Efficacy and safety of sunitinib in patients with well-differentiated pancreatic neuroendocrine tumours

Eric Raymond, Matthew H. Kulke, Shukui Qin, Xianjun Yu, Michael Schenker, Antonio Cubillo, Wenhui Lou, Jiri Tomasek, Espen Thiis-Evensen, Jian Ming Xu, Adina E. Croitoru, Mustafa Khasraw, Eva Sedlackova, Ivan Borbath, Paul Ruff, Paul E. Oberstein, Tetsuhide Ito, Liqun Jia, Pascal Hammel, Lin ShenShailesh V. Shrikhande, Yali Shen, Jozef Sufliarsky, Gazala N. Khan, Chigusa Morizane, Salvatore Galdy, Reza Khosravan, Kathrine C. Fernandez, Brad Rosbrook, Nicola Fazio

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: In a phase III study, sunitinib led to a significant increase in progression-free survival (PFS) versus placebo in patients with pancreatic neuroendocrine tumours (panNETs). This study was a post-marketing commitment to support the phase III data. Methods: In this ongoing, open-label, phase IV trial (NCT01525550), patients with progressive, advanced unresectable/metastatic, well-differentiated panNETs received continuous sunitinib 37.5 mg once daily. Eligibility criteria were similar to those of the phase III study. The primary endpoint was investigator-assessed PFS per Response Evaluation Criteria in Solid Tumours v1.0 (RECIST). Other endpoints included PFS per Choi criteria, overall survival (OS), objective response rate (ORR), and adverse events (AEs). Results: Sixty-one treatment-naive and 45 previously treated patients received sunitinib. By March 19, 2016, 82 (77%) patients had discontinued treatment, mainly due to disease progression. Median treatment duration was 11.7 months. Investigator-assessed median PFS per RECIST (95% confidence interval [CI]) was 13.2 months (10.9-16.7): 13.2 (7.4-16.8) and 13.0 (9.2-20.4) in treatment-naive and previously treated patients, respectively. ORR (95% CI) per RECIST was 24.5% (16.7-33.8) in the total population: 21.3% (11.9-33.7) in treatment-naive and 28.9% (16.4-44.3) in previously treated patients. Median OS, although not yet mature, was 37.8 months (95% CI, 33.0-not estimable). The most common treatment-related AEs were neutropenia (53.8%), diarrhoea (46.2%), and leukopenia (43.4%). Conclusions: This phase IV trial confirms sunitinib as an efficacious and safe treatment option in patients with advanced/metastatic, well-differentiated, unresectable panNETs, and supports the phase III study outcomes. AEs were consistent with the known safety profile of sunitinib.

Original languageEnglish
Pages (from-to)237-245
Number of pages9
JournalNeuroendocrinology
Volume107
Issue number3
DOIs
Publication statusPublished - Nov 1 2018

Fingerprint

Neuroendocrine Tumors
Safety
Disease-Free Survival
Confidence Intervals
Therapeutics
Research Personnel
Survival
Leukopenia
sunitinib
Marketing
Neutropenia
Disease Progression
Diarrhea
Placebos
Outcome Assessment (Health Care)
Population
Response Evaluation Criteria in Solid Tumors

Keywords

  • Overall survival
  • Pancreatic neuroendocrine tumour
  • Progression-free survival
  • Safety
  • Sunitinib

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

Cite this

Efficacy and safety of sunitinib in patients with well-differentiated pancreatic neuroendocrine tumours. / Raymond, Eric; Kulke, Matthew H.; Qin, Shukui; Yu, Xianjun; Schenker, Michael; Cubillo, Antonio; Lou, Wenhui; Tomasek, Jiri; Thiis-Evensen, Espen; Xu, Jian Ming; Croitoru, Adina E.; Khasraw, Mustafa; Sedlackova, Eva; Borbath, Ivan; Ruff, Paul; Oberstein, Paul E.; Ito, Tetsuhide; Jia, Liqun; Hammel, Pascal; Shen, Lin; Shrikhande, Shailesh V.; Shen, Yali; Sufliarsky, Jozef; Khan, Gazala N.; Morizane, Chigusa; Galdy, Salvatore; Khosravan, Reza; Fernandez, Kathrine C.; Rosbrook, Brad; Fazio, Nicola.

In: Neuroendocrinology, Vol. 107, No. 3, 01.11.2018, p. 237-245.

