Radioligand therapy delays progression in advanced GEP-NET trial
A phase 3 trial found [177Lu]Lu-edotreotide extended progression-free survival versus everolimus in metastatic gastroenteropancreatic neuroendocrine tumors.
By Tom Brennan · Health & Medicine Correspondent
3 min read
A targeted radioligand therapy delayed disease progression longer than everolimus in patients with metastatic gastroenteropancreatic neuroendocrine tumors, according to phase 3 trial results published in The Lancet. The findings matter because treatment choices remain limited for people with advanced GEP-NETs, a group of cancers often found after they have spread or become difficult to remove surgically.
The COMPETE trial tested [177Lu]Lu-edotreotide, a radiotherapeutic agent designed to deliver radiation directly to tumor cells that carry somatostatin receptors. Vall d'Hebron Institute of Oncology said the study supports the therapy as a possible option earlier in care for patients with advanced, progressive disease.
Jaume Capdevila, a medical oncologist at Vall d'Hebron University Hospital and head of VHIO's Hepatobiliary Pancreatic Cancer and Endocrine Tumors Group, directed the trial. He said patients with metastatic GEP-NETs have few therapeutic options and that radioligand therapy is being assessed as an emerging strategy for this population.
Trial compared radiotherapy with targeted therapy
COMPETE was an international, open-label, randomized superiority trial. It enrolled 309 patients with grade 1 or grade 2 inoperable, somatostatin receptor-positive GEP-NETs, according to the study report.
Participants were assigned in a 2:1 ratio to receive either [177Lu]Lu-edotreotide or everolimus, a targeted molecular therapy. The trial compared outcomes without routine accompanying somatostatin analog therapy, according to Vall d'Hebron Institute of Oncology.
Median progression-free survival was 23.9 months among patients given [177Lu]Lu-edotreotide, compared with 14.1 months among those treated with everolimus, the investigators reported. Progression-free survival measures the length of time patients live without their cancer worsening.
Capdevila said the improvement was statistically significant and clinically meaningful. He also said use without routine somatostatin analogs could potentially reduce side effects and costs, and that the efficacy and safety data support possible use in earlier treatment lines for advanced, progressive GEP-NETs.
How the drug targets tumor cells
Radioligand therapy uses a molecule that binds to a target on cancer cells and carries a radioactive payload. In the case of [177Lu]Lu-edotreotide, the target is the somatostatin receptor, which is frequently overexpressed on neuroendocrine tumor cells, according to Vall d'Hebron Institute of Oncology.
By attaching to those receptors, the treatment delivers radiation locally to the tumor. The aim is to limit exposure to nearby healthy tissue while attacking cancer cells.
Neuroendocrine tumors begin in neuroendocrine cells found throughout the body. Vall d'Hebron Institute of Oncology said these cancers are often described as slow-growing, but some progress quickly and carry a poor prognosis.
Gastroenteropancreatic neuroendocrine tumors are the most common neuroendocrine cancers, according to the institute. They arise in the gastrointestinal tract and pancreas and are described as complex cancers that are frequently diagnosed late.
The institute said the recorded incidence of neuroendocrine tumors has risen by more than 500% over the past three decades. The COMPETE investigators said that trend adds to the need for more treatment options for patients whose tumors are newly diagnosed, advanced or inoperable.
The study, titled “[177Lu]Lu-edotreotide versus everolimus for gastroenteropancreatic neuroendocrine tumours (COMPETE),” was authored by Thomas Walter and colleagues and published in The Lancet.
This story draws on original reporting from Medical Xpress.