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Article Dans Une Revue Neuroendocrinology Année : 2018

Clinical and Biomarker Evaluations of Sunitinib in Patients with Grade 3 Digestive Neuroendocrine Neoplasms

Anna Pellat
  • Fonction : Auteur
Chantal Dreyer
  • Fonction : Auteur
Camille Couffignal
  • Fonction : Auteur
Catherine Lombard-Bohas
  • Fonction : Auteur
Patricia Niccoli
  • Fonction : Auteur
Jean François Seitz
  • Fonction : Auteur
Olivia Hentic
  • Fonction : Auteur
Thierry André
  • Fonction : Auteur
Romain Coriat
  • Fonction : Auteur
Sandrine Faivre
  • Fonction : Auteur
Magaly Zappa
  • Fonction : Auteur
Philippe Ruszniewski
  • Fonction : Auteur
Nicolas Pote
  • Fonction : Auteur
Anne Couvelard
  • Fonction : Auteur
Eric Raymond
  • Fonction : Auteur

Résumé

Background/Aims: Angiogenesis is extensively developed in well-differentiated pancreatic neuroendocrine tumours (PanNET) where sunitinib was shown to prolong progression-free survival, leading to nationwide approval. However, clinical experience in patients with grade 3 gastroenteropancreatic neuroendocrine neoplasms (GEPNEN-G3) remains limited. This prospective phase II trial evaluated potential predictive biomarkers of sunitinib activity in patients with advanced GEPNEN-G3. Methods: Sunitinib was given at a dose of 37.5 mg/day as a continuous daily dosing until progression or unacceptable toxicity. Evaluation of activity was based on RECIST1.1. Safety was evaluated according to NCI-CTCAE v4. Pharmacokinetics of sunitinib and its main active metabolite SU12662 were evaluated. All tumour samples were reviewed histologically for tumour differentiation. PDGFRβ, carbonic anhydrase 9, Ki-67, VEGFR2, and p-AKT were quantified using immunohistochemistry and their expression correlated with response by RECIST1.1. Results: Thirty-one patients were included and 26 had available histological tissue. Six and 20 patients presented well-differentiated tumours (NET-G3) and neuroendocrine carcinoma (NEC), respectively. Eighteen patients responded to sunitinib (4 experienced partial responses and 14 tumour stabilization). A high p-AKT expression correlated with lower response to sunitinib (OR 0.94, 95% CI 0.89–0.99, p = 0.04). Safety and PK exposure to sunitinib and SU12662 in these patients were consistent with that reported in PanNET. Conclusion: Sunitinib showed evidence of activity in patients with GEPNEN-G3 with expected toxicity profile. In the NET-G3 and NEC groups, 4/6 and 11/20 patients were responders, respectively. High p-AKT expression predicted a lower response to sunitinib. Our study allowed the identification of a potential biomarker of resistance/sensitivity to sunitinib in aggressive GEPNEN-G3.
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Dates et versions

hal-04495727 , version 1 (08-03-2024)

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Paternité - Pas d'utilisation commerciale - Pas de modification

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Anna Pellat, Chantal Dreyer, Camille Couffignal, Thomas Walter, Catherine Lombard-Bohas, et al.. Clinical and Biomarker Evaluations of Sunitinib in Patients with Grade 3 Digestive Neuroendocrine Neoplasms. Neuroendocrinology, 2018, 107 (1), pp.24-31. ⟨10.1159/000487237⟩. ⟨hal-04495727⟩
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