Biological Toxicity can be a Surrogate Marker of Efficacy in Patients (PTS) Treated with MTOR Inhibitors (MTORI) for MRCC

ABSTRACT Background Biological toxicities of mTORi are well characterized. We investigate retrospectively if there is a link between biological toxicities and mTORi efficacy. Patients and methods Biological toxicities were retrospectively collected in patients treated with an mTORi (Everolimus [Ev], Temsirolimus [Tem]) for mRCC at the European G. Pompidou Hospital in Paris, France between 2007 and 2011. Only pts having received mTORi for at least 28 days were eligible. Lymphocytes, creatinaemia, glycaemia, phosphoraemia, liver transaminases, cholesterolaemia, and triglyceridaemia were recorded with onset date and higher grade (NCI-CTC 3.0). Time to onset and onset velocity defined as the absolute change from baseline (%) divided by the time to onset were calculated for each adverse event. Efficacy was assessed with time to progression (TTP) from the initiation of mTORi until disease progression/death and objective response according to RECIST criteria 2.0. Kaplan-Meier estimates with log-rank test were used to compare categorical data and Cox model for continuous data and hazard ratios. Results 75 pts were included. Median age = 56 y (37-86), sex ratio = 4/1 (M/F), pts on Ev (N = 44)/Tem (N = 31) according to setting: 1st = 2/6, 2nd = 9/11, 3rd = 14/9, ≥4th = 20/4. 10 pts on Ev had a dose reduction. Objective response: PR = 6, SD = 40, PD = 20. 7 patients discontinued due to toxicity and 2 for personal decision. Median follow-up time = 22.8 mo. Median TTP = 7.3 mo (95% CI, 4.7-10.8). Hyperglycaemia and hypophosphoraemia are less important in progressors (P  Conclusions Lymphocytopaenia, hyperglycaemia, hypophosphoraemia, and hypertriglyceridaemia were significantly related to objective response or TTP. These events, together with their onset velocity, should be prospectively monitored to investigate their predictive value for efficacy. Disclosure All authors have declared no conflicts of interest.