Proffered paper session: NETs and endocrine tumours

Prof Chris Verslype, a digestive oncologist at UZ Leuven, shared key insights from the proffered paper session on NETs and endocrine tumours, which he chaired.

The updated CABINET trial analysis focuses on pre-treated patients with pancreatic and extrapancreatic NETs, including those treated with PRRT, everolimus, or CAPTEM. Patients were randomised to receive cabozantinib (60 mg) or placebo, with cross-over allowed upon progression. Last year’s results showed improved PFS and response rates with cabozantinib. This year’s update highlights safety concerns, with 70% of patients experiencing adverse events and 30% discontinuing treatment. Despite this, pancreatic NETs showed a robust PFS of 13.8 months and a 19% response rate, while extrapancreatic NETs had lower results, with 8.4 months PFS and a 5% response rate.

Several presentations focused on the molecular background of NETs. A new molecular classification identifies three distinct types: NS1, NS2, and NS3, with NS3 associated with poor survival. This classification is based on complex transcriptomic analyses, including methylomics. Interestingly, these molecular types appear across different primary tumour sites, such as the pancreas and small bowel, suggesting similarities despite anatomical differences. This opens up the possibility of targeting these molecular similarities with specific therapies, although much remains to be understood. Nevertheless, it provides hope for future treatment strategies.

The AXINET trial, presented at ESMO a few years ago, compared axitinib to placebo in patients with grade 1-2 extrapancreatic NETs, showing a modest gain in median survival. Due to the small benefit, axitinib was initially seen as not worth pursuing. However, translational studies revealed a three-gene signature in paraffin-embedded tissue, with one key gene coding for osteopontin. Low plasma levels of osteopontin correlated with better responses to axitinib, with patients achieving PFS of about 71 months. This highlights the importance of identifying biomarkers, like osteopontin, to select patients most likely to benefit from treatment, maximising efficacy while managing side effects of angiogenic agents in NETs.