Highlights from the phase III EPOCH trial

The EPOCH trial is the first phase III international study evaluating the use of Yttrium 90 radioembolization and chemotherapy for the treatment of patients with colorectal liver metastases.

The liver is unique in that it receives two separate blood supplies. The hepatic artery brings oxygenated blood from the heart to the liver, while the portal vein carries blood containing the digested nutrients and toxins from the gastrointestinal tract to the liver for processing before reaching the body’s systemic circulation. Most normal liver cells are primarily fed by the portal vein (supplies 70-75% of the liver’s blood supply), while tumour cells in the liver are almost exclusively fed or vascularized by the hepatic artery (supplies the remaining 25-30% of the liver’s blood supply). By blocking part of the hepatic artery blood flow helps to destroy cancer cells, leaving most of the healthy liver cells unharmed as they will continue to receive their blood supply from the portal vein.

Embolization is a procedure that injects substances directly into an artery in the liver with the goal of blocking blood supply to cancer cells. Radioembolization or SIRT (selective internal radiation therapy) combines embolization and radiation therapy to treat liver cancer, delivering a localized, high dose of radiation to the tumour cells while sparing normal tissue. It can help patients shrink tumours that cannot be removed by surgery, improving their quality of life. Microscopic beads known as microspheres (32 microns in diameter, which is small enough to pass freely through the hepatic artery, but too large to pass through the capillaries of the tumour where they get lodged and can deliver their localized radiation) which contain a radioactive isotope (yttrium-90, or Y-90 for short) attached to them are infused into the hepatic artery. The radiation can spread about 2,5mm around the sphere, which really helps to keep the radiation localized. A radioactive isotope is a species or variation of a particular chemical element that is unstable and spontaneously emits radiation. Once the radioactive microspheres are infused into the hepatic artery, they release small amounts of radiation to the tumour site over several days. The radiation travels a very short distance, which enables the radiation to be highly localized and have a minimal impact on surrounding healthy tissues.

The following video illustrates how the Y-90 microspheres work:

https://www.youtube.com/watch?v=YndyQkSZl5I&ab_channel=SirtexMedicalUS

The EPOCH trial is the first phase III international study evaluating safety and efficacy of Y-90 radioembolization and chemotherapy for the treatment of patients with colorectal liver metastases who did not respond to first-line chemotherapy.

The study

Patients with colorectal cancer (CRC) liver metastases were randomly assigned to receive either:

• Y-90 radioembolization and standard of care chemotherapy with or without targeted therapy, or

• Standard of care chemotherapy with or without targeted therapy

Adding Y-90 radioembolization to chemotherapy resulted in statistically significant increases to progression free survival and hepatic progression free survival, whereas no significant differences were found in overall survival. Overall response rate in the radioembolization-chemotherapy group was significantly better than in the standard of care arm. Chemotherapy related adverse events were similar between the two groups, and there were no new unexpected safety concerns associate with the experimental treatment. Furthermore, the experimental treatment resulted in promising responses among patients with KRAS-mutated CRC, for which limited treatment options are currently available. As such, further exploration of this treatment within this patient group is warranted.

Take away message:

The addition of radioembolization to standard of care chemotherapy resulted in statistically significant improvements to progression free survival and hepatic progression free survival among patients with colorectal cancer liver metastases that did not respond to first-line chemotherapy.