Radioligand therapy significantly prolongs progression-free survival in patients with the most common type of neuroendocrine tumours compared to standard of care

Published in The Lancet, results of the phase III COMPETE clinical trial show that the targeted radiotherapeutic agent [¹⁷⁷Lu]Lu-edotreotide significantly prolonged progression-free survival in patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEP-NETs) when compared to targeted therapy with everolimus.

Radioligand therapy works by targeting somatostatin receptors on the surface of the tumour allowing radiotherapy to be administered in a localised manner, minimising damage to surrounding healthy cells.

Led by Jaume Capdevila (VHIO), this study supports this treatment strategy as a potential new therapeutic option in early lines of therapy in patients with advanced disease.

Published in The Lancet, results of the international, open-label, superiority phase III COMPETE trial show that the radiotherapeutic [¹⁷⁷Lu]Lu-edotreotide demonstrate statistically significant and clinically meaningful benefits compared to targeted molecular therapy in patients with metastatic neuroendocrine gastroenteropancreatic tumours (GEP-NETs).

Results of this study, directed by Jaume Capdevila, Medical Oncologist at the Vall d’Hebron University Hospital and Head of the Vall d’Hebron Institute of Oncology’s (VHIO) Hepatobiliary Pancreatic Cancer and Endocrine Tumours Group, support the potential use of [¹⁷⁷Lu]Lu-edotreotide for the treatment of these patients.

Neuroendocrine Tumours (NETs) arise in neuroendocrine cells throughout the body.

While these malignant, heterogenous neoplasms are typically considered slow-growing, some are associated with rapid progression and poor prognosis.

As a result, many patients present with advanced disease at the time of diagnosis.

While NETs were historically viewed as relatively rare diseases, the incidence of these tumours has increased by more than 500% over the past three decades, underscoring an urgent, ongoing need for additional treatment options for newly diagnosed patients with advanced or inoperable tumours.

Among neuroendocrine cancers, the most prevalent originate in the gastroenteropancreatic tract (GEP-NETs), and constitute a group of complex, difficult to treat neoplasms with late diagnosis.

“Therapeutic options for patients with metastatic gastroenteropancreatic neuroendocrine tumours are limited,” said Jaume Capdevila, senior and corresponding author of the study.

“In this context, the therapeutic potential of radioligand therapy as an emerging treatment strategy is currently being evaluated in these patients. COMPETE is the first pivotal trial comparing radioligand therapy to a targeted therapy without the routine use of  concomitant somatostatin analogue therapy  in this GEP-NET patient population."

[¹⁷⁷Lu]Lu-edotreotide works by targeting somatostatin receptors that are frequently overexpressed on the surface of neuroendocrine tumour cells.

Part of the molecule specifically recognises and latches onto these tumour cell receptors and administers the radiotherapy in a localised manner, minimising damage to surrounding healthy cells.

The COMPETE trial included 309 patients with grade 1 or grade 2 inoperable, somatostatin receptor (SSTR)-positive GEP-NETS who were randomly assigned (2:1) to receive [¹⁷⁷Lu]Lu-edotreotide or targeted therapy with everolimus.

Median progression-free survival (PFS) was 23.9 months for the [¹⁷⁷Lu]Lu-edotreotide arm and 14.1 months for the everolimus arm.

“Radioligand therapy with [¹⁷⁷Lu]Lu-edotreotide demonstrated statistically significant and clinically meaningful improvements in progression-free survival, without the routine use of accompanying somatostatin analogues, which could potentially reduce side effects and limit costs. Efficacy and safety data support its potential use in early lines of therapy in patients with advanced, progressive gastroenteropancreatic neuroendocrine tumours,” concluded Jaume Capdevila.

Source: Vall d'Hebron Institute of Oncology