Everolimus in Combination with Octreotide Long-Acting Repeatable in a First-Line Setting for Patients with Neuroendocrine Tumors: A 5-Year Update

Abstract

Background: We previously presented data of this multicentric, phase II study showing that everolimus plus octreotide long-acting repeatable (LAR) for advanced neuroendocrine neoplasms (NENs), in the first line setting, is an active and safe treatment. We now present updated data at 5 years. Methods: Patients with advanced well-differentiated, previously untreated neuroendocrine tumors of the gastroenteropancreatic tract and of the lung received octreotide LAR 30 mg plus everolimus 10 mg/day. The primary endpoint was the objective response rate (ORR). We performed an analysis of “long responder” patients and of time to progression (TTP) and overall survival (OS) at 5 years. Results: Fifty patients were enrolled; the primary tumor site was: pancreas (14 patients), lung (11 patients), ileum (9 patients), jejunum/duodenum (2 patients), and unknown (14 patients). Seventeen (34%) of these patients have received treatment for more than 2 years. The median exposure to study drugs was 519.5 days (range 48-2,024). Currently 3 patients are still in treatment. The ORR (partial response + complete response) was 18% (95% confidence interval [CI] 7.4-28.6): complete response 1 patient (2%), partial response 8 patients (16%), stable disease 37 patients (74%). The median TTP was 33.6 months (95% CI 18.7-41.2) and the median OS was 61.0 months (95% CI 49.8-not reached). Conclusion: In this update of clinical outcome at 5-year follow-up, everolimus plus octreotide has been shown to be active in advanced NENs. The current analysis showed a further prolongation of TTP and a long exposure to the study drug without major side effects in the long term.

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

“…Our study is in line with this study on the efficacy of everolimus in NETs, and demonstrates the potential activity of the combination to achieve tumor shrinkage in treatment-naïve NETs, independently from the presence or absence of functioning syndromes. According to the updates on clinical outcomes at 5-year follow-up in the ITMO study, everolimus plus octreotide was shown to be active, with a median OS of 61.0 months (95% CI 49.8-not reached), without major side effects in the long term [23].…”

Current treatment status in pancreatic neuroendocrine neoplasms

“…More recently, with minimal adverse effects of new drags, combination of two or more agents have been applied to get better result for those advanced P-NETs, such as everolimus and octreotide LAR (88)(89)(90)(91)(92), everolimus and sunitinib (93), combination of bevacizumab, pertuzumab, and octreotide LAR (94), combination of fluorouracil, doxorubicin, and streptozocin (95,96).…”

Systemic treatment of pancreatic neuroendocrine tumors

“…The only study to date that evaluated the combination treatment strategy proposed in the RADIANT I study was by the Italy Trials in Medical Oncology group . This was a phase II study evaluating the efficacy of everolimus with octreotide LAR on neuroendocrine tumours originating from various organs, including 14 patients with pNET.…”