Paula Jimenez-Fonseca1, Alberto Carmona-Bayonas2, Angela Lamarca3,4, Jorge Barriuso3,4, Angel Castaño5, Marta Benavent6, Vicente Alonso7, Maria Del Carmen Riesco8, Teresa Alonso-Gordoa9, Ana Custodio10, Manuel Sanchez Canovas2, Jorge Hernando11, Carlos López12, Adelaida La Casta13, Ana Fernandez Montes14, Mónica Marazuela15, Guillermo Crespo16, Jose Angel Diaz17, Eduardo Feliciangeli18, Javier Gallego19, Marta Llanos20, Angel Segura21, Felip Vilardell22, Juan Carlos Percovich23, Enrique Grande24, Jaume Capdevila11, Juan Valle3,4, Rocio Garcia-Carbonero8. 1. Medical Oncology Department, Hospital Universitario Central de Asturias, ISPA, Oviedo, Spain. 2. Hematology and Medical Oncology Department, Hospital Universitario Morales Meseguer, UMU, IMIB, Murcia, Spain. 3. Medical Oncology Department, The Christie NHS Foundation Trust, ENETS Centre of Excellence, Manchester, United Kingdom. 4. Division of Cancer Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester, United Kingdom. 5. Pathology Department, Hospital Universitario de Fuenlabrada, Madrid, Spain. 6. Medical Oncology Department, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain. 7. Medical Oncology Department, Hospital Universitario Miguel Servet, Zaragoza, Spain. 8. Medical Oncology Department, Hospital Universitario Doce de Octubre, IIS imas12, UCM, CNIO, CIBERONC, Madrid, Spain. 9. Medical Oncology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain. 10. Medical Oncology Department, Hospital Universitario La Paz, CIBERONC CB16/12/00398, Madrid, Spain. 11. Medical Oncology Department, Hospital Universitario Vall d'Hebron, Vall Hebron Institute of Oncology (VHIO), Autonomous University of Barcelona, Barcelona, Spain. 12. Medical Oncology Department, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain. 13. Medical Oncology Department, Hospital Universitario Donostia, San Sebastián, Spain. 14. Medical Oncology Department, Complexo Hospitalario Universitario de Ourense, Ourense, Spain. 15. Endocrinology Department, Hospital Universitario de la Princesa, Madrid, Spain. 16. Medical Oncology Department, Complejo Asistencial Universitario de Burgos, Burgos, Spain. 17. Endocrinology Department, Hospital Universitario Clínico San Carlos, Madrid, Spain. 18. Medical Oncology Department, Hospital Universitario Santa Lucia, Cartagena, Spain. 19. Medical Oncology Department, Hospital General Universitario de Elche, Elche, Spain. 20. Medical Oncology Department, Hospital Universitario de Canarias, Universidad de La Laguna, Tenerife, Spain. 21. Medical Oncology Department, Hospital Universitario La Fe, Valencia, Spain. 22. Pathology Department, Hospital Universitari Arnau de Vilanova, Lleida, Spain. 23. Endocrinology Department, Hospital Universitario Gregorio Marañon, Madrid, Spain. 24. Medical Oncology Department, MD Anderson Cancer Center Madrid, Madrid, Spain.
Abstract
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.
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.