Matching-adjusted indirect treatment comparison of [177Lu]Lu-DOTA-TATE, everolimus and sunitinib in advanced, unresectable gastroenteropancreatic neuroendocrine tumours: Relative effectiveness of [177Lu]Lu-DOTA-TATE in gastroenteropancreatic neuroendocrine tumours

Abstract

Head-to-head comparisons of the efficacy of treatments for gastroenteropancreatic neuroendocrine tumours (GEP-NETs) have not yet been reported. This study used a series of matching-adjusted indirect comparisons to indirectly compare the effectiveness of [¹⁷⁷Lu]Lu-DOTA-TATE to everolimus, sunitinib and best supportive care (BSC) for extending progression-free survival and overall survival in patients with advanced, unresectable gastrointestinal (GI)-NETs and P-NETs. The results of the main analysis suggest that after accounting for differences in key prognostic variables, the hazard of progression was 62% (hazard ratio [HR], 0.38; confidence interval [CI]₉₅ 0.25–0.58) and 65% (HR 0.35 CI₉₅ 0.21–0.59) lower in patients with GI-NETs treated with [¹⁷⁷Lu]Lu-DOTA-TATE than in those treated with everolimus and BSC, respectively. Similarly, the hazard of progression was 64% (HR 0.36 CI₉₅ 0.18–0.70), 54% (HR 0.46 CI₉₅ 0.30–0.71) and 79–87% (HR 0.21 CI₉₅ 0.13–0.32; HR 0.13 CI₉₅ 0.08–0.22) lower in patients with P-NET treated with [¹⁷⁷Lu]Lu-DOTA-TATE than in those treated with sunitinib, everolimus and BSC, respectively. The hazard of death was 58% (HR 0.42 CI₉₅ 0.25–0.72), 47% (HR 0.53 CI₉₅ 0.33–0.87) and 44–64% (HR 0.56 CI₉₅ 0.36–0.90; HR 0.34 CI₉₅ 0.20–0.57) lower in P-patients with NET treated with [¹⁷⁷Lu]Lu-DOTA-TATE than in those treated with sunitinib, everolimus and BSC, respectively. While our results must be interpreted with caution given the non-randomised nature of the comparisons and the potential for residual confounding, the magnitude of the effect sizes we observe and their consistency across comparators suggest that [¹⁷⁷Lu]Lu-DOTA-TATE may be a more effective treatment option than everolimus, sunitinib and BSC in advanced, unresectable GEP-NETs.