The EPOCH Trial
CAUTION: Therasphere is under an investigational device exemption for treatment of patients with metastatic colorectal cancer. The safety and effectiveness for this treatment has not been established.
EPOCH is a level 1, phase III randomized controlled trial using transarterial radiation therapy for mCRC liver metastases that demonstrated statistically significant improvements in both Progression-Free Survival (PFS) and Hepatic Progression-Free Survival (hPFS) in patients who progressed on first-line chemotherapy.1
To evaluate the safety and efficacy of TheraSphere Y-90 Glass Microspheres combined with second-line therapy (oxaliplatin- or irinotecan-based chemotherapy) in patients with mCRC of the liver.
An open-label, prospective, multicenter, phase III trial of 428 patients randomized 1:1 to treatment arm (TheraSphere + second-line chemotherapy) vs. control arm (second-line chemotherapy alone) across 95 centers in 12 countries, including North America, Europe and Asia.
Progression-free survival (PFS) and hepatic PFS (hPFS)
- Time from randomization to progression or death by RECIST 1.1 or death
- Blinded independent central review (BICR)
Both primary endpoints successfully met
TheraSphere Y-90 Glass Microspheres used in combination with chemotherapy as a second-line treatment demonstrated statistically significant improvements in both PFS and hPFS in patients who progressed on first-line chemotherapy.
Progression Free Survival2
|Patients receiving TheraSphere with second-line chemo were 31% less likely to experience disease progression or death (due to any cause) vs. chemo alone.|
Hepatic Progression Free Survival3
|Patients receiving TheraSphere with second-line chemo were 41% less likely to experience hepatic disease progression or death (due to any cause) vs. chemo alone.|
Median Overall Survival (in months):
- Intent-to-Treat (ITT): 14.0 vs. 14.4 for TS+Chemo (N=215) vs. Chemo alone (N=213) (1-sided p-value: 0.7229)
- Per-Protocol (PP): 15.2 vs. 14.3 for TS+Chemo (N=115) vs. Chemo alone (N=173) (1-sided p-value: 0.3841)*
* TS+Chemo (N=100) and Chemo alone (N=40) patients excluded from Per Protocol analysis due to major deviations
Patients receiving TheraSphere Y-90 with second-line chemotherapy showed an Objective Response Rate (ORR) of 34.0% vs. 21.1% for the control arm; a difference of 12.8%.
Time to Start of Subsequent Therapy & Quality of Life
The addition of TheraSphere Y-90 to second-line chemotherapy extended the time to start of subsequent therapy without compromising quality of life.
Time to Start of Subsequent Therapy5
Time to Deterioration of Quality of Life6
|TheraSphere + Chemo
(N = 215)
(N = 213)
|Median Age (y)||63.0||60.0|
|Male||135 (62.8%)||138 (64.8%)|
|ECOG 0||119 (55.3%)||133 (62.4%)|
|Albumin ≥ Site LLN||182 (84.7%)||177 (83.1%)|
|CEA ≥ 35ng/mL||116 (54.0%)||105 (49.3%)|
|Bilobar disease||176 (81.9%)||173 (81.2%)|
|Liver tumor burden at baseline by BICR
≥ 10% to < 25%
|Maximum liver lesion size ≥ 4cm||162 (75.3%)||142 (66.7%)|
|Primary tumor in situ||83 (38.6%)||69 (32.4%)|
|Left side primary tumor location||150 (69.8%)||136 (63.8%)|
|Extrahepatic metastases at baseline||113 (52.6%)||95 (44.6%)|
|TheraSphere + Chemo
(N = 215)
(N = 213)
|Received Assigned Therapy||187 (87.0%)||191 (89.7%)|
|2nd Line Chemo Administered||203 (94.4%)||191 (89.7%)|
|Irinotecan-based / Mean Number of Cycles||130 (60.5%) / 9.0||123 (57.7%) / 9.5|
|Oxaliplatin-based / Mean Number of Cycles||73 (34.0%) / 8.5||68 (31.9%) / 8.8|
|Biological Agent||88 (40.9%)||93 (43.7%)|
|TheraSphere Y-90 Glass Microspheres Treatment|
|Median time to Y-90, days (range)||25 (12, 90)||NA|
The addition of TheraSphere Y-90 to second-line chemotherapy did not increase chemo-related adverse events and no new safety signals were identified.1
In the 185 patients treated with TheraSphere prior to progression7:
References & Footnotes
More EPOCH trial information can be found in the Journal of Clinical Oncology manuscript.
- Mulcahy, M. et al, Radioembolization With Chemotherapy for Colorectal Liver Metastases: A Randomized, Open-Label, International, Multicenter, Phase III Trial (EPOCH). Journal of Clinical Oncology, 20 Sept 2021.
- Time from randomization to progression according to RECIST 1.1 by Blinded Independent Central Review (BICR) or death (due to any cause), whichever occurred first.
- Time from randomization to hepatic progression according to RECIST 1.1 by Blinded Independent Central Review (BICR) or death (due to any cause), whichever occurred first.
- According to RECIST 1.1 by Blinded Independent Central Review (BICR).
- Time from randomization to start of the subsequent mCRC therapy (i.e. a complete change in the treatment regimen or addition of another locoregional therapy, including ablation or resection).
- Time to Deterioration of Quality of Life was a secondary endpoint and is defined as: Time from randomization to the change from baseline in FACT-c total score ≤ -7 points or death, whichever occurred first.
- Progression as assessed by investigator.