The GAND-emesis trial, a multinational, randomised, double-blind, placebo-controlled phase III trial, in women with cervical cancer receiving fractionated radiotherapy and weekly cisplatin 40 mg/m2, demonstrated an increase of 17% in the proportion of patients completing five weeks of treatment without vomiting when fosaprepitant (FOS) was added to palonosetron (PAL) and dexamethasone (DEX) (Ruhlmann et al, Lancet Oncol, 2016). As a secondary endpoint we investigated whether there was any difference in impairment of daily functional life between groups as a result of nausea or vomiting.
The validated Functional Living Index – Emesis (FLIE) questionnaire consists of 18-items to measure the impact of nausea (9 items domain) and vomiting (9 items domain) on daily functional life. The FLIE-questionnaire was completed at baseline and again at end of study (EoS). The scores for each domain and the total score were calculated according to the FLIE Manual. Domain scores ≥ 54 and total score ≥ 108 indicate no or minimal impact on daily life. The Kruskal-Wallis H test was used to test the difference between groups.
Two hundred and thirty-four patients from four countries were randomised and received study medication. Nine patients were excluded due to invalid questionnaires. Included were 115 patients receiving FOS and 110 patients receiving placebo (PLA). The point scores at baseline were similar across groups (FOS vs PLA); nausea domain: 59.9 vs 60.3 (p = 0.31); vomiting domain: 61.9 vs 62.1 (p = 0.16); and total score: 121.8 vs 122.4 (0.37). At EoS, a statistically significant difference was demonstrated for the point scores for the nausea domain and the total score (FOS vs PLA); nausea domain: 54.9 vs 53 (p = 0.02); vomiting domain: 61.4 vs 60.9 (p = 0.10); and total score: 116.3 vs 113.9 (p = 0.01).
This is the first study to investigate safety, efficacy, and impact on daily function of a neurokinin-1 receptor antagonist during the entire course of concomitant chemo-radiotherapy. The addition of FOS to PAL and DEX not only improved emetic control but also gave a clinically and statistically significant reduction of the impact of nausea on patients’ daily functional life.
Clinical trial identification
EudraCT number: 2009-014691-21. ClinicalTrials.gov: NCT 01074697.
Legal entity responsible for the study
Sponsors delegate and coordinating investigator Christina H. Ruhlmann/for sponsor Prof. Jørn Herrstedt, Odense University Hospital
unrestricted grants from Biovitrum and Helsinn Healthcare S.A.
F. Hilpert: Grants from Riemser Pharma during the conduct of the study. P. Feyer: Grants from Riemser Pharma during the conduct of the study; advisory consultant for MSD, outside the submitted work. D. Keefe: Grants from Helsinn, other from Merck, outside the submitted work J. Herrstedt: Unrestricted grant from Helsinn Healthcare, and an unrestricted grant from SOBI, during the conduct of the study; personal fees from Tesaro outside the submitted work. All other authors have declared no conflicts of interest.