Use of pre-trial EBV titres as a measure of immune status: Further support for independence from health status of immunological response to G17DT in gemcitabine—G17DT combination pancreatic cancer trial patients

Abstract

4108 Background: In a Phase III pancreatic cancer trial combining G17DT with gemcitabine (Gem) vs Gem alone [ASCO 2005, Abstract 4012], a significant survival effect, independent of baseline KPS, was seen in patients with gastrin antibody response (Placebo + Gem 178 days vs 264 for antibody responders > 16U, p = 0.03). A consistent criticism of such analyses of vaccine trials in cancer patients is that the immuno-responders reflect a fitter sub-population. To show that response to G17DT was at least partially independent of health status, pre-trial EBV titres, which can be considered as a marker of immunological status, were shown to be predictive of survival in the placebo group. However, in the G17DT treated group, antibody responders and non-responders had similar distributions of anti EBV titres. Methods: Baseline PC4 patient sera from both Gem alone (placebo) and Gem + G17DT groups were examined for antibodies against EBV by ELISA. The placebo patients were assigned high or low EBV status if they were respectively above or below the mean titre. Kaplan-Meier curves for these sub-populations were compared using the log rank statistic. G17DT-treated patients were grouped into high, low and non-responders. Mean EBV titres of the G17DT subgroups were compared with each other and with the placebo group using the t-test. Results: HighEBV titre was shown to predict improved survival in the placebo arm of the Phase III trial (Gem treatment only, p = 0.049). However, mean EBV titres were similar in high G17DT antibody responders cf non-responders (EBV titre 125 vs 159, p = 0.13) and in placebo patients cf non-responders (160 vs 159, p = 0.98). Conclusions: Pre-trial EBV titre, found to be predictive of survival in pancreatic cancer patients treated with gemcitabine, was similar between G17DT responders and non-responders, adding further weight to the hypothesis that G17DT response is substantially independent of health status. [Table: see text]