents.…”

NCCN Guidelines Insights: Antiemesis, Version 2.2017

“…Data suggest that carboplatin, although less emetogenic than cisplatin, is perhaps on the higher end of emetogenic potential within the MEC classification. [21][22][23][24] Several trials and a subset analysis have shown benefit in terms of complete response (CR) in the overall and delayed phases with the addition of a neurokinin-1 (NK1) receptor antagonist (RA) to the 2-drug regimen of a 5-HT3 antagonist and dexamethasone for the prevention of CINV associated with carboplatin-based regimens, thereby affirming the higher emetogenic potential of carboplatin. [21][22][23][24] All of the commercially available NK1 RAs have an FDA-approved indication for MEC chemotherapy, but previous versions of the NCCN Guidelines have supported the addition of an NK1 RA only for select patients receiving MEC with additional CINV risk factors or in those for whom previous therapy with a steroid and 5-HT3 antagonist alone failed.…”

“…UC San Diego Moores Cancer Center; 22 UCSF Helen Diller Family Comprehensive Cancer Center; 23 St. Jude Children's Research Hospital/The University of Tennessee Health Science Center; 24 Memorial Sloan Kettering Cancer Center; 25 Roswell Park Cancer Institute; 26 University of Michigan Comprehensive Cancer Center; and 27 National Comprehensive Cancer Network.…”