Impact of liver tumor burden on therapeutic effect of 177Lu-dotatate treatment in NETTER-1 study

Abstract

Background: The aim of this study was to assess Progression Free Survival (PFS), Safety and Quality of Life (QoL) in subgroups of varying hepatic burden in the NETTER-1 study population. Methods: Patients (pts) were randomized to receive either 177Lu-DOTATATE (Lu)(n = 117) or high-dose octreotide (Oct) (n = 114). The liver tumor burden (LTB) was defined as tumor volume/total liver volume by CT, and categorized as low (<25%), moderate (25-50%), and high (>50%). PFS, QoL and hepatotoxicity were assessed based on baseline LTB. QoL was analysed using EQRTC QLQC 30 and G.I. NET 21 questionnaires completed at baseline and every 12 weeks thereafter for low and moderate/high LTB subgroups. Deterioriation was defined if the score decreased by ≥ 10 points at any time point after baseline. Time to deterioration (TTD) was defined as the time from randomization to the first QoL deterioration. Results: Median PFS (months) in Lu vs Oct was 28.35 vs 11.04 in low (HR = 0.218, 95% CI 0.120 to 0.394); Not Reached (NR) vs 8.67 in moderate (HR = 0.202, 95% CI 0.077 to 0.525); 19.38 vs 5.52 in high LTB (HR = 0.193, 95% CI 0.079 to 0.474), respectively. Median TTD (months) for Global Health Status was 28.81 vs 6.11 in low (HR = 0.376, 95% CI 0.196 to 0.720); NR vs 5.98 in moderate/high LTB (HR = 0.453, 95% CI 0.178 to 1.152). In Lu arm, Grade 3/4 (CTCAE v 4.03) AST and ALT toxicities occurred in the low LTB in 2 and 3 patients, and in the high LTB group in 3 and 1 patients, respectively. Grade 3/4 hyperbilirubinemia occurred in one patient from the low LTB and one from the moderate LTB group. All liver function tests abnormalities were resolved without sequela. There were no high grade ALT, AST and Biliriubin toxicities in Oct arm. Conclusions:177Lu-DOTATATE treatment demonstrated significant PFS improvement regardless of the extent of baseline liver tumor burden in patients with well-differentiated, metastatic midgut NET. Clinically significant liver function test abnormalities were rare, were not associated with high liver tumor burden, and resolved without sequela. The analysis shows that 177Lu-DOTATATE treatment also provides quality of life benefit regardless of baseline liver tumor burden.