Proffered Paper session: NETs and endocrine tumours

Prof Chris Verslype, digestive oncologist at UZ Leuven summarised two major phase III studies that significantly impact the management of GEP-NETs. 

The established efficacy of PRRT originates from the NETTER-1 trial, which demonstrated substantial benefit in patients with metastatic midgut NETs progressing after SSA therapy. PRRT significantly improved PFS compared with continued or intensified SSA therapy. At ESMO, new data were presented from XT-XTR008-3-01, a Chinese phase III study investigating ¹⁷⁷ Lu- dotatate in a broader range of tumour sites, including midgut, pancreatic and rectal NETs. This represents the first large-scale evaluation of PRRT across the full spectrum of grade 1–2 GEP-NETs.

In this study, ¹⁷⁷ Lu- dotatate was administered in four cycles every eight weeks, demonstrating consistent antitumour activity with significant PFS improvement across all subgroups. Notably, the trial enrolled patients in later lines of therapy compared with NETTER-1, making the observed efficacy particularly striking. Objective response rates exceeded 55% in pancreatic and rectal NETs—an unprecedented finding in this disease context. The treatment showed a favourable safety profile, with grade ≥3 haematologic toxicities observed in 10–15% of patients, and low incidences of MDS and renal impairment. These results confirm both the efficacy and tolerability of PRRT in non-midgut GEP-NETs, establishing its role beyond the metastatic midgut setting.

The second pivotal study, the COMPETE trial, represents another practice-changing phase III investigation. This trial compared ¹⁷⁷Lu-edotreotide PRRT with everolimus, a long-standing standard therapy in progressive GEP-NETs. Approximately 15% of patients were treatment-naïve, while the remainder had received prior SSA therapy, mirroring real-world clinical practice. PRRT with ¹⁷⁷ Lu-edotreotide was administered every 12 weeks—less frequently than in previous trials—without any apparent loss of efficacy. The study demonstrated a highly significant improvement in PFS and ORR ranging from 20% to 30%, depending on the method of assessment. Overall survival data are still immature, but safety findings were encouraging, with reduced toxicity likely attributable to the extended treatment interval.

These studies collectively confirm that PRRT is advancing toward earlier use in the treatment algorithm, particularly for grade 1 and 2 GEP-NETs.