J. Capdevila, Salvatore Tafuto, Merete Krogh, Àlex Teulé, Rocio García‐Carbonero, Heinz‐Josef Klümpen, Birgit Cremer, Isabel Sevilla, Bengt O. Eriksson, Elizaveta Mitkina Tabaksblat, J-P. Metges, Nicholas Reed, J. Schrader, V. Navarro, Vicente Valentí, J. Hernando, Annamaria Colao, L. Vestermark, Carlo Carnaghi, Ulrich Knigge, Paula Jiménez‐Fonseca, Marta Benavent, Judith de Vos‐Geelen, Marino Venerito, Alexander von Werder, Henning Jann, Anja Rinke, Denis Smith, Dieter Hörsch, Naureen Starling, P. Ruszniewski, Eric Baudin, François‐Xavier Caroli‐Bosc, José Luís Manzano, María Ángeles Martín, Aldo Scarpa, Rita T. Lawlor, Chanthirika Ragulan, H. Ps, Anguraj Sadanandam, Alberto Carmona‐Bayonas, Ramón Salazar
Background Everolimus or streptozotocin plus 5-fluorouracil (STZ/5-FU) are approved treatments for patients with pancreatic neuroendocrine tumors (panNETs). The SEQTOR trial aimed to assess the optimal treatment sequence. Patients and methods SEQTOR was an international, open-label, randomized, crossover, phase III trial that recruited adults with unresectable or metastatic, advanced, well-differentiated panNET. Patients received 10 mg/day of everolimus followed upon progression by STZ/5-FU; or the reverse sequence. The primary endpoint was the 35-month progression-free survival (PFS) rate after first- and second-line treatment; however, due to slow accrual and longer survival, it was changed to the 12-month PFS rate following first-line treatment (12-mPFS 1 ). Results Patients were randomized to everolimus ( n = 72) or STZ/5-FU ( n = 69) first. The 12-mPFS 1 was 71.4% [95% confidence interval (CI) 59.4% to 81.6%] and 61.8% (95% CI 49.2% to 73.3%) (odds ratio 0.65, 95% CI 0.32-1.32) with a median PFS 1 of 19.4 versus 22.7 months for everolimus and STZ/5-FU, respectively. STZ/5-FU achieved a significantly higher overall response rate in first-line (11.6% versus 30.3%, P = 0.012) and second-line (30.6% versus 9.1%, P = 0.072) treatments. No differences were shown in overall survival (median 61.7 versus 50.6 months in everolimus first and STZ/5-FU first, respectively; hazard ratio 1.43, 95% CI 0.86-2.37). Discontinuations of everolimus were more frequent. Conclusion STZ/5-FU and everolimus were not statistically different in PFS rates, but STZ/5-FU achieved higher response rates.