Research output: Contribution to journalArticle

Raymond, E, Kulke, MH, Qin, S, Yu, X, Schenker, M, Cubillo, A, Lou, W, Tomasek, J, Thiis-Evensen, E, Xu, JM, Croitoru, AE, Khasraw, M, Sedlackova, E, Borbath, I, Ruff, P, Oberstein, PE, Ito, T, Jia, L, Hammel, P, Shen, L, Shrikhande, SV, Shen, Y, Sufliarsky, J, Khan, GN, Morizane, C, Galdy, S, Khosravan, R, Fernandez, KC, Rosbrook, B & Fazio, N 2018, 'Efficacy and safety of sunitinib in patients with well-differentiated pancreatic neuroendocrine tumours', Neuroendocrinology, vol. 107, no. 3, pp. 237-245. https://doi.org/10.1159/000491999
Raymond, Eric ; Kulke, Matthew H. ; Qin, Shukui ; Yu, Xianjun ; Schenker, Michael ; Cubillo, Antonio ; Lou, Wenhui ; Tomasek, Jiri ; Thiis-Evensen, Espen ; Xu, Jian Ming ; Croitoru, Adina E. ; Khasraw, Mustafa ; Sedlackova, Eva ; Borbath, Ivan ; Ruff, Paul ; Oberstein, Paul E. ; Ito, Tetsuhide ; Jia, Liqun ; Hammel, Pascal ; Shen, Lin ; Shrikhande, Shailesh V. ; Shen, Yali ; Sufliarsky, Jozef ; Khan, Gazala N. ; Morizane, Chigusa ; Galdy, Salvatore ; Khosravan, Reza ; Fernandez, Kathrine C. ; Rosbrook, Brad ; Fazio, Nicola. / Efficacy and safety of sunitinib in patients with well-differentiated pancreatic neuroendocrine tumours. In: Neuroendocrinology. 2018 ; Vol. 107, No. 3. pp. 237-245.
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abstract = "Background: In a phase III study, sunitinib led to a significant increase in progression-free survival (PFS) versus placebo in patients with pancreatic neuroendocrine tumours (panNETs). This study was a post-marketing commitment to support the phase III data. Methods: In this ongoing, open-label, phase IV trial (NCT01525550), patients with progressive, advanced unresectable/metastatic, well-differentiated panNETs received continuous sunitinib 37.5 mg once daily. Eligibility criteria were similar to those of the phase III study. The primary endpoint was investigator-assessed PFS per Response Evaluation Criteria in Solid Tumours v1.0 (RECIST). Other endpoints included PFS per Choi criteria, overall survival (OS), objective response rate (ORR), and adverse events (AEs). Results: Sixty-one treatment-naive and 45 previously treated patients received sunitinib. By March 19, 2016, 82 (77{\%}) patients had discontinued treatment, mainly due to disease progression. Median treatment duration was 11.7 months. Investigator-assessed median PFS per RECIST (95{\%} confidence interval [CI]) was 13.2 months (10.9-16.7): 13.2 (7.4-16.8) and 13.0 (9.2-20.4) in treatment-naive and previously treated patients, respectively. ORR (95{\%} CI) per RECIST was 24.5{\%} (16.7-33.8) in the total population: 21.3{\%} (11.9-33.7) in treatment-naive and 28.9{\%} (16.4-44.3) in previously treated patients. Median OS, although not yet mature, was 37.8 months (95{\%} CI, 33.0-not estimable). The most common treatment-related AEs were neutropenia (53.8{\%}), diarrhoea (46.2{\%}), and leukopenia (43.4{\%}). Conclusions: This phase IV trial confirms sunitinib as an efficacious and safe treatment option in patients with advanced/metastatic, well-differentiated, unresectable panNETs, and supports the phase III study outcomes. AEs were consistent with the known safety profile of sunitinib.",
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author = "Eric Raymond and Kulke, {Matthew H.} and Shukui Qin and Xianjun Yu and Michael Schenker and Antonio Cubillo and Wenhui Lou and Jiri Tomasek and Espen Thiis-Evensen and Xu, {Jian Ming} and Croitoru, {Adina E.} and Mustafa Khasraw and Eva Sedlackova and Ivan Borbath and Paul Ruff and Oberstein, {Paul E.} and Tetsuhide Ito and Liqun Jia and Pascal Hammel and Lin Shen and Shrikhande, {Shailesh V.} and Yali Shen and Jozef Sufliarsky and Khan, {Gazala N.} and Chigusa Morizane and Salvatore Galdy and Reza Khosravan and Fernandez, {Kathrine C.} and Brad Rosbrook and Nicola Fazio",
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TY - JOUR

T1 - Efficacy and safety of sunitinib in patients with well-differentiated pancreatic neuroendocrine tumours

AU - Raymond, Eric

AU - Kulke, Matthew H.

