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

Mohid S. Khan; Elaine Stamp; Cormac Sammon; Tessa Brabander; Wouter W. de Herder; Marianne E. Pavel

doi:10.1016/j.ejcsup.2021.06.002

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

Mohid S. Khan^*, Elaine Stamp, Cormac Sammon, Tessa Brabander, Wouter W. de Herder, Marianne E. Pavel

^*Corresponding author for this work

Internal Medicine

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Pages (from-to)	5-13
Number of pages	9
Journal	European Journal of Cancer, Supplement
Volume	16
DOIs	https://doi.org/10.1016/j.ejcsup.2021.06.002
Publication status	Published - Nov 2021

Bibliographical note

Funding Information:
This article is part of a supplement supported by Advanced Accelerator Applications (AAA), a Novartis company. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M.S.K. has received speaker fees from AAA, Ipsen and Novartis and consultancy fees from Ipsen and Novartis. E.S., C.S., T.B., W.W.d.H. and M.E.P. have no known competing financial interests or personal relationships to declare.

Funding Information:
This article is part of a supplement supported by Advanced Accelerator Applications (AAA), a Novartis company . The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M.S.K. has received speaker fees from AAA, Ipsen and Novartis and consultancy fees from Ipsen and Novartis. E.S., C.S., T.B., W.W.d.H. and M.E.P. have no known competing financial interests or personal relationships to declare.

Publisher Copyright:
© 2021

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Khan, M. S., Stamp, E., Sammon, C., Brabander, T., de Herder, W. W., & Pavel, M. E. (2021). 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. European Journal of Cancer, Supplement, 16, 5-13. https://doi.org/10.1016/j.ejcsup.2021.06.002

Khan, Mohid S. ; Stamp, Elaine ; Sammon, Cormac et al. / 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. In: European Journal of Cancer, Supplement. 2021 ; Vol. 16. pp. 5-13.

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title = "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.",

author = "Khan, {Mohid S.} and Elaine Stamp and Cormac Sammon and Tessa Brabander and {de Herder}, {Wouter W.} and Pavel, {Marianne E.}",

note = "Funding Information: This article is part of a supplement supported by Advanced Accelerator Applications (AAA), a Novartis company. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M.S.K. has received speaker fees from AAA, Ipsen and Novartis and consultancy fees from Ipsen and Novartis. E.S., C.S., T.B., W.W.d.H. and M.E.P. have no known competing financial interests or personal relationships to declare. Funding Information: This article is part of a supplement supported by Advanced Accelerator Applications (AAA), a Novartis company . The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M.S.K. has received speaker fees from AAA, Ipsen and Novartis and consultancy fees from Ipsen and Novartis. E.S., C.S., T.B., W.W.d.H. and M.E.P. have no known competing financial interests or personal relationships to declare. Publisher Copyright: {\textcopyright} 2021",

year = "2021",

month = nov,

doi = "10.1016/j.ejcsup.2021.06.002",

language = "English",

volume = "16",

pages = "5--13",

journal = "European Journal of Cancer, Supplement",

issn = "1359-6349",

publisher = "Elsevier Ltd.",

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Khan, MS, Stamp, E, Sammon, C, Brabander, T , de Herder, WW & Pavel, ME 2021, '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', European Journal of Cancer, Supplement, vol. 16, pp. 5-13. https://doi.org/10.1016/j.ejcsup.2021.06.002

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. / Khan, Mohid S.; Stamp, Elaine; Sammon, Cormac et al.
In: European Journal of Cancer, Supplement, Vol. 16, 11.2021, p. 5-13.

Research output: Contribution to journal › Article › Academic › peer-review

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T1 - Matching-adjusted indirect treatment comparison of [177Lu]Lu-DOTA-TATE, everolimus and sunitinib in advanced, unresectable gastroenteropancreatic neuroendocrine tumours

T2 - Relative effectiveness of [177Lu]Lu-DOTA-TATE in gastroenteropancreatic neuroendocrine tumours

AU - Khan, Mohid S.

AU - Stamp, Elaine

AU - Sammon, Cormac

AU - Brabander, Tessa

AU - de Herder, Wouter W.

AU - Pavel, Marianne E.

N1 - Funding Information: This article is part of a supplement supported by Advanced Accelerator Applications (AAA), a Novartis company. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M.S.K. has received speaker fees from AAA, Ipsen and Novartis and consultancy fees from Ipsen and Novartis. E.S., C.S., T.B., W.W.d.H. and M.E.P. have no known competing financial interests or personal relationships to declare. Funding Information: This article is part of a supplement supported by Advanced Accelerator Applications (AAA), a Novartis company . The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M.S.K. has received speaker fees from AAA, Ipsen and Novartis and consultancy fees from Ipsen and Novartis. E.S., C.S., T.B., W.W.d.H. and M.E.P. have no known competing financial interests or personal relationships to declare. Publisher Copyright: © 2021

PY - 2021/11

Y1 - 2021/11

N2 - 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.

AB - 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.

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Khan MS, Stamp E, Sammon C, Brabander T , de Herder WW, Pavel ME. 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. European Journal of Cancer, Supplement. 2021 Nov;16:5-13. doi: 10.1016/j.ejcsup.2021.06.002