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Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction
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[177Lu]Lu-DOTATATE PRRT and CAPTEM chemotherapy for pancreas and small bowel neuroendocrine tumours: The AGITG
David L Chan1, Katrin Marie Sjoquist2, David Turner Ransom3
1Royal North Shore Hospital, St Leonards, NSW, Australia; Faculty of Medicine and Health, University of Sydney, Australia.
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.
Clinical Trial Registration:
NCT02358356 / ACTRN12615000909527.
