A novel approach for early cancer treatment known as radioligand therapy (RLT) has been shown to significantly reduce the risk of advanced neuroendocrine tumour progression and death, according to research led by scientists at Sunnybrook Health Sciences Centre and the University of Toronto.

Results of the multi-centre clinical trial, which were published in The Lancet, provided evidence for the first time that RLT—when applied in the early stages after a patient's diagnosis—slowed down the progression of aggressive grade 2 and 3 neuroendocrine tumours of the gastrointestinal tract.

The treatment was shown to extend the average time of "progression-free survival" from approximately 8.5 months to 22.8 months.

"This is the first study to show the effectiveness of RLT as the 'first-line' treatment with advanced incurable cancer, or any cancer," said the study's global principal investigator Simron Singh, a medical oncologist at Sunnybrook and associate professor in the department of medicine at U of T's Temerty Faculty of Medicine. "This trial is groundbreaking not only for patients with neuroendocrine cancers but for all cancer patients as it has implications for the practice of cancer treatment broadly."

Singh described RLT as a "game changer" in the treatment of cancer, which has traditionally been carried out by surgery, drugs or radiation.

"While it's technically radiation, it is given via a chemotherapy route through the blood until it reaches the precise location of the tumour," said Singh, who is also an affiliate scientist at Sunnybrook Research Institute and co-founder of the Susan Leslie Clinic for Neuroendocrine Tumors at Sunnybrook's Odette Cancer Centre.

RLT involves injecting radioactive isotopes—in this case, the drug lutathera—through an IV. This method targets specific cancer cell receptors, delivering precise radiation to kill cancer cells while preserving healthy tissue.

The study evaluated the use of RLT earlier as a first-line (or "up front") treatment for patients newly diagnosed with grade 2 or 3 advanced gastrointestinal neuroendocrine tumours. Although neuroendocrine cancer is uncommon, incidence is rising rapidly, and few treatments exist for patients. This cancer is resistant to most therapies, making it challenging to treat.

The results confirm the clinical benefit of earlier use of RLT for patients diagnosed with aggressive and life-threatening tumours, said Singh. "This is the next step in personalized targeted cancer therapy for patients, focused on more effectively killing cancer cells while limiting the damage to surrounding healthy tissues."

Further investigations of RLT as a therapeutic option are ongoing to evaluate overall survival and long-term safety, which will better define the next steps for how this therapy will change cancer treatment worldwide.

The multi-site trial included investigators and participants from Canada, the United States, France, Germany, Italy, the Netherlands, South Korea, Spain and the UK. An overview of the results was presented at the 2024 American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium in January 2024.