Abstract

BackgroundColorectal cancer is one of the most common cancers and causes of cancer-related death. Up to approximately 70% of patients with metastatic colorectal cancer (mCRC) have metastases to the liver at initial diagnosis. Second-line systemic treatment in mCRC can prolong survival after development of disease progression during or after first-line treatment and in those who are intolerant to first-line treatment.ObjectiveThe objective of this study is to evaluate the efficacy and safety of transarterial radioembolization (TARE) with TheraSphere yttrium-90 (90Y) glass microspheres combined with second-line therapy in patients with mCRC of the liver who had disease progression during or after first-line chemotherapy.MethodsEPOCH is an open-label, prospective, multicenter, randomized, phase 3 trial being conducted at up to 100 sites in the United States, Canada, Europe, and Asia. Eligible patients have mCRC of the liver and disease progression after first-line chemotherapy with either an oxaliplatin-based or irinotecan-based regimen and are eligible for second-line chemotherapy with the alternate regimen. Patients were randomized 1:1 to the TARE group (chemotherapy with TARE in place of the second chemotherapy infusion and subsequent resumption of chemotherapy) or the control group (chemotherapy alone). The addition of targeted agents is permitted. The primary end points are progression-free survival and hepatic progression-free survival. The study objective will be considered achieved if at least one primary end point is statistically significant. Secondary end points are overall survival, time to symptomatic progression defined as Eastern Cooperative Oncology Group Performance Status score of 2 or higher, objective response rate, disease control rate, quality-of-life assessment by the Functional Assessment of Cancer Therapy-Colorectal Cancer questionnaire, and adverse events. The study is an adaptive trial, comprising a group sequential design with 2 interim analyses with a planned maximum of 420 patients. The study is designed to detect a 2.5-month increase in median progression-free survival, from 6 months in the control group to 8.5 months in the TARE group (hazard ratio [HR] 0.71), and a 3.5-month increase in median hepatic progression-free survival time, from 6.5 months in the control group to 10 months in the TARE group (HR 0.65). On the basis of simulations, the power to detect the target difference in either progression-free survival or hepatic progression-free survival is >90%, and the power to detect the target difference in each end point alone is >80%.ResultsPatient enrollment ended in October 2018. The first interim analysis in June 2018 resulted in continuation of the study without any changes.ConclusionsThe EPOCH study may contribute toward the establishment of the role of combination therapy with TARE and oxaliplatin- or irinotecan-based chemotherapy in the second-line treatment of mCRC of the liver.Trial RegistrationClinicalTrials.gov NCT01483027; https://clinicaltrials.gov/ct2/show/NCT01483027 (Archived by WebCite at http://www.webcitation.org/734A6PAYW)International Registered Report Identifier (IRRID)RR1-10.2196/11545

Highlights

  • Colorectal cancer is the third most common newly diagnosed cancer and the fourth most common cause of cancer death globally [1]

  • The EPOCH study may contribute toward the establishment of the role of combination therapy with transarterial radioembolization (TARE) and oxaliplatin- or irinotecan-based chemotherapy in the second-line treatment of metastatic colorectal cancer (mCRC) of the liver

  • The prognosis for metastatic colorectal cancer remains poor, with a 5-year survival rate around 14% [5]; the 5-year relative survival is worse for patients with metachronous metastasis than for those with synchronous metastasis (17.6% vs 7.2%) [6]

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Summary

Introduction

Colorectal cancer is the third most common newly diagnosed cancer and the fourth most common cause of cancer death globally [1]. Metastatic disease is observed at first diagnosis in an estimated 25% of new patients (synchronous distant metastasis) [2] and eventually develops in a further estimated 60% of patients (metachronous metastasis) [2,3,4]. The prognosis for metastatic colorectal cancer (mCRC) remains poor, with a 5-year survival rate around 14% [5]; the 5-year relative survival is worse for patients with metachronous metastasis than for those with synchronous metastasis (17.6% vs 7.2%) [6]. Up to approximately 70% of metastatic patients present with mCRC to the liver at the initial diagnosis [7]. Up to approximately 70% of patients with metastatic colorectal cancer (mCRC) have metastases to the liver at initial diagnosis. Second-line systemic treatment in mCRC can prolong survival after development of disease progression during or after first-line treatment and in those who are intolerant to first-line treatment

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