Rolapitant for prevention of chemotherapy-induced nausea and vomiting after moderately emetogenic chemotherapy or anthracycline and cyclophosphamide regimens: a randomised, active-controlled, double-blind, phase 3 trial
Adding a single rolapitant tablet to the standard two anti-sickness drugs kept 71 percent of patients free of vomiting and rescue medicine in the days after moderately strong chemotherapy, against 62 percent without it.
Overview
Primary publication of rolapitant Study 3 (NCT01500226). A global, randomised, double-blind, active-controlled phase 3 study at 170 cancer centres in 23 countries enrolled patients aged 18 or older who had not previously received moderately or highly emetogenic chemotherapy. Patients were allocated to oral rolapitant 180 mg or matching placebo one to two hours before moderately emetogenic chemotherapy; all received granisetron 2 mg and dexamethasone 20 mg on day 1 and granisetron on days 2 to 3. The primary endpoint was complete response (no emesis or rescue medication) in the delayed phase (more than 24 to 120 hours) in cycle 1, in the modified intention-to-treat population.
Between 5 March 2012 and 6 September 2013, 1,369 patients were randomised (684 rolapitant, 685 active control); 666 per group were analysed. Complete response in the delayed phase was 475 (71 percent) versus 410 (62 percent); odds ratio 1.6 (95 percent CI 1.2 to 2.0; p = 0.0002). Adverse events were similar between groups, with fatigue, constipation and headache the most frequent treatment-related events; grade 3 to 4 neutropenia in cycle 1 was 5 percent versus 3 percent. No serious adverse event was treatment related.
- Delayed-phase complete response 71 percent with rolapitant vs 62 percent with active control (odds ratio 1.6, 95 percent CI 1.2 to 2.0; p = 0.0002).
- 1,369 patients randomised; 666 per arm in the modified intention-to-treat efficacy population.
- Adverse events similar between arms; grade 3 to 4 neutropenia in cycle 1 5 percent vs 3 percent; no treatment-related serious adverse event.
Together with the two cisplatin studies, this trial supported the September 2015 US approval of rolapitant for delayed nausea and vomiting. Its long half-life means one tablet covers the delayed phase, and unlike aprepitant it does not need a dexamethasone dose adjustment.
- The active control was granisetron plus dexamethasone with placebo, so the trial tests adding rolapitant, not rolapitant against another NK1 antagonist.
- The efficacy population excludes patients treated at sites later found non-compliant with Good Clinical Practice.
- Funded by Tesaro; the product is now marketed by TerSera.