Dr Mary Mulcahy explains the rationale and study design of the phase III EPOCH clinical trial.
Mary F. Mulcahy, MD: The majority of metastatic colorectal cancer is metastatic disease to the liver. The addition of liver-directed therapies can theoretically enhance somebody’s progression-free survival and hopefully overall survival. Many liver-directed therapies have been evaluated, and it’s been shown that surgery or ablation can enhance somebody’s cure rate. However, 80% of cases aren’t amenable to surgical resection or local ablation. For those cases, we pursued Yttrium-90 TheraSphere as an option for controlling liver disease while also delivering systemic chemotherapy.
This study was designed as a second-line study, and second line was chosen because we wanted to give patients time to have their first line of therapy demonstrate that they truly have liver-only disease, and then enroll in second-line treatment with systemic chemotherapy and the addition of Yttrium-90 TheraSphere. Patients who had unresectable unilobar or bilobar colorectal liver metastases were enrolled. They were able to receive either irinotecan or oxaliplatin as their second line of therapy. They had measurable disease by RECIST [Response Evaluation Criteria in Solid Tumors], a good performance status, a bilirubin of less than 1.2 times the upper limit of normal, and an albumin of greater than or equal to 3 g/dL.
These patients were stratified by whether they had unilobar or bilobar disease, their KRAS mutation status being wild type or mutant, and whether they received oxaliplatin or irinotecan as their first line of therapy. They were then randomized 1:1 to either systemic chemotherapy alone, which was combination chemotherapy with an appropriate biologic agent as available—whatever the standard of care was at the institution—or the same systemic chemotherapy with the addition of Yttrium-90 TheraSphere in place of their second cycle. Patients received whole liver treatment in place of their second cycle of systemic chemotherapy.
We chose to design it this way so that all patients could start their second line of chemotherapy at comparable times, and it allows for time to do the planning studies that are needed to deliver Yttrium-90 TheraSphere. Patients continued on systemic chemotherapy and were evaluated for response assessment every 8 weeks. The end point that we were seeking was either progression anywhere in the body or progression within the liver. Both of those—progression-free survival and hepatic progression-free survival—are independent primary end points for this study.
Transcript edited for clarity.