[177Lu]Lu-DOTATATE PRRT and CAPTEM chemotherapy for pancreas and small bowel neuroendocrine tumours: The AGITG CONTROL NETS Multi-centre randomized trial
Mené sur 72 patients atteints d'un cancer du pancréas ou d'une tumeur neuroendrocrine de l'intestin grêle, cet essai randomisé de phase II évalue l'efficacité, du point de vue de la survie sans progression, d'une chimiothérapie de type CAPTEM (capécitabine et témozolomide) en combinaison avec le [177Lu]Lu-DOTATATE (Lutétium-177-dotatate)
Background/Aim: To evaluate the efficacy of [177Lu]Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) plus capecitabine and temozolomide (CAPTEM) in participants(pts) with progressive WHO Grade 1-2 neuroendocrine tumours: pancreas(pNETs) and small bowel(SBNETs).
Methods: Non-comparative randomized open label parallel group phase II trial, 2:1 randomization to PRRT/CAPTEM (experimental arm) vs PRRT (SBNETs control) and CAPTEM (pNETs control). PRRT/CAPTEM: 7.8 GBq [177Lu]Lu-DOTATATE i.v. Day 10, 8 weekly x 4, concurrent CAP 750 mg/m2 b.i.d. Days 1-14 and TEM 75 mg/m2 b.i.d. Days 10-14. CAPTEM Q 4 weekly (pNET control arm). Primary endpoint: Progression-free survival (PFS) @ 15 months (SBNETS) (target > 80%), and 12 months (pNETs) (target >75%). Other: Objective response rate (ORR), overall survival and adverse events (AE). Extended follow-up was undertaken after initial analysis.
Results: Seventy-two patients were enrolled and evaluable (27 pNETs, 45 SBNETs). The pNET 12 month PFS was 83.3% (PRRT/CAPTEM) and 88.9% (CAPTEM), and 27 month PFS was 61.1% (PRRT/CAPTEM) and 33.3% (CAPTEM). The SBNET 15 month PFS was 90.4% (PRRT/CAPTEM) and 92.3% (PRRT), and 36 month PFS was 60.4% (PRRT/CAPTEM) and 61.5% (PRRT). PFS HR was HR 0.41 (95% CI: 0.15- 1.12, p = 0.08) for pNETs and 1.17 (95% CI: 0.51-2.68, p = 0.71) for SBNETs. ORR for pNETs was 72.2% (PRRT/CAPTEM) and 33.3% for CAPTEM, and for SBNETs 34% (PRRT/CAPTEM) and 23% for PRRT. PRRT treatment-related myeloid neoplasms were noted in 2/63 participants (3%).
Conclusions: AGITG CONTROL NETs is the first randomized trial to demonstrate efficacy for PRRT/CAPTEM in pNETs. Extended follow-up confirms durable activity, with higher PFS and ORR in pNETs. The efficacy of CAPTEM/PRRT in pNETs should be tested in a phase III trial.
European Journal of Cancer , résumé, 2026