Everolimus in combination with octreotide long‐acting repeatable in a first‐line setting for patients with neuroendocrine tumors: An ITMO group study

Everolimus is a valid therapeutic option for neuroendocrine tumors (NETs); however, data in a real-world setting outside regulatory trials are sparse. The aim of this study was to determine everolimus tolerability and efficacy, in relation to previous treatments, in a compassionate use program. A total of 169 patients with advanced progressive NETs treated with everolimus were enrolled, including 85 with pancreatic NETs (pNETs) and 84 with nonpancreatic NETs (non-pNETs). Previous treatments included somatostatin analogs (92.9%), peptide receptor radionuclide therapy (PRRT; 50.3%), chemotherapy (49.7%), and PRRT and chemotherapy (22.8%). Overall, 85.2% of patients experienced adverse events (AEs), which were severe (grade 3-4) in 46.1%. The most frequent severe AEs were pneumonitis (8.3%), thrombocytopenia (7.7%), anemia (5.3%), and renal failure (3.5%). In patients previously treated with PRRT andchemotherapy, a12-foldincreased riskforseveretoxicitywas observed, with grade 3-4 AEs reported in 86.8% (vs. 34.3% in other patients). In addition, 63.3% of patients required temporarily everolimus discontinuation due to toxicity. Overall, 27.8% of patients died during a median follow-up of 12 months. Median progression-free survival (PFS) and overall survival (OS) were 12 months and 32 months, respectively. Similar disease control rates, PFS,and OS werereported in pNETs and non-pNETs. In the real-world setting, everolimus is safe and effective for the treatment of NETs of different origins. Higher severe toxicity occurred in patients previously treated with systemic chemotherapy and PRRT. This finding prompts caution when using this drug in pretreated patients and raises the issue of planning for everolimus before PRRT and chemotherapy in the therapeutic algorithm for advanced NETs. The Oncologist 2014;19:966-974 Implications for Practice: Data reported outside regulatory trial settings are useful for physicians dealing with neuroendocrine tumors (NETs) and provide understanding of whether the findings obtained in those trials are consistent with clinical practice. In this real-world study of everolimus in advanced, progressive NETs, significantly higher severe toxicity was observed in patients with long-duration disease and in those previously treated with systemic chemotherapy and/or peptide receptor radionuclide therapy. These findings may help physicians to plan an optimal therapeutic strategy for these patients to avoid predictable severe toxicity that may also result in limitations for further treatments.

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“…Data on 50 naïve advanced NETs showed a single grade 4 AE in 1 patient and no report of grade 3-4 thrombocytopenia or pneumonitis [23].…”

Section: Discussionmentioning

confidence: 93%

Real-World Study of Everolimus in Advanced Progressive Neuroendocrine Tumors

et al. 2014

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“…Indeed, treatment duration with everolimus was longer for patients who were naïve to chemotherapy, thus suggesting that it was better tolerated in the chemonaïve group. The ITMO study group (Bajetta et al 2014) suggests that combined therapy with everolimus/octreotide LAR can be effective as the first line for patients with NETs. The two studies are obviously not comparable, both for the different sample size and for the design of the study.…”

Section: Discussionmentioning

confidence: 99%

“…They also specified that, among patients with pNETs, 2 partial responses (PR) were observed, while none showed a complete response (CR). As for the secondary endpoints [Time To Progression (TTP), and Overall Survival (OS)], no significant differences were observed after a median of 227 days (Bajetta et al 2014). Even with the limitations of the study, such as the low number of subjects and the lack of a control group, the ITMO study Group suggests that combined therapy with everolimus/octreotide LAR can be effective as first line for patients with pNETs as well as with NETs of other origin.…”

Section: Published Prospective Studiesmentioning

confidence: 93%

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Everolimus as first line therapy for pancreatic neuroendocrine tumours: current knowledge and future perspectives

Gallo

Malandrino

Fanciulli

et al. 2017

J Cancer Res Clin Oncol

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Results We identified eight retrospective published studies, two prospective published studies, and five registered clinical trials. Moreover, we analyzed the content of four widespread international guidelines. Conclusions Our critical review confirms the lack of highquality data to recommend everolimus as the first line therapy for pNETs. The ongoing clinical trials reported in this review will hopefully help clinicians, in the near future, to better evaluate the role of everolimus as the first line therapy for pNETs. However, at the moment, there is already enough evidence to recommend everolimus as the first line therapy for patients with symptomatic malignant unresectable insulin-secreting pNETs, to control the endocrine syndrome regardless of tumour growth.

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“…A recent multicenter Italian study on the compassionate use of everolimus in advanced NETs highlighted the increasing risk of severe toxicity in patients who had been previously treated with PRRT or chemotherapy, thus suggesting the early use of everolimus in patients with advanced NETs. [22] Furthermore, Bajetta et al [23] treated patients with everolimus in combination with octreotide LAR as first line approach in advanced NETs and showed that in this setting, this combination treatment is very effective with disease control being reached in 92% of patients. This therapy also has an excellent safety profile, with only one single grade 4 adverse event in the population of 50 patients enrolled.…”

Section: Peptide Receptors Radionuclide Therapy (Prrt)mentioning

confidence: 99%

Controversies in the treatment of digestive neuroendocrine tumors

Rinzivillo¹,

Panzuto²,

Fave³

2016

JCMT

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Gastroenteropancreatic neuroendocrine tumors (NETs) have an incidence of 2.39 per 100,000 inhabitants per year, and a prevalence of 35 cases per 100,000 inhabitants; the gap between these rates is due to the relatively long survival time of these tumors, which can be thus considered as chronic oncological diseases. Recently, more therapeutic options have become available, but criteria for defining timing, priority and sequence of different therapeutic options are still debated. This review offers an overview of pancreatic and small bowel NETs, critically underlining the issues that still need to be clarified and some controversial issues on the therapeutic approach for NET patients.

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Everolimus in combination with octreotide long‐acting repeatable in a first‐line setting for patients with neuroendocrine tumors: An ITMO group study

Cited by 67 publications

References 33 publications

Real-World Study of Everolimus in Advanced Progressive Neuroendocrine Tumors

Real-World Study of Everolimus in Advanced Progressive Neuroendocrine Tumors

Everolimus as first line therapy for pancreatic neuroendocrine tumours: current knowledge and future perspectives

Controversies in the treatment of digestive neuroendocrine tumors

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