Safety and efficacy of different lanreotide doses in the treatment of polycystic liver disease: pooled analysis of individual patient data

Abstract

Long-acting lanreotide (LAN) 120 mg every 4 weeks reduces liver volume (LV) in patients with polycystic liver diseases (PCLD). Animal studies demonstrated that the inhibition of hepatic and renal cystogenesis is dose dependent. To investigate the safety and efficacy of two different LAN doses in PCLD patients. The 6-month results of the LOCKCYST I trial, its extension study and the LOCKCYST II trial were pooled. LV at baseline and month 6 was measured by CT-scan and blindly re-analysed by two independent radiologists. The study population [132 treatment periods, age 49 years (IQR: 45-55), 114 women] consisted of three groups. Each received treatment every 4 weeks during 6 months: placebo (n = 26); LAN 90 mg (n = 55) or LAN 120 mg (n = 51). The inter-observer variability and agreement in the calculation of LV were excellent. Severe side effects occurred with placebo, LAN 90 mg and LAN 120 mg in respectively 0%, 7% and 16%. Change in LV's after 6 months in these three groups were respectively: increase of +36 mL [(-45)-(+138)]; decrease of -82 mL [(-285)-(+92)] and decrease of -123 mL [(-312)-(+4)] (Kruskal-Wallis One Way anova on Ranks; P = 0.002). Based on ROC analysis, a reduction of ≥120 mL in LV has a positive predictive value of 64% for improving symptoms (ROC analysis AUC: 0.729; sensitivity 73%, specificity 69%, P < 0.0001). Both LAN 90 mg and LAN 120 mg reduce liver volume. LAN 90 mg has less side effects. This suggests that in case of intolerance to LAN 120 mg, a dose reduction to LAN 90 mg is meaningful.