Rolapitant for the treatment of chemotherapy-induced nausea and vomiting

Abstract

Chemotherapy-induced nausea and vomiting is a significant clinical issue which affects patient’s quality of life and treatment decisions. Significant improvements in the control of chemotherapy-induced nausea and vomiting have occurred in the past 15 years with the introduction of new antiemetic agents 5-HT₃, receptor antagonists, neurokinin-1 (NK-1) receptor antagonists, and olanzapine. Aprepitant was the first NK-1 receptor antagonist introduced (2003) for the prevention of chemotherapy-induced nausea and vomiting in combination with a 5-HT₃ receptor antagonist and dexamethasone. A second NK-1 receptor antagonist netupitant was approved for use in October 2014. Phase III clinical trials of an additional NK-1 receptor antagonist rolapitant have been completed, and the data have been submitted for regulatory approval. A description of rolapitant and its role in chemotherapy-induced nausea and vomiting will be presented, along with a comparison of the other neurolinin-1 receptor antagonists aprepitant and netupitant.

Keywords:

• 5-hydroxytryptamine-3 receptor antagonists
• antiemetics
• aprepitant
• chemotherapy-induced nausea and vomiting
• netupitant
• rolapitant

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Rolapitant is a high-affinity, highly-selective neurokinin-1 (NK-1) receptor antagonist that penetrates the CNS after oral administration.

• Rolapitant has a long half-life of approximately 180 h, a high affinity (K_i = 0.66 nM) for the NK-1 receptor, and does not induce or inhibit CYP3A4.

• A 180-mg dose of rolapitant was used in three large Phase III clinical trials that demonstrated that rolapitant, granisetron and dexamethasone significantly improved complete response compared with granisetron and dexamethasone alone in patients receiving moderately emetogenic chemotherapy and highly emetogenic chemotherapy The results of the Phase III clinical trials have been submitted to the US FDA with a response expected in the third quarter of 2015.

• At present, there are no definitive clinical trials reporting a direct comparison of the efficacy and safety of the various NK-1 receptor antagonists (aprepitant, fosaprepitant, netupitant, rolapitant), but they appear to be comparable in efficacy and safety.

• Based on the available clinical trial data, the NK-1 receptor antagonists have significantly improved the prevention of acute and delayed emesis in patients receiving moderately emetogenic chemotherapy or highly emetogenic chemotherapy. There is little evidence, however, that these agents are effective in controlling nausea.

• At present, the determining factors in the choice of the NK-1 receptor antagonists appear to be cost and the preference for the use of either an oral or an intravenous agent.