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Single dose of Opko Health's Rolapitant with standard anti-emetic therapy "provides protection for the entire at-risk period" for CINV

Rolapitant Effective Add-on Prophylactic for Chemo-Induced Emesis

Medscape
By Reuters Staff
August 21, 2015

NEW YORK (Reuters Health) – A single oral dose of the investigational anti-emetic rolapitant (Tesaro) helps prevent chemotherapy-induced nausea and vomiting (CINV) when combined with granisetron and dexamethasone, the current standard of care for CINV, according to results of three large phase 3 randomized controlled studies.

Rolapitant is a potent, highly-selective long-acting neurokinin-1 (NK-1) receptor antagonist currently under review at the US Food and Drug Administration.

Findings from the three multinational studies funded by Tesaro appeared online August 11 in Lancet Oncology. Two of the studies involved more than 1000 cancer patients receiving cisplatin-based highly emetogenic chemotherapy and one involved more than 1300 cancer patients receiving moderately emetogenic chemotherapy or anthracycline and cyclophosphamide regimens.

In both trials, patients received a single dose of rolapitant or identical placebo plus standard granisetron and dexamethasone before chemotherapy. The primary endpoint of both trials was patient-reported complete control of emesis and no need for rescue medication in acute (zero to 24 hours after treatment) and delayed (>24 to 120 hours) phases of emesis.

In the moderately emetogenic trial, significantly more patients receiving rolapitant than placebo had complete responses in the delayed phase (475 patients, 71% vs 410 patients, 62%; odds ratio 1.6, P=0.0002), the investigators report.

The same was true in the two highly emetogenic trials. Based on pooled data from the trials, 382 patients (71%) in the rolapitant arm had a complete response in the delayed phase, compared with 322 patients (60%) in the placebo arm (OR 1.6; P=0.0001).

These two studies show that a single dose of rolapitant with standard anti-emetic therapy “provides protection for the entire at-risk period” for CINV, write the investigators, led by Dr Bernardo Rapoport, of the Medical Oncology Centre of Rosebank, Johannesburg, South Africa.

“These trials are among the first to show that addition of an NK-1 receptor antagonist to a 5-HT3 receptor antagonist and a steroid improves prevention of CINV more than 24 h after treatment with moderately emetogenic chemotherapy,” notes Dr. Ian Olver, of the Sansom Institute for Cancer Research, University of South Australia in Adelaide, in a Comment published with the studies.

There was “less consistency” in the acute phase CINV in the moderately emetogenic trial and one of the highly emetogenic studies failed to show a difference between treatment groups in acute emesis, he points out, “although with better control than placebo over the whole 120 h at-risk period. This benefit in delayed emesis is achieved without any relevant additional toxicity.”

Dr. Olver says rolapitant “represents the next generation of NK-1 receptor antagonists, with a long half-life and NK-1 receptor binding for up to five days, suggesting that it will also have a longer duration of action. One advantage of rolapitant over other NK-1 receptor antagonists is that it is not metabolized by CYP3A4, “thereby reducing the chance for possible drug-drug interactions.”

While these three studies show that rolapitant “adds efficacy, particularly in the delayed phase of emesis with moderately and highly emetogenic chemotherapy, rolapitant’s place in routine antiemetic care is yet to be determined,” Dr. Olver concludes.

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