Neuroendocrine tumor (NET) progression is associated with deterioration in quality of life (QoL). We assessed the impact of 177Lu-DOTATATE treatment on the time to clinically relevant change (deterioration) in health-related QoL (HRQoL). The NETTER-1 trial is an international phase III study in patients with progressive, somatostatin receptor positive midgut NET. Patients were randomized to receive treatment with 177Lu-DOTATATE versus high-dose (60 mg) Octreotide LAR (Oct). EORTC questionnaires QLQC-30 and G.I.NET-21 were assessed during the trial to determine the impact of treatment on HRQoL.
231 patients completed EORTC QLQC-30 and G.I.NET-21 questionnaires at baseline and every 12 weeks thereafter until tumor progression centrally confirmed. QoL scores were converted to a 100-point scale according to EORTC instructions and individual changes from baseline scores were assessed. Time to QoL deterioration (TTD) was defined as the time from randomization to the first QoL deterioration ≥10 points for each patient in the corresponding domain scale. This magnitude of variation was considered clinically relevant. All analyses were conducted on the ITT population.
TTD was significantly longer in the 177Lu-DOTATATE arm (N = 117) vs the control arm (N = 114) for the following domains: global health status (hazard ratio (HR) 0.406; p = 0.0006), physical functioning (HR 0.518; p = 0.0147), role functioning (HR 0.580; p = 0.0298), fatigue (HR 0.621; p = 0.0297), pain (HR 0.566; p = 0.0247), diarrhea (HR 0.473; p = 0.0107), disease related worries (HR 0.572; p = 0.0176) and body image (HR 0.425; p = 0.0058). In the other domains TTD did not reach statistical significance between the arms. Differences in median TTD were clinically significant in several domains: 28.8 months vs. 6.1 months for global health status, and 25.2 months vs. 11.5 months for physical functioning.
This analysis from the NETTER-1 Phase III study demonstrates that 177Lu-DOTATATE provides a significant quality of life benefit for patients with progressive midgut NETs compared to high-dose octreotide, in addition to the meaningful increase in progression-free survival already reported.
Clinical trial identification
Legal entity responsible for the study
NETTER-1 study group and Advanced Accelerator Applications
Advanced Accelerator Applications
M. Lopera Sierra: Advanced Accelerator Applications Chief Medical Officer E. Krenning: Stock ownership. All other authors have declared no conflicts of interest.