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

Abstract

Introduction: Somatostatin analogues (SSA) prolong progression-free survival (PFS) in patients with well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). However, the eligibility criteria in randomized clinical trials (RCTs) have been restricted, which contrasts with the vast heterogeneity found in NETs. Methods: We identified patients with well-differentiated (Ki67% ≤20%), metastatic GEP-NETs 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 Ki67% was 4 (range: 0-20). The most common primary tumor sites were: 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 vs 30.1 months (95% CI, 23.1-38.0) for lanreotide. The overall hazard ratio for lanreotide vs octreotide was 0.90 (95% credible interval, 0.71-1.12). The probability of effect sizes >30% with lanreotide vs 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.

Advances in the treatment of gastroenteropancreatic neuroendocrine neoplasms with somatostatin analogs

“…GETNE-TRASGU study recruited 535 metastatic, well-differentiated GEP-NETs patients using SSAs monotherapy as the first-line treatment. [15,16] The results showed that the mPFS was 28.7months (95% CI, 23.8–31.1) and the median overall survival (mOS) was 85.9months (95% CI, 71.5–96.7). Meanwhile, predictive factors of SSA as first-line therapy in advanced GEP-NETs were investigated.…”

From biology to clinical practice: antiproliferative effects of somatostatin analogs in neuroendocrine neoplasms

“… 5 , 7 , 8 Reliable comparative data on the efficacy of LAN and OCT are lacking, a Spanish R-GETNE registry study ( n = 535) showed similar effects of LAN-AG and OCT–LAR on PFS [hazard ratio (HR) of 0.9 for LAN versus OCT, 95% confidence interval (CI): 0.71–1.12]. 81 Furthermore, although not systematically studied, there are anecdotal reports that switching between SSA compounds may result in varying degrees of response. 51 , 82 Pharmacologically, OCT and LAN have a similar affinity for SSTR2 (IC 50 0.4 versus 0.75 nmol/L) and SSTR5 (IC 50 5.6 versus 5.2 nmol/L), but their long-acting formulations have different pharmacokinetic profiles (OCT–LAR: prolonged plateau phase for about 30 days after an initial increase and a lag phase; LAN-AG: peak concentration on day 1 and then elimination with a half-life of 25.5 days).…”

“… 84 Apart from lower rates of treatment discontinuation due to AEs with LAN-AG (3% versus 12% in the respective phase III studies), the safety profile is generally comparable. 55 , 68 , 81 , 84 Detailed analyses of the pivotal studies are presented in the following section.…”

Versatile Functions of Somatostatin and Somatostatin Receptors in the Gastrointestinal System

“…Long-acting SST analogues (Octreotide, 20mg/m or Lanreotide, 90mg/28 d, 12months, im) decreased blood transfusion in patients with refractory bleeding from gastrointestinal angiodysplasias (90). SST prolongs progression-free survival (PFS) in individual precision medicine; global multicenter studies have confirmed high dose-SST (Octreotide, 30mg/4ws) (Lanreotide, 120mg/4ws) is an active and safe option in patients with progressive well-differentiated gastroenteropancreatic NETs, and an independent individualized prediction model could be a valuable tool for making treatment decisions in clinical practice for SST-treated patients (91)(92)(93). Therefore, powerful prediction tools, drug-combination, and conjugated-medicine are important to limit the side effects of SST analogues in fatigue, diarrhoea, constipation, abdominal pain, nausea, cholelithiasis and hyperinsulinism, and necrotizing enterocolitis in infants (72,94,95).…”