The EPOCH Trial: Efficacy and Safety


Dr Mary Mulcahy, a key opinion leader, describes the efficacy and safety outcomes of the EPOCH clinical trial.

Mary F. Mulcahy, MD: The EPOCH trial enrolled 215 patients into the Y-90 [Yttrium-90] plus chemotherapy arm, and 213 patients into the chemotherapy alone arm. Patient characteristics were well balanced in both arms. About 60% of these cases were from European countries, 10% from Asia and 30% from the United States. All these patients were required to have an albumin of greater than 3 g/dL and a good ECOG [Eastern Cooperative Oncology Group] performance status. Of all these cases, 46% had KRAS mutations and 53% had KRAS wild type, which is comparable to what we see in the general population. Bilobar disease was present in 81% of patients enrolled in both arms. The primary tumor was left in site in about 35% of all cases. There were extrahepatic nonmetastatic lesions seen in other organs in about 50% of patients in both arms. Sixty percent of patients received irinotecan as their second line of therapy. Only about 5% of patients received an EGFR [epidermal growth factor receptor] inhibitor in addition to their second line of therapy.

There were 2 coprimary end points: progression-free survival and hepatic progression-free survival. Progression-free survival was found to favor the Yttrium-90 with chemotherapy arm, with a hazard ratio of 0.69, a confidence interval of 0.54 to 0.88, and a p-value [probability value] of less than 0.0013. This was a statistically significant benefit in progression-free survival with the addition of Yttrium-90 to systemic chemotherapy. Hepatic progression-free survival was also a primary end point. Hepatic progression-free survival also favored the Yttrium-90 with chemotherapy arm, with a hazard ratio of 0.59, confidence interval of 0.46 to 0.77, and a p-value of less than 0.0001. The hepatic progression-free survival was 7.2 months for patients in the chemotherapy alone arm and 9.1 months for patients who received Yttrium-90 in addition to systemic chemotherapy.

We identified subsets to explore prospectively during the course of this study: patients who had KRAS mutations, hepatic tumor burden of greater than 10%, fewer than 3 liver lesions, and metastatic disease arising from the left side of the colon. With the addition of a biologic agent, each of these independently had a statistically significant benefit with the addition of Yttrium-90 to chemotherapy.

Secondary end points included overall survival. There was no benefit in overall survival for the patient population enrolled in this study. Secondary end points also included response rate. An overall response rate, being either at a complete response or a partial response, was seen in 34% of cases in the Yttrium-90 arm and 21% of cases in the chemotherapy alone arm. We found that the addition of Y-90 didn’t impact the ability of patients to receive full dose systemic chemotherapy. There was no difference in either the number of cycles received or the dose intensity of chemotherapy received during the second line of therapy. In addition, there was no difference in the number of patients who were able to go on to receive third-line and subsequent chemotherapy whether or not they received Yttrium-90.

Chemotherapy-related adverse events were seen in both arms of the study. However, there was no increase in chemotherapy-related adverse events for patients who got the Yttrium-90 radioembolization in addition to chemotherapy. There was an increase in any adverse event related to the radioembolization, device, and angiogram. However, most of those weren’t serious. Approximately 10% of cases had a serious adverse event related to the device. There were an equal number of treatment-related adverse events that required discontinuation of chemotherapy: about 12% in both arms. This shows us that while the addition of the Yttrium-90 is associated with some procedure and device-related adverse events, it doesn’t impact the ability to receive adequate chemotherapy.

Transcript edited for clarity.

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