Stein Kaasa, MD
Adding fosaprepitant (Emend) to an antiemetic regimen significantly improved emesis control versus standard care in women receiving radiotherapy and cisplatin for cervical cancer, according to results from the phase III GAND-emesis trial presented at the 2015 European Cancer Congress.
Adding the neurokinin-1 receptor antagonist to palonosetron and dexamethasone significantly improved the “sustained no emesis rate” versus the two drugs alone, at 76.7% versus 65.1% (95% CI, 0.38-0.99; P
“Addition of fosaprepitant to palonosetron and dexamethasone provided significantly better control of emesis and nausea over palonosetron and dexamethasone alone in women receiving chemoradiation for cervical cancer,” said lead study author Christina H. Ruhlmann, PhD candidate at Odense University Hospital, Odense, Denmark.
The phase III GAND-emesis trial was an investigator-initiated, multinational, randomized, double-blind, placebo-controlled phase III trial that enrolled 246 chemotherapy- and radiotherapy-naïve women with cervical cancer. Patients with scheduled brachytherapy prior to the fifteenth radiation fraction or with the diagnosis of another concurrent malignancy were excluded. Ruhlmann emphasized that patients experiencing emesis or moderate-to-severe nausea within the 24 hours preceding the first dose of study medication were also precluded from participation.
All patients received a regimen of 5 fractions per week of radiotherapy at 2 Gy to the pelvis, plus antiemetic prophylaxis with intravenous palonosetron at 0.25 mg plus oral dexamethasone at 16 mg prior to the administration of cisplatin at 40 mg/m2 given on day 1 weekly for 5 weeks. Both cohorts also received 8 mg of dexamethasone twice daily on day 2 of each cycle, 4 mg twice daily on day 3, and 4 mg once daily on day 4. The treatment was repeated for 5 weekly cycles. Patients were also allowed additional use of antiemetic rescue medication.
In addition to this regimen, patients were randomized to either 150 mg of intravenous fosaprepitant daily or placebo.
Overall, 234 patients (118 in the fosaprepitant arm and 116 in the control arm) received study medication and were eligible for the efficacy evaluation. Patient baseline characteristics were well matched between groups; all patients received median EBRT dose of Gy 50.
The primary endpoint was the no emesis rate sustained over days 1 through 35, and secondary endpoints were complete response (CR), nausea, and safety. Efficacy assessments were made daily and safety assessments were made on a weekly basis.
The cumulative incidence over the course of the trial was lower with fosaprepitant. During weeks 1, 2, 3, 4, and 5, no emesis was sustained by 86%, 78%, 73%, 69% and 66% of patients receiving added fosaprepitant compared to 78%, 66%, 59%, 53% and 49% of patients receiving antiemetics only (P
= .008), an overall difference of 17%.
CR, defined as no emesis and no use of rescue antiemetics, within 24 hours after initiation of therapy was achieved by 92% of fosaprepitant patients versus 86% of the placebo arm. CR at 120 and 168 hours post therapy was 74% and 71% versus 64% and 59% in the respective cohorts.
At the end of cycle 1 (168 hours) the rates of no nausea were 42% with fosaprepitant compared to 25% with placebo (P
CR over days 1 to 35 was achieved by 51% of fosaprepitant patients versus 33% of placebo patients (P = .005) and no nausea was sustained over the same duration by 14% versus 8% of fosaprepitant and placebo patients, respectively (P
No statistically significant difference was seen between the adverse event (AE) profiles of the cohorts. The most commonly reported (affecting ≥10 patients) AEs were loss of appetite, fatigue, headache, dizziness, hearing impairment, tinnitus and nervous system disorders.
Discussant Stein Kaasa, MD, a palliative care expert and head of the Cancer Clinic at Trondheim University Hospital in Trondheim, Norway, who was not involved in the study, commended the investigators on evaluating fosaprepitant in a radiotherapy study. He remarked that the findings were, “Not only statistically but also clinically significant. Most studies on emesis control are done with chemotherapy, although we know that nausea and vomiting are highly prevalent when radiation is delivered to the abdomen. I congratulate the study authors for addressing this issue.”
Ruhlmann CH, Christensen TB, Dohn LH, et al. Fosaprepitant for the prevention of nausea and emesis during five weeks of chemo-radiotherapy: a multinational randomised, placebo-controlled, double-blind—the GAND-emesis study. Presented at: 2015 European Cancer Congress; September 25-29; Vienna, Austria. Abstract LBA 34.
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