Novel framework for response evaluation criteria in grade 1/2 neuroendocrine tumors (RECIN) following [177Lu]Lu-DOTATATE therapy: post-hoc analysis of the phase 2 LuCAP trial.

Objective: Treatment response assessment in grade 1/2 neuroendocrine tumors (NETs) has been a key challenge due to their indolent nature. Here, we propose the novel response evaluation criteria with [68Ga]Ga-somatostatin analogue (SSA)-PET/CT in grade 1/2 NETs (RECIN) following [177Lu]Lu-DOTATATE therapy and evaluate its survival impact vis-à-vis conventional radiographic response assessment. Methods: This was a post-hoc analysis of the phase 2 LuCAP trial, wherein somatostatin receptor-positive, advanced grade 1/2 gastroenteropancreatic NET patients were treated with [177Lu]Lu-DOTATATE ± capecitabine. Tumor response assessment was done with serial [68Ga]Ga-DOTANOC-PET/CECT. Up to five target lesions were evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for radiographic response. Summed SULpeak of maximum five hottest lesions were evaluated for molecular response. Associations with progression-free survival (PFS) were evaluated using hazard ratios (HRs) and their 95% confidence intervals (95%CIs) along with Harrell's C-index. Results: Seventy-two patients were included with 23/72 (32%) patients achieving RECIST-partial response (PR). The novel RECIN-PR was defined as ≥ 25% decrease in summed SULpeak or conventional RECIST-PR with no signs of radiographic progression. Based on this, 40/72 (56%) patients achieved RECIN-PR. In particular, of the 42 patients with RECIST-stable disease, 17 (40%) had RECIN-PR. RECIN-PR was associated with significantly better PFS (HR: 0.33, 95%CI: 0.15-0.76; C-index: 0.67) and had better predictive ability compared to RECIST-PR (HR: 0.52, 95%CI: 0.21-1.29; C-index: 0.60). Conclusions: In advanced grade 1/2 NETs treated with [177Lu]Lu-DOTATATE, [68Ga]Ga-SSA-PET/CT-based novel RECIN framework proved superior to conventional radiographic response assessment in terms of early response detection in indolent disease and better predictive ability.

Background: Clinical Trials Registry-India, CTRI/2020/01/022636.