Fosaprepitant Combination Reduces Risk of Emesis During Chemoradiotherapy for Cervical Cancer
The addition of fosaprepitant (Emend) to palonosetron and dexamethasone reduced the risk of emesis during 5 weeks of chemoradiotherapy for cervical cancer, according to the phase III GAND-emesis trial reported in The Lancet Oncology by Ruhlmann et al.
Study Details
In the double-blind trial, 234 evaluable patients (of 246 total) from Germany, Australia, Norway, and Denmark were randomized to receive single intravenous (IV) doses of fosaprepitant at 150 mg (n = 118) or saline placebo (n = 116) combined with palonosetron at 0.25 mg IV and oral dexamethasone at 16 mg before cisplatin administration during 5 weeks of fractionated radiotherapy and concomitant weekly cisplatin. The primary endpoint was the proportion of patients with sustained no emesis after 5 weeks of treatment, with analysis in the modified intent-to-treat population (all patients who received study medication).
Reduced Risk
The proportion of patients with sustained no emesis at 5 weeks was 65.7% (95% confidence interval [CI] = 42.2%–89.2%) in the fosaprepitant group vs 48.7% (95% CI = 25.2%–72.2%) in the placebo group, with a significantly lower cumulative risk of emesis in the fosaprepitant group (subhazard ratio = 0.58, P = .008). Overall complete response (no emesis and no use of rescue antiemetics) over 5 weeks was observed in 24% vs 14% (P = .007). No nausea over 5 weeks was reported in 15% vs 8% (P = .007).
Adverse Events
The most common grade 1 or 2 adverse events during the 5 weeks of treatment were fatigue (84% vs 87%) and diarrhea (56% in both). The most common grade 3 adverse event was diarrhea (9% vs 5%), with no grade 3 adverse events being considered related to study treatment. Four patients in the fosaprepitant group had infusion-site reactions, and one had infusion-site pain, with no infusion-site adverse events being reported in the placebo group.
The investigators concluded: “To our knowledge, this is the first study to investigate safety and efficacy of a NK-1 [neurokinin 1] receptor antagonist during 5 weeks of radiotherapy and concomitant weekly cisplatin. Patients receiving fosaprepitant in addition to palonosetron and dexamethasone were less likely to experience emesis and nausea compared with those receiving palonosetron and dexamethasone alone. Both treatments were safe and well tolerated. Further investigations in other radiotherapy settings are warranted.”
The study was supported by private and hospital or university funding and grants from Biovitrum and Helsinn Healthcare SA.
Christina H Ruhlmann, PhD, of Odense University Hospital, is the corresponding author of The Lancet Oncology article.
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