Efficacy and Safety of First-Line Everolimus Therapy Alone or in Combination with Octreotide in Gastroenteropancreatic Neuroendocrine Tumors. A Hellenic Cooperative Oncology Group (HeCOG) Study
Anna Koumarianou,
Dimitrios Pectasides,
Georgia-Angeliki Koliou,
Dimitrios Dionysopoulos,
Dionysia Kolomodi,
Christos Poulios,
Maria Skondra,
Joseph Sgouros,
George Pentheroudakis,
Gregory Kaltsas,
George Fountzilas
Affiliations
Anna Koumarianou
Hematology Oncology Unit Fourth Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Attikon University Hospital, 12462 Athens, Greece
Dimitrios Pectasides
Oncology Section, Second Department of Internal Medicine, Hippokration Hospital, 11527 Athens, Greece
Georgia-Angeliki Koliou
Section of Biostatistics, Hellenic Cooperative Oncology Group, Data Office, 11526 Athens, Greece
Dimitrios Dionysopoulos
Department of Medical Oncology, Papageorgiou Hospital, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, 56403 Thessaloniki, Greece
Dionysia Kolomodi
First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Medical School, Laiko University Hospital, 11527 Athens, Greece
Christos Poulios
Department of Pathology, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, 54006 Thessaloniki, Greece
Maria Skondra
Oncology Section, Second Department of Internal Medicine, Hippokration Hospital, 11527 Athens, Greece
Joseph Sgouros
Third Department of Medical Oncology, Agii Anargiri Cancer Hospital, 14564 Athens, Greece
George Pentheroudakis
Department of Medical Oncology, Medical School, University of Ioannina, 45110 Ioannina, Greece
Gregory Kaltsas
First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Medical School, Laiko University Hospital, 11527 Athens, Greece
George Fountzilas
Aristotle University of Thessaloniki, 54006 Thessaloniki, Greece
The purpose of this study was to explore the efficacy and safety of everolimus administered as a first-line treatment in newly diagnosed patients with metastatic or inoperable gastroenteropancreatic neuroendocrine tumors (GEP NETs). This phase II, multicenter, single-arm study included patients with well-differentiated GEP NETs and a Ki67 < 20%. Everolimus, at 10 mg/day, was administered until disease progression; 18 patients (72%) concomitantly received octreotide long-acting release (LAR), at 30 mg/month. The primary endpoint was the 15-month progression-free survival (PFS) rate. Twenty-five patients (grade 1: 11 patients, grade 2: 14 patients) were enrolled between August 2012 and October 2015. At a median follow-up of 58.1 months, the median PFS was 14.6 months, while the 15-month PFS rate was 48%; median overall survival had not been reached yet. Normal baseline chromogranin A (<4 nmol/l) confirmed a longer PFS (HR = 0.25, 95% CI 0.08−0.77, p = 0.016). Seven patients (28%) achieved an objective response (one complete response and six partial responses) in a median of 2.6 months. Twenty-three grade 3−4 events were recorded (14 patients). No fatal reactions occurred. This prospective phase II study unravels the notable activity of everolimus as a first-line treatment in patients with GEP NETS and contributes valuable information about the high activity of the combination of everolimus and octreotide LAR in this setting. Clinical trial information: NCT01648465.
