Triple Regimen With Fosaprepitant ‘New Standard Of Care’ For Chemoradiotherapy-Induced Emesis

Addition of fosaprepitant to palonosetron and dexamethasone reduces chemoradiotherapy-induced emesis and nausea in women with cervical cancer

medwireNews: Cervical cancer patients undergoing chemoradiotherapy could receive a significant antiemetic benefit from the addition of the neurokinin (NK)-1 receptor antagonist fosaprepitant to the current standard of care, suggest the results of a placebo-controlled, phase III trial.

The double-blind GAND-emesis trial enrolled 234 previously untreated women with cervical cancer who were scheduled to receive fractionated radiotherapy alongside weekly cisplatin 40 mg/m2 for 5 weeks. Participants were randomly assigned to receive either a single intravenous dose of fosaprepitant 150 mg or placebo, together with palonosetron and dexamethasone just before administration of cisplatin.

A higher proportion of patients in the fosaprepitant than the placebo group had sustained no emesis at 5 weeks, with rates of 65.7% versus 48.7%. And the addition of fosaprepitant treatment significantly reduced the cumulative risk of emesis, at a subhazard ratio of 0.58 compared with placebo.

A complete response at 5 weeks – defined as no emesis and no use of rescue antiemetic medication – was also achieved by significantly more fosaprepitant-treated women than those given placebo (24 vs 14%). Moreover, the proportion of patients without nausea during the study period was also higher in the fosaprepitant arm (15 vs 8%).

Christina Ruhlmann, from Odense University Hospital in Denmark, and team write in The Lancet Oncology that “patients receiving fractionated pelvic irradiation and concomitant weekly cisplatin should receive antiemetic prophylaxis with a NK-1 receptor antagonist, palonosetron, and dexamethasone.”

In a linked comment,Lee Schwartzberg, from West Cancer Center in Germantown, Tennessee, USA, agrees that the trial provides “high-quality evidence” that the triple regimen is “a new standard of care” for this patient population, and wonders if the results are generalisable to other chemoradiotherapy settings.

“Whether a more heterogeneous population, different chemotherapy, and alternative radiation schedule would yield similar results is unknown”, he writes.

“Given the minimal incremental toxic effects from the antiemetic regimen, it is reasonable to consider extrapolating the data to other higher risk chemoradiation-induced nausea and vomiting settings including upper abdominal radiation with combined chemotherapy for gastric, oesophageal, or pancreatic cancers.”

And indeed the NK-1 receptor antagonist was well tolerated – with the researchers citing a “generally low” incidence of grade 3 side effects, none of which were attributed to the study treatment.

The commentator concludes: “The GAND-emesis trial brings us one step closer to the ultimate goal of delivering complex combined modality chemoradiotherapy regimens without side-effects.”

Reference

Ruhlmann CH, Christensen TB, Dohn LH, et al. Efficacy and safety of fosaprepitant for the prevention of nausea and emesis during 5 weeks of chemoradiotherapy for cervical cancer (the GAND-emesis study): a multinational, randomised, placebo-controlled, double-blind, phase 3 trial. Lancet Oncol 2016; Advance online publication 4 March. doi: http://dx.doi.org/10.1016/S1470-2045(15)00615-4

Schwartzberg L. Progress in chemoradiotherapy-induced nausea and vomiting. Lancet Oncol 2016; Advance online publication 4 March. doi: http://dx.doi.org/10.1016/S1470-2045(16)00034-6

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