Safety and efficacy of everolimus in gastrointestinal and pancreatic neuroendocrine tumors after 177Lu-octreotate

Kamp, Kimberly; Gumz, Brenda Pires; Feelders, Richard A; Kwekkeboom, Dik J.; Kaltsas, Gregory; Costa, Frederico; Herder, Wouter W. de

doi:10.1530/erc-13-0254

Cited by 39 publications

(38 citation statements)

References 13 publications

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“…Finally, a longer interval of time between PRRT and everolimus treatment has been reported in comparison with the present study (18 months and 8 months, respectively). Consequently, a reliable comparison between the paper by Kamp et al [20] and other studies is not feasible.…”

Section: Discussionmentioning

confidence: 93%

Real-World Study of Everolimus in Advanced Progressive Neuroendocrine Tumors

et al. 2014

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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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Section: Discussionmentioning

confidence: 93%

Real-World Study of Everolimus in Advanced Progressive Neuroendocrine Tumors

et al. 2014

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“…A population-based retrospective multicenter study from Italy indicated that everolimus use after PRRT and/ or cytotoxic chemotherapy might increase the overall toxicity of everolimus; a smaller retrospective study from the Netherlands, however, reported that the safety profile of everolimus is unaffected by prior PRRT (Panzuto et al 2014, Kamp et al 2013. Sequence of therapies in individual patients may be driven by tumor changes over time.…”

Section: Sequential Therapiesmentioning

confidence: 99%

WOMEN IN CANCER THEMATIC REVIEW: Systemic therapies in neuroendocrine tumors and novel approaches toward personalized medicine

Pavel¹,

Sers²

2016

Endocrine-Related Cancer

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Neuroendocrine tumors (NETs) are a group of heterogenous neoplasms. Evidencebased treatment options for antiproliferative therapy include somatostatin analogues, the mTOR inhibitor everolimus, the multiple tyrosine kinase inhibitor sunitinib and peptide receptor radionuclide therapy with 177-Lu-octreotate. In the absence of definite predictive markers, therapeutic decision making follows clinical and pathological criteria. As objective response rates with targeted drugs are rather low, and response duration is limited in most patients, numerous combination therapies targeting multiple pathways have been explored in the field. Upfront combination of drugs, however, is associated with increasing toxicity and has shown little benefit. Major advancements in the molecular understanding of NET based on genomic, epigenomic and transcriptomic analysis have been achieved with prognostic and therapeutic impact. New insight into molecular alterations has paved the way to biomarker-driven clinical trials and may facilitate treatment stratification toward personalized medicine in the near future. However, an improved understanding of the complexity of pathway interactions is required for successful treatment. A systems biology approach is one of the tools that may help to achieve this endeavor.

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“…According to authors, their findings should raise the issue of planning treatment with everolimus before other options, prompting the use of particular caution in the use of everolimus in heavily pretreated subjects. Conversely, a retrospective analysis by Kamp et al (2013) on 24 patients treated with everolimus showed that the safety profile of the drug was not influenced by the previous PRRT with 177Lu-octreotate (Kamp et al 2013).…”

Section: Discussionmentioning

confidence: 94%

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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Safety and efficacy of everolimus in gastrointestinal and pancreatic neuroendocrine tumors after 177Lu-octreotate

Abstract: Although 177 Lu-octreotate is an effective treatment for patients with gastroentero-

Cited by 39 publications

References 13 publications

Real-World Study of Everolimus in Advanced Progressive Neuroendocrine Tumors

Real-World Study of Everolimus in Advanced Progressive Neuroendocrine Tumors

WOMEN IN CANCER THEMATIC REVIEW: Systemic therapies in neuroendocrine tumors and novel approaches toward personalized medicine

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

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