TY - JOUR
T1 - Prediction of response to everolimus in neuroendocrine tumors
T2 - evaluation of clinical, biological and histological factors
AU - Benslama, Noura
AU - Bollard, Julien
AU - Vercherat, Cécile
AU - Massoma, Patrick
AU - Roche, Colette
AU - Hervieu, Valérie
AU - Peron, Julien
AU - Lombard-Bohas, Catherine
AU - Scoazec, Jean Yves
AU - Walter, Thomas
N1 - Publisher Copyright:
© 2016, Springer Science+Business Media New York.
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Objectives Several targeted therapies are available for metastatic neuroendocrine tumours (NETs) but no predictive factor of response to these treatments has been identified yet. Our aim was to identify and evaluate clinical, biological, histological and functional markers of response to everolimus. Methods We retrospectively reviewed 53 patients with NETs treated with everolimus (68 % in clinical trials). Clinical, biological and histological data were analyzed. The functional marker p-p70S6K, a main effector of the mTOR pathway, was studied by immunohistochemistry in 43 cases. Prognostic factors of progression-free survival (PFS) were studied by Kaplan Meier analysis. Results All patients had metastatic and progressive disease before everolimus treatment. Objective response was 9 % and median PFS was 8.1 (4.7–11.5) months. Hypercholesterolemia (HR = 0.13, p < 0.0001) was associated with longer PFS, whereas presence of bone metastases (HR = 3.1, p < 0.001) and overexpression of p-p70S6K by tumor cells (HR = 2.5, p = 0.01) were associated with shorter PFS under everolimus at multivariate analysis. Conclusion Clinical markers are not useful to predict response to everolimus. However, occurrence of hypercholesterolemia under treatment may be an early marker of response. Prospective studies are required to confirm these results and to assess whether p-p70S6K immunostaining is a prognostic or predictive marker of no-response to everolimus.
AB - Objectives Several targeted therapies are available for metastatic neuroendocrine tumours (NETs) but no predictive factor of response to these treatments has been identified yet. Our aim was to identify and evaluate clinical, biological, histological and functional markers of response to everolimus. Methods We retrospectively reviewed 53 patients with NETs treated with everolimus (68 % in clinical trials). Clinical, biological and histological data were analyzed. The functional marker p-p70S6K, a main effector of the mTOR pathway, was studied by immunohistochemistry in 43 cases. Prognostic factors of progression-free survival (PFS) were studied by Kaplan Meier analysis. Results All patients had metastatic and progressive disease before everolimus treatment. Objective response was 9 % and median PFS was 8.1 (4.7–11.5) months. Hypercholesterolemia (HR = 0.13, p < 0.0001) was associated with longer PFS, whereas presence of bone metastases (HR = 3.1, p < 0.001) and overexpression of p-p70S6K by tumor cells (HR = 2.5, p = 0.01) were associated with shorter PFS under everolimus at multivariate analysis. Conclusion Clinical markers are not useful to predict response to everolimus. However, occurrence of hypercholesterolemia under treatment may be an early marker of response. Prospective studies are required to confirm these results and to assess whether p-p70S6K immunostaining is a prognostic or predictive marker of no-response to everolimus.
KW - Everolimus
KW - Hypercholesterolemia
KW - Markers
KW - Neuroendocrine tumours
KW - P-p70S6K
UR - http://www.scopus.com/inward/record.url?scp=84971613772&partnerID=8YFLogxK
U2 - 10.1007/s10637-016-0363-6
DO - 10.1007/s10637-016-0363-6
M3 - Article
C2 - 27230034
AN - SCOPUS:84971613772
SN - 0167-6997
VL - 34
SP - 654
EP - 662
JO - Investigational New Drugs
JF - Investigational New Drugs
IS - 5
ER -