CONTEXT: Everolimus, an oral inhibitor of mammalian target of rapamycin, significantly prolongs progression-free survival (PFS) in patients with advanced pancreatic neuroendocrine tumors (pNET). Chromogranin A (CgA) and neuron-specific enolase (NSE) are considered general biomarkers of these tumors. OBJECTIVE: The objective of the study was to evaluate the prognostic value of CgA and NSE in patients with pNET treated with everolimus. PATIENTS AND METHODS: Patients with low- to intermediate-grade advanced pNET enrolled in two phase 2 studies [RAD001 in Advanced Neuroendocrine Tumors (RADIANT-1) and single institution phase II study at The University of Texas M. D. Anderson Cancer Center] received everolimus. Blood samples were collected and analyzed by a central laboratory at baseline and monthly thereafter. PFS and overall survival (OS) were evaluated in patients with elevated and nonelevated baseline CgA/NSE levels. RESULTS: In RADIANT-1, elevated vs. nonelevated baseline CgA was associated with shorter median PFS (8.34 vs. 15.64 months; P = 0.03) and OS (16.95 months vs. not reached; P < 0.001). Elevated vs. nonelevated baseline NSE resulted in shorter median PFS (7.75 vs. 12.29 months; P = 0.01) and OS (13.96 vs. 24.90 months; P = 0.005). Median PFS was prolonged in patients with early CgA or NSE response (11.0 vs. 5.0 months) compared with those without early biomarker response. More patients with CgA (87 vs. 50%) or NSE (81 vs. 14%) response experienced tumor shrinkage compared with those without response. CgA response data from the single-institution phase II study at The University of Texas M. D. Anderson Cancer Center study are consistent with data from the RADIANT-1 study. CONCLUSIONS: Elevated baseline CgA/NSE provided prognostic information on PFS and survival; early CgA/NSE responses are potential prognostic markers for treatment outcomes in patients with advanced pNET.
CONTEXT: Everolimus, an oral inhibitor of mammalian target of rapamycin, significantly prolongs progression-free survival (PFS) in patients with advanced pancreatic neuroendocrine tumors (pNET). Chromogranin A (CgA) and neuron-specific enolase (NSE) are considered general biomarkers of these tumors. OBJECTIVE: The objective of the study was to evaluate the prognostic value of CgA and NSE in patients with pNET treated with everolimus. PATIENTS AND METHODS: Patients with low- to intermediate-grade advanced pNET enrolled in two phase 2 studies [RAD001 in Advanced Neuroendocrine Tumors (RADIANT-1) and single institution phase II study at The University of Texas M. D. Anderson Cancer Center] received everolimus. Blood samples were collected and analyzed by a central laboratory at baseline and monthly thereafter. PFS and overall survival (OS) were evaluated in patients with elevated and nonelevated baseline CgA/NSE levels. RESULTS: In RADIANT-1, elevated vs. nonelevated baseline CgA was associated with shorter median PFS (8.34 vs. 15.64 months; P = 0.03) and OS (16.95 months vs. not reached; P < 0.001). Elevated vs. nonelevated baseline NSE resulted in shorter median PFS (7.75 vs. 12.29 months; P = 0.01) and OS (13.96 vs. 24.90 months; P = 0.005). Median PFS was prolonged in patients with early CgA or NSE response (11.0 vs. 5.0 months) compared with those without early biomarker response. More patients with CgA (87 vs. 50%) or NSE (81 vs. 14%) response experienced tumor shrinkage compared with those without response. CgA response data from the single-institution phase II study at The University of Texas M. D. Anderson Cancer Center study are consistent with data from the RADIANT-1 study. CONCLUSIONS: Elevated baseline CgA/NSE provided prognostic information on PFS and survival; early CgA/NSE responses are potential prognostic markers for treatment outcomes in patients with advanced pNET.
Authors: Wieland H Sommer; Felix Ceelen; Xabier García-Albéniz; Philipp M Paprottka; Christoph J Auernhammer; Marco Armbruster; Konstantin Nikolaou; Alexander R Haug; Maximilian F Reiser; Daniel Theisen Journal: Eur Radiol Date: 2013-06-28 Impact factor: 5.315
Authors: Nancy Sharma; Boris G Naraev; Eric G Engelman; M Bridget Zimmerman; David L Bushnell; Thomas M OʼDorisio; M Sue OʼDorisio; Yusuf Menda; Jan Müller-Brand; James R Howe; Thorvardur R Halfdanarson Journal: Pancreas Date: 2017-02 Impact factor: 3.327
Authors: Marianne E Pavel; Alexandria T Phan; Edward M Wolin; Beloo Mirakhur; Nilani Liyanage; Susan Pitman Lowenthal; George A Fisher; Aaron I Vinik Journal: Oncologist Date: 2018-10-24
Authors: James C Yao; Marianne Pavel; Catherine Lombard-Bohas; Eric Van Cutsem; Maurizio Voi; Ulrike Brandt; Wei He; David Chen; Jaume Capdevila; Elisabeth G E de Vries; Paola Tomassetti; Timothy Hobday; Rodney Pommier; Kjell Öberg Journal: J Clin Oncol Date: 2016-09-30 Impact factor: 44.544