Australasian Gastrointestinal Trials Group (AGITG) CONTROL NET Study: 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) and capecitabine plus temozolomide (CAPTEM) for pancreas and midgut neuroendocrine tumours (pNETS, mNETS)—Final results.

Abstract

Listen

Translate article

4122 Background: CAPTEM is an accepted regimen for patients (pts) with advanced pNETs. Single agent PRRT is now a standard of care for progressive WHO Grade 1/2 mNETs. High activity was seen with PRRT/CAPTEM in a single arm Phase I/II trial. This study aims to determine the activity of combining CAPTEM with PRRT in mNETs and pNETs pts. Methods: Non-comparative randomised open label parallel group phase II trial with 2:1 randomisation to PRRT/CAPTEM (experimental arm) vs. PRRT (mNETs control) and CAPTEM (pNETS control). PRRT/CAPTEM: 7.8GBq 177Lu Octreotate (Lutate) given intravenously (IV) on day 10 every 8 weeks for 4 cycles, with concurrent oral capecitabine 750mg/m2 b.i.d. days 1-14 and temozolomide 75mg/m2 b.i.d. days 10-14 every 56 day cycle, up to 4 cycles. PRRT alone: 7.8GBq 177Lu Octreotate (Lutate) given intravenously (IV) on day 1 every 8 weeks for 4 cycles. CAPTEM alone: Oral capecitabine 750mg/m2 b.i.d. days 1-14 and days 29-42; Oral temozolomide 75mg/m2 b.i.d. days 10-14 and 38-42 every 56 day (8w) cycle. Primary endpoint: Progression free survival (PFS). mNETS: At 15 months, assuming PFS 66.4% in control arm; target PFS ³ 80%; pNETS: At 12 months, assuming PFS 60% in control arm; target PFS ³ 75%. Secondary endpoints: Objective tumor response rate (complete or partial) (OTRR), overall survival (OS), adverse events (AEs). Results: 75 pts enrolled (Dec 2015 – Nov 2018): mNETs 33 PRRT/CAPTEM, 14 PRRT, median follow up (mFU) 60.3 months; pNETS 19 PRRT/CAPTEM, 9 CAPTEM, mFU 57.5 months (mo). Late Grade 3/4 haematologic AEs: mNETS: 2/32 (6%) PRRT/CAPTEM pts and 4/13 (31%) PRRT pts. Events included myelodysplastic syndrome (40 mo), leukaemia (60 mo), pancytopenia (50 mo), anaemia (32 mo), thrombocytopenia (7 mo). No late haematologic G3/4 AEs were reported in the pNETS cohort. No late renal toxicity was identified in all study arms. Conclusions: CONTROL NETs is the first randomized trial to demonstrate efficacy for PRRT in pNETs, in addition to a standard of care. Extended follow up confirms durable CAPTEM/PRRT activity, with superior PFS in pNETs. Late haematologic toxicity was seen in both mNET PRRT arms but was not higher with additional CAPTEM. The activity of CAPTEM/PRRT in pNETs should be tested in the phase III setting. Clinical trial information: ACTRN12615000909527. [Table: see text]