First update on overall survival, progression-free survival, and health-related time-to-deterioration quality of life from the NETTER-1 study: 177Lu-Dotatate vs. high dose octreotide in progressive midgut neuroendocrine tumors.

Abstract

Background: The final per-protocol statistical analysis (cut–off date 24 July 2015) of PFS, the primary endpoint of the NETTER-1 study, showed a significant difference (p < 0.0001) between the treatment arms. Supplemental updated analysis was requested by regulatory authorities for registration purposes. Quality of life (QoL) was analysed one year later, with a cut-off date of 30 June 2016 for time to clinically relevant deterioration (TTD) in health-related QoL (HRQoL). Methods: Overall survival (OS) and PFS were evaluated using Kaplan Meier methodology. HRQoL analysis was based on EORTC QLQC-30 and G.I.NET-21 questionnaires, completed at baseline and every 12 weeks thereafter. TTD was defined as the time from randomization to the first QoL deterioration ≥10 points for each patient in the corresponding domain scale. First OS regulatory update cut-off date was 30 June 2016. Results: At this first update, median OS was 27.4 months in Oct arm and still not reached in Lu arm. PFS at this date showed 30 events in the Lu arm and 78 in the Oct arm (HR: 0.21 CI: 0.14 0.33; p < 0.0001). HRQoL TTD was significantly longer in the Lu arm vs. the Oct arm for global health status (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). Conclusions: This supplemental analysis from the NETTER-1 Phase III study confirms the clinically and statistically meaningful PFS benefit, and still suggests a survival benefit with 177Lu-dotatate. It also demonstrates that 177Lu-dotatate provides a significant quality of life benefit for patients compared to high-dose octreotide. Clinical trial information: NCT01578239.