Phase II randomized glioma study to evaluate efficacy and satisfaction of rolapitant plus ondansetron in preventing chemoradiation-induced nausea and vomiting

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Abstract Background Nausea and vomiting remain feared cancer treatment-related side-effects. Antiemetic guideline trials exclude malignant glioma patients. In patients receiving radiation with concurrent temozolomide, chemoradiation-induced nausea; vomiting (cRINV) rates are 35%; 26%, respectively, which reduce quality of life, treatment adherence, and cancer control. Methods This randomized phase-II open-label trial, evaluated efficacy, patient preference and satisfaction of ondansetron (short-acting 5HT3-RA; 3h-half-life) monotherapy vs. rolapitant (long-acting NK1-RA; 180h-half-life) plus ondansetron in preventing cRINV during 6-weeks of temozolomide (75 mg/m2/dX42d) with radiation. Fifty-three eligible patients were randomized to Sequence-A (ondansetron-8mg Days:1-42, Day-22 rolapitant-180mg) or Sequence-B (rolapitant Day-1 plus daily ondansetron). Primary endpoint was percentage achieving cRINV-complete response (CR; no vomiting/antiemetic rescue) during the first 2-weeks of radiation. Secondary endpoints: cRIN/cRIV rates, preference/satisfaction for rolapitant/ondansetron, toxicity and adherence. Results Forty-eight (Sequence-A:25; Sequnce-B:23) initiated chemoradiation. Mean age=53, 58% male, 73%, KPS >90%, 73% glioblastoma. During first 2-weeks of radiation, cRINV-CR was 57% with ondansetron and 74% receiving rolapitant/ondansetron (p=0.27). Patient-reported 6-week cRINV-CR was 55% for both arms. First 2-week cRIN rates (38% Sequence-A; 32% Sequence-B) were more than cRIV rates (19% Sequence-A; 0% Sequence-B). Patients receiving ondansetron alone vomited more overall, and the first 2-weeks (26%) than with rolapitant/ondansetron (11%). Among 35 completers, 20% preferred rolapitant/ondansetron, 60% preferred ondansetron, 20% had no preference (p=0.0004). Adverse-events attributable to antiemetics were grade 1-2. Conclusions No difference was found in cRINV-CRs between first 2-week treatments or overall satisfaction. Although not a positive study, less vomiting occurred with rolapitant/ondansetron. While patients prefer ondansetron monotherapy, most perceived better effectiveness with rolapitant/ondansetron.