Patient-reported outcomes as a component of the primary endpoint in a double-blind, placebo-controlled trial in advanced pancreatic cancer.

Abstract In this randomized, double-blind, placebo-controlled study comparing gemcitabine+tipifarnib (G+t) or gemcitabine+placebo (G+p) in patients with pancreatic cancer, the primary endpoint of time to deterioration (TTD) was based primarily on patient-reported outcomes. Deterioration was defined as death or worsening of disease-related symptoms, based on patient-reported outcomes of pain intensity and analgesic use in a daily diary, plus investigator-rated weekly performance status. Secondary endpoints included survival and safety. Two hundred and forty-four patients were treated for a total of 4780 weeks, during which the diary was completed daily. Overall, the completion of the diary was found to be feasible: patients completed approximately 95% of scheduled diary entries. Baseline characteristics were well balanced between the two treatment arms. The primary endpoint of TTD was not significantly different between the G+t arm (69 days) and the G+p arm (91 days, P =0.40). Survival was not significantly different between the G+t arm (202 days) and the G+p arm (221 days, P =0.66). The combination of G+t had an acceptable toxicity profile, with primarily neutropenia and thrombocytopenia. Methodologically, measurement of patient-reported outcomes is feasible and useful in assessing the effect of anti-cancer therapy in pancreatic cancer if comprehensive initial and ongoing training is provided to all people involved, including not only the patients but also the study personnel.