AU - Qin, Shukui

AU - Yu, Xianjun

AU - Schenker, Michael

AU - Cubillo, Antonio

AU - Lou, Wenhui

AU - Tomasek, Jiri

AU - Thiis-Evensen, Espen

AU - Xu, Jian Ming

AU - Croitoru, Adina E.

AU - Khasraw, Mustafa

AU - Sedlackova, Eva

AU - Borbath, Ivan

AU - Ruff, Paul

AU - Oberstein, Paul E.

AU - Ito, Tetsuhide

AU - Jia, Liqun

AU - Hammel, Pascal

AU - Shen, Lin

AU - Shrikhande, Shailesh V.

AU - Shen, Yali

AU - Sufliarsky, Jozef

AU - Khan, Gazala N.

AU - Morizane, Chigusa

AU - Galdy, Salvatore

AU - Khosravan, Reza

AU - Fernandez, Kathrine C.

AU - Rosbrook, Brad

AU - Fazio, Nicola

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Background: In a phase III study, sunitinib led to a significant increase in progression-free survival (PFS) versus placebo in patients with pancreatic neuroendocrine tumours (panNETs). This study was a post-marketing commitment to support the phase III data. Methods: In this ongoing, open-label, phase IV trial (NCT01525550), patients with progressive, advanced unresectable/metastatic, well-differentiated panNETs received continuous sunitinib 37.5 mg once daily. Eligibility criteria were similar to those of the phase III study. The primary endpoint was investigator-assessed PFS per Response Evaluation Criteria in Solid Tumours v1.0 (RECIST). Other endpoints included PFS per Choi criteria, overall survival (OS), objective response rate (ORR), and adverse events (AEs). Results: Sixty-one treatment-naive and 45 previously treated patients received sunitinib. By March 19, 2016, 82 (77%) patients had discontinued treatment, mainly due to disease progression. Median treatment duration was 11.7 months. Investigator-assessed median PFS per RECIST (95% confidence interval [CI]) was 13.2 months (10.9-16.7): 13.2 (7.4-16.8) and 13.0 (9.2-20.4) in treatment-naive and previously treated patients, respectively. ORR (95% CI) per RECIST was 24.5% (16.7-33.8) in the total population: 21.3% (11.9-33.7) in treatment-naive and 28.9% (16.4-44.3) in previously treated patients. Median OS, although not yet mature, was 37.8 months (95% CI, 33.0-not estimable). The most common treatment-related AEs were neutropenia (53.8%), diarrhoea (46.2%), and leukopenia (43.4%). Conclusions: This phase IV trial confirms sunitinib as an efficacious and safe treatment option in patients with advanced/metastatic, well-differentiated, unresectable panNETs, and supports the phase III study outcomes. AEs were consistent with the known safety profile of sunitinib.

AB - Background: In a phase III study, sunitinib led to a significant increase in progression-free survival (PFS) versus placebo in patients with pancreatic neuroendocrine tumours (panNETs). This study was a post-marketing commitment to support the phase III data. Methods: In this ongoing, open-label, phase IV trial (NCT01525550), patients with progressive, advanced unresectable/metastatic, well-differentiated panNETs received continuous sunitinib 37.5 mg once daily. Eligibility criteria were similar to those of the phase III study. The primary endpoint was investigator-assessed PFS per Response Evaluation Criteria in Solid Tumours v1.0 (RECIST). Other endpoints included PFS per Choi criteria, overall survival (OS), objective response rate (ORR), and adverse events (AEs). Results: Sixty-one treatment-naive and 45 previously treated patients received sunitinib. By March 19, 2016, 82 (77%) patients had discontinued treatment, mainly due to disease progression. Median treatment duration was 11.7 months. Investigator-assessed median PFS per RECIST (95% confidence interval [CI]) was 13.2 months (10.9-16.7): 13.2 (7.4-16.8) and 13.0 (9.2-20.4) in treatment-naive and previously treated patients, respectively. ORR (95% CI) per RECIST was 24.5% (16.7-33.8) in the total population: 21.3% (11.9-33.7) in treatment-naive and 28.9% (16.4-44.3) in previously treated patients. Median OS, although not yet mature, was 37.8 months (95% CI, 33.0-not estimable). The most common treatment-related AEs were neutropenia (53.8%), diarrhoea (46.2%), and leukopenia (43.4%). Conclusions: This phase IV trial confirms sunitinib as an efficacious and safe treatment option in patients with advanced/metastatic, well-differentiated, unresectable panNETs, and supports the phase III study outcomes. AEs were consistent with the known safety profile of sunitinib.

KW - Overall survival

KW - Pancreatic neuroendocrine tumour

KW - Progression-free survival

KW - Safety

KW - Sunitinib

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