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.
Trial Objective & Design › | Primary Endpoints › | Secondary Endpoints › | Additional Analyses › | Key Patient & Disease Characteristics › | Treatment Characteristics & Dosimetry ›
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
Trial Objective & Design
Trial Objective
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.
Trial Design
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.
Primary Endpoints
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. |
Secondary Endpoints
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
Tumor Response4
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%.
Additional Analyses
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
Key Patient & Disease Characteristics
| TheraSphere + Chemo (N = 215) |
Chemo (N = 213) |
|
| Median Age (y) | 63.0 | 60.0 |
| Male | 135 (62.8%) | 138 (64.8%) |
| Region North America Europe Asia |
63 (29.3%) 131 (60.9%) 21 (9.8%) |
56 (26.3%) 145 (68.1%) 12 (5.6%) |
| 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%) |
| KRAS Status Mutant Wild Type |
100 (46.5%) 115 (53.5%) |
101 (47.4%) 112 (52.6%) |
| Bilobar disease | 176 (81.9%) | 173 (81.2%) |
| Liver tumor burden at baseline by BICR < 10% ≥ 10% to < 25% ≥ 25% Missing |
124 (57.7%) 54 (25.1%) 29 (13.5%) 8 (3.7%) |
121 (56.8%) 47 (22.1%) 28 (13.1%) 17 (8.0%) |
| 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%) |
Treatment Characteristics & Dosimetry
Treatment Characteristics
| TheraSphere + Chemo (N = 215) |
Chemo (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
Dosimetry
In the 185 patients treated with TheraSphere prior to progression7:
| Treatment Median Day 4 (1st Week Thursday) |
|---|
| Median Specific Activity (Single sphere): 887 Bq |
| Median dose absorbed by perfused volume: 117.0 Gy (range: 61.7-156) |
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.