Streptozotocin plus 5-fluorouracil followed by everolimus or the reverse sequence in patients with advanced pancreatic neuroendocrine tumors (SEQTOR-GETNE phase III study): a randomized clinical trial.
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.
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-mPFS1).
Patients were randomized to everolimus (n = 72) or STZ/5-FU (n = 69) first. The 12-mPFS1 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 PFS1 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.
STZ/5-FU and everolimus were not statistically different in PFS rates, but STZ/5-FU achieved higher response rates.
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-mPFS1).
Patients were randomized to everolimus (n = 72) or STZ/5-FU (n = 69) first. The 12-mPFS1 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 PFS1 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.
STZ/5-FU and everolimus were not statistically different in PFS rates, but STZ/5-FU achieved higher response rates.
Authors
Capdevila Capdevila, Tafuto Tafuto, Krogh Krogh, Teulé Teulé, Garcia-Carbonero Garcia-Carbonero, Klümpen Klümpen, Cremer Cremer, Sevilla Sevilla, Eriksson Eriksson, Tabaksblat Tabaksblat, Metges Metges, Reed Reed, Schrader Schrader, Navarro Navarro, Valentí Valentí, Hernando Hernando, Colao Colao, Vestermark Vestermark, Carnaghi Carnaghi, Knigge Knigge, Jimenez-Fonseca Jimenez-Fonseca, Benavent Benavent, de Vos-Geelen de Vos-Geelen, Venerito Venerito, Von Werder Von Werder, Jann Jann, Rinke Rinke, Smith Smith, Hörsch Hörsch, Starling Starling, Ruszniewski Ruszniewski, Baudin Baudin, Caroli-Bosc Caroli-Bosc, Manzano Manzano, Martín Martín, Scarpa Scarpa, Lawlor Lawlor, Ragulan Ragulan, Ps Ps, Sadanandam Sadanandam, Carmona-Bayonas Carmona-Bayonas, Salazar Salazar
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