External Validity of Somatostatin Analogs Trials in Advanced Neuroendocrine Neoplasms: The GETNE-TRASGU Study.

INTRODUCTION: Somatostatin analogs (SSA) prolong progression-free survival (PFS) in patients with well-differentiated gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). However, the eligibility criteria in randomized clinical trials (RCTs) have been restricted, which contrasts with the vast heterogeneity found in NENs. METHODS: We identified patients with well-differentiated (Ki-67% ≤20%), metastatic GEP-NENs treated in first line with SSA monotherapy from the Spanish R-GETNE registry. The therapeutic effect was evaluated using a Bayesian Cox model. The objective was to compare survival-based outcomes from real-world clinical practice versus RCTs. RESULTS: The dataset contained 535 patients with a median age of 62 years (range: 26-89). The median Ki-67% was 4 (range: 0-20). The most common primary tumor sites were as follows: midgut, 46%; pancreas, 34%; unknown primary, 10%; and colorectal, 10%. Half of the patients received octreotide LAR (n = 266) and half, lanreotide autogel (n = 269). The median PFS was 28.0 months (95% CI: 22.1-32.0) for octreotide versus 30.1 months (95% CI: 23.1-38.0) for lanreotide. The overall hazard ratio for lanreotide versus octreotide was 0.90 (95% credible interval: 0.71-1.12). The probability of effect sizes >30% with lanreotide versus octreotide was 2 and 6% for midgut and foregut NENs, respectively. CONCLUSION: Our study evaluated the external validity of RCTs examining SSAs in the real world, as well as the main effect-modifying factors (progression status, symptoms, tumor site, specific metastases, and analytical data). Our results indicate that both octreotide LAR and lanreotide autogel had a similar effect on PFS. Consequently, both represent valid alternatives in patients with well-differentiated, metastatic GEP-NENs.

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

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.