The novel NK-1 receptor antagonist rolapitant reduces nausea and vomiting in patients receiving cisplatin-based chemotherapy
Phase III data presented at ESMO 2014 demonstrate that the novel NK-1 receptor antagonist rolapitant reduces nausea and vomiting in patients receiving cisplatin-based chemotherapy. Chemotherapy-induced nausea and vomiting (CINV) is a common side-effect of this type of chemotherapy and often leads to dose reductions and treatment discontinuation. Rolapitant can make a significant difference in the way patients tolerate their treatment. In fact, patients receiving rolapitant experienced no loss in their quality of life.This is in sharp contrast to many patients on current standard anti-emetics that are too ill to get out of bed within a week after each cycle of cisplatin.
In the presented multi-center, randomized double-blind Phase 3 trial, 532 patients receiving cisplatin-based chemotherapy were randomized 1:1 to receive oral rolapitant + granisetron/dexamethasone (G/D) or placebo + G/D prior to chemotherapy. The primary endpoint of the trial consisted of complete response (CR; no emesis/no rescue medications) in the delayed phase (>24-120 hrs) post-chemotherapy, while key secondary endpoints included CR during acute (0-24 hrs) and overall (0-120 hrs) phases.
The trial met its primary endpoint, with 72.7% of patients receiving rolapitant achieving a complete response in the delayed phase compared to 58.4% of those receiving placebo (p < 0.001). In addition, rolapitant improved the complete response rate compared to placebo in the acute (83.7% vs. 73.7%, p = 0.005) and overall Phases (70.1% vs. 56.5%, p = 0.001). Interestingly, patients receiving rolapitant tended to report that their chemotherapy had less of an impact on their daily quality of life (72.8% vs. 67.8%, p = 0.231) compared to patients in the placebo arm. Treatment emergent AEs were consistent across both arms and generally related to underlying medical condition or chemotherapy.
It is known now that the NK-1 receptor in the brain must be blocked to control nausea and vomiting. In contrast to other agents blocking this receptor, rolapitant is an exceptionally long term receptor blocker that binds to the receptor and remains in place for up to 120 hours, therefore not allowing the chemotherapy to induce nausea and vomiting. These data illustrate the potential of this drug in the management of patients that are treated with cisplatin, possibly the strongest inducer of emesis. Some patients are extremely sensitive to cisplatin effects and these side effects may sometimes make patients refuse a cisplatin-based therapy. Rolapitant offers these patients the possibility to have treatment without compromising their quality-of-life.
Chasen M, Poma A, Hedley M, et al. Phase 3 trial (P04832) results for rolapitant, a novel NK-1 receptor antagonist, in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving cisplatin-based chemotherapy. Presented at ESMO 2014; Abstract LBA47.