Relationship Between Best Tumor Shrinkage and Progression-Free Survival and Overall Survival in Patients With Progressive Midgut Neuroendocrine Tumors Treated With [177Lu]Lu-DOTA-TATE: Ad Hoc Analysis of the Phase III NETTER-1 Trial

Abstract

Background: In many solid tumors, early tumor shrinkage predicts the durability of treatment response. It is unclear whether this is the case for neuroendocrine tumors treated with peptide receptor radionuclide therapy (PRRT). Methods: Data from the phase III NETTER-1 study of [177Lu]Lu-DOTA-TATE (177Lu-DOTATATE) for the treatment of advanced, well-differentiated, midgut NETs were used to investigate whether objective tumor shrinkage (local review) with 177Lu-DOTATATE is associated with progression-free survival (PFS) and overall survival (OS) duration. Results: Overall, 117 patients were treated with 177Lu-DOTATATE (four cycles of 7.4 GBq every 8 weeks). In a landmark analysis, best tumor shrinkage from baseline until data cut-off (prior to first progression) was not associated with PFS (n = 102; hazard ratio: 1.002 [95% confidence interval (CI): 0.99–1.02]; nominal p = 0.7808). In further ad hoc analyses, patients on the 177Lu-DOTATATE arm were dichotomized into ≥ 30% tumor shrinkage from baseline (18/117 [15.4%]) and < 30% shrinkage (99/117 [84.6%]). Median (95% CI) PFS was 17.6 (16.5–30.3) months in the ≥ 30% shrinkage group and 25.0 (19.4–31.0) months in the < 30% group. OS was not significantly different for the two tumor shrinkage groups (not estimable [31.0 months–not estimable] and 44.3 [34.9–53.8] months, respectively). Conclusions: These results suggest the benefit of PRRT and the potential PFS and OS benefit of 177Lu-DOTATATE should not be based on tumor shrinkage (objective response versus stable disease) and that lack of tumor shrinkage should not impact application of the approved four cycles of 177Lu-DOTATATE.