Advances in the Treatment of Gastroenteropancreatic Neuroendocrine Carcinomas: Are we Moving Forward?

Abstract Poorly differentiated gastroenteropancreatic neuroendocrine carcinomas are aggressive neoplasms of challenging clinical management. A small proportion of patients with early-stage disease may achieve long-term survival, but the majority of patients present with rapidly lethal metastatic dis...

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Bibliographic Details
Published in:Endocrine reviews 2023-08, Vol.44 (4), p.724-736
Main Authors: Garcia-Carbonero, Rocio, Anton-Pascual, Beatriz, Modrego, Andrea, del Carmen Riesco-Martinez, Maria, Lens-Pardo, Alberto, Carretero-Puche, Carlos, Rubio-Cuesta, Beatriz, Soldevilla, Beatriz
Format: Article
Language:English
Subjects:
Cancer
Carcinoma
Carcinoma, Neuroendocrine - metabolism
Carcinoma, Neuroendocrine - pathology
Chemotherapy
Clinical trials
Cytotoxicity
Development and progression
Drug therapy
Epidemiology
Etoposide
Health aspects
Health services
Humans
Immunotherapy
Ipilimumab
Irinotecan
Lung cancer
Lung Neoplasms
Medical care
Medical prognosis
Metastases
Metastasis
Microsatellite instability
Neoplasms
Neuroendocrine tumors
Neuroendocrine Tumors - diagnosis
Neuroendocrine Tumors - drug therapy
Pancreatic Neoplasms - drug therapy
Pancreatic Neoplasms - genetics
Patients
Platinum
Prognosis
Quality management
Ret protein
Review
Small Cell Lung Carcinoma
Survival
Tumors
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Summary:Abstract Poorly differentiated gastroenteropancreatic neuroendocrine carcinomas are aggressive neoplasms of challenging clinical management. A small proportion of patients with early-stage disease may achieve long-term survival, but the majority of patients present with rapidly lethal metastatic disease. Current standard of care still follows the treatment paradigm of small cell lung cancer, a far more common G3 neuroendocrine neoplasm, although emerging molecular and clinical data increasingly question this approach. In this article, we will briefly summarize epidemiology and prognosis of gastroenteropancreatic neuroendocrine carcinomas to emphasize the very low incidence, aggressive nature, and orphan status of this tumor entity. We will also discuss the current pathological classification and its limitations, as well as recent data on their differential biological background compared with small cell lung cancer, and its potential implications for patients care. Then, we will review the standard of care of systemic therapy, basically focused on platinum-based cytotoxic chemotherapy, including some recent randomized trials providing evidence regarding efficacy of irinotecan vs etoposide platinum doublets. Finally, we will present a comprehensive overview of novel therapeutic strategies in current clinical development, including recently reported data on immunotherapy, tumor-agnostic therapies (microsatellite instability, high tumor mutational burden, NTRK and RET gene fusions, BRAF or KRAS inhibitors), and additional treatment strategies targeting other tumor vulnerabilities (ie, Notch pathway, novel targets for radioligand therapy), and provide some insights regarding unmet needs and future perspectives to improve patient's care and prognosis. Graphical Abstract Graphical Abstract
ISSN:0163-769X
1945-7189
DOI:10.1210/endrev/bnad006