[177Lu]Lu-DOTATATE PRRT and CAPTEM chemotherapy for pancreas and small bowel neuroendocrine tumours: The AGITG CONTROL NETS Multi-centre randomized trial.

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.