The EPOCH Trial title with TheraSphere vial on blue background.

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.

EPIC Trial Design graphic showing eligibility criteria, stratification, treatment and follow-up assessment.
*TARE with Y-90 glass microspheres (TheraSphere™, Boston Scientific Corporation). Cycle 1= chemotherapy, Y-90 TARE replace Cycle 2, Cycle 3 resume chemotherapy ± targeted therapy. ClinicalTrials.gov Identifier: NCT01483027. Chauhan N, Mulcahy MF, Salem R, et al. JMIR Res Protoc. 2019;8(1):e11545. doi: 10.2196/11545.

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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

31 percent image Patients receiving TheraSphere with second-line chemo were 31% less likely to experience disease progression or death (due to any cause) vs. chemo alone.
Progression