Patients with high-grade gastroenteropancreatic neuroendocrine tumours showed significantly improved progression-free survival (PFS) and objective response rates after treatment with [177Lu]Lu-DOTA-TATE, according to a Phase III clinical trial presented at the ASCO Gastrointestinal Cancers Symposium, which took place in San Francisco, California, USA. Most tumours of this type are advanced at the time of diagnosis, with authors estimating that 20–30% are Grade II–III. ASCO expert Cathy Eng stated this therapy could fill the critical gap in evidence-based care that currently exists for patients affected by these tumours. The trial is the first Phase III trial for this patient population, and the first trial of first-line radioligand therapy for a metastatic solid tumour.
In total, 226 patients (median age: 61 years; 53.5% male) with newly diagnosed somatostatin receptor-positive high Grade II or III advanced gastroenteropancreatic neuroendocrine tumours were randomised 2:1 to receive either four cycles of [177Lu]Lu-DOTA-TATE plus 30 mg octreotide long-acting release at 8-weekly intervals (treatment arm), or 60 mg of octreotide long-acting release every 4 weeks (control arm). Of these patients, 35% had Grade III tumours, 29.2% had tumours in the small intestine, and 54.4% had tumours in the pancreas. The primary endpoint was PFS, and the secondary endpoint was objective response rate.
Results showed significantly extended PFS in the treatment arm (22.8 months), compared to the control arm (8.5 months). Furthermore, overall response rate was significantly higher in the treatment arm (43.0%), versus the control arm (9.3%). Researchers further noted a 72.4% reduction in the risk of disease progression in patients on the treatment arm. Some adverse events were reported, including anaemia, Grade III–IV leukopenia, and thrombocytopaenia, each seen in fewer than three patients, as well as myelodysplastic syndrome in one patient.
Lead author Simron Singh, Odette Cancer Centre at Sunnybrook Health Sciences Centre, Toronto, Canada, stated: “Our study showed significant PFS and unprecedented response rates, offering a new, safe treatment option in a field with no established standard of care.” Future research will collect additional safety and overall survival data over a longer follow-up of 3 years.
