Prediction of Progression-Free Survival in Patients With Advanced, Well-Differentiated, Neuroendocrine Tumors Being Treated With a Somatostatin Analog: The GETNE-TRASGU Study.

Abstract

PURPOSE:

Somatostatin analogs (SSAs) are recommended for the first-line treatment of most patients with well-differentiated, gastroenteropancreatic (GEP) neuroendocrine tumors; however, benefit from treatment is heterogeneous. The aim of the current study was to develop and validate a progression-free survival (PFS) prediction model in SSA-treated patients.

PATIENTS AND METHODS:

We extracted data from the Spanish Group of Neuroendocrine and Endocrine Tumors Registry (R-GETNE). Patient eligibility criteria included GEP primary, Ki-67 of 20% or less, and first-line SSA monotherapy for advanced disease. An accelerated failure time model was developed to predict PFS, which was represented as a nomogram and an online calculator. The nomogram was externally validated in an independent series of consecutive eligible patients (The Christie NHS Foundation Trust, Manchester, United Kingdom).

RESULTS:

We recruited 535 patients (R-GETNE, n = 438; Manchester, n = 97). Median PFS and overall survival in the derivation cohort were 28.7 (95% CI, 23.8 to 31.1) and 85.9 months (95% CI, 71.5 to 96.7 months), respectively. Nine covariates significantly associated with PFS were primary tumor location, Ki-67 percentage, neutrophil-to-lymphocyte ratio, alkaline phosphatase, extent of liver involvement, presence of bone and peritoneal metastases, documented progression status, and the presence of symptoms when initiating SSA. The GETNE-TRASGU (Treated With Analog of Somatostatin in Gastroenteropancreatic and Unknown Primary NETs) model demonstrated suitable calibration, as well as fair discrimination ability with a C-index value of 0.714 (95% CI, 0.680 to 0.747) and 0.732 (95% CI, 0.658 to 0.806) in the derivation and validation series, respectively.

CONCLUSION:

The GETNE-TRASGU evidence-based prognostic tool stratifies patients with GEP neuroendocrine tumors receiving SSA treatment according to their estimated PFS. This nomogram may be useful when stratifying patients with neuroendocrine tumors in future trials. Furthermore, it could be a valuable tool for making treatment decisions in daily clinical practice.

• Authors: Alberto Carmona-Bayonas, Paula Jiménez-Fonseca, Ángela Lamarca, Jorge Barriuso, Ángel Castaño, Marta Benavent, Vicente Alonso, María Del Carmen Riesco-Martínez, Teresa Alonso-Gordoa, Ana Custodio, Manuel Sánchez Cánovas, Jorge Hernando Cubero, Carlos López, Adelaida Lacasta, Ana Fernández Montes, Mónica Marazuela, Guillermo Crespo, Pilar Escudero, José Ángel Diaz, Eduardo Feliciangeli, Javier Gallego, Marta Llanos, Ángel Segura, Felip Vilardell, Juan Carlos Percovich, Enrique Grande, Jaume Capdevila, Juan W Valle, Rocío García-Carbonero
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 37 Issue 28 Pg. 2571-2580 (10 01 2019) ISSN: 1527-7755 [Electronic] United States
• PMID: 31390276 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hormones
• Somatostatin

Topics

• Adolescent
• Adult
• Cohort Studies
• Female
• Hormones (pharmacology, therapeutic use)
• Humans
• Male
• Neuroendocrine Tumors (drug therapy, mortality, pathology)
• Progression-Free Survival
• Retrospective Studies
• Somatostatin (analogs & derivatives, pharmacology, therapeutic use)
• Survival Analysis
• Young Adult