In the trial, radioembolization (also called selective internal radiation therapy [SIRT) or sometimes transarterial radioembolization [TARE]) using glass beads (Therasphere; Boston Scientific) containing radioactive yttrium (Y-90) was used as a second-line treatment in combination with standard of care systemic chemotherapy for patients who had disease progression during or after first-line chemotherapy.
The EPOCH trialists, set their sights on determining the impact of radioembolization and second-line chemotherapy in patients with colorectal liver metastases who progressed on oxaliplatin- or irinotecan-based first-line therapy. The international, prospective phase 3 EPOCHpivotal clinical trial randomised 428 patients.
Findings from the trial, which were presented at the European Society for Medical Oncology (ESMO) Congress 2021 in the Autumn and published in theJournal of Clinical Oncology, showed that the addition of SIRT met both its primary endpoints, including progression-free survival (PFS) and hepatic progression-free survival (hPFS) of patients with metastatic colorectal cancer (mCRC) of the liver. The trial did not show significant improvement in overall survival of the patients in the SIRT arm.
The addition of TheraSphere treatment significantly increased both PFS (p=0.0013) and hPFS (p<0.0001). Patients receiving SIRT with second-line chemotherapy were 31% less likely to show disease progression or death (HR= 0.69) and 41% less likely to show hepatic disease progression or death vs. with chemotherapy alone (HR= 0.59). Median overall survival was 14 and 14.4 months (p=0.7229). There were 68.4% grade 3 adverse events reported radioembolization as compared with 49.3% in those who received chemotherapy alone. Both groups received full chemotherapy dose intensity.
Riad Salem (Northwestern Memorial Hospital, Chicago, USA) and co-principal investigator of the trial, said: “TheEPOCHtrial not only demonstrated positive safety and efficacy data for the patients treated in this study, but underscores the success of integrating a device-based therapy like TheraSphere treatment in the continuum of care with systemic chemotherapy and biologic regimens, thereby providing the rationale and setting the stage for future investigation in other cancer types.
”EPOCH is being hailed as the first positive phase 3 SIRT trial in any disease setting. The data is expected to support Boston Scientific’s regulatory submission to the US Food and Drug Administration (FDA). In the conclusion of the published article, the authors, write: “Further subset analyses are needed to better define the ideal patient population that would benefit from radioembolization.”
A previous phase 3 trial, SIRFLOX, that used a different resin yttrium-90 microsphere platform (SIR-Spheres; Sirtex/China Grand Pharmaceutical and Healthcare Holdings) failed to show significant additive benefits to chemotherapy as measured by progression-free survival at any site (but significantly delayed disease progression in the liver). The trial also did not find additive SIRT when it came to overall survival in a first-line setting. These results and subsequent analyses including a pooled analysis of SIRFLOX-FOXFIRE-FOXFIRE global, which reported some encouraging data for patients with respect to progression in the liver still did not reveal significant benefits with respect to overall survival.
Commenting on the EPOCH trial results, Mary Mulcahy, medical oncologist at Northwestern Memorial Hospital and co-principal investigator of the trial, noted: “In the second line of therapy for metastatic colorectal cancer, with disease isolated to the liver, the addition of TheraSphere with chemotherapy resulted in a significant delay in overall tumour progression. Additionally, chemotherapy-related adverse events were comparable between the trial arms.”Peter Littler (Freeman Hospital, Newcastle, UK) is the 2021 British Society of Interventional Radiology (BSIR) Scientific Programme Committee chair and has a specialist interest in interventional oncology. Speaking broadly on the availability of SIRT in the UK for this patient group, he says: “This study adds important information to existing literature in the area. SIRT availability in the UK for patients with colorectal metastases is limited to small numbers in the palliative setting in relatively few commissioned NHS (National Health Service) centres. Positive phase 3 data in this patient group should inform further evaluation of the technology, enabling greater access to SIRT for more of our patients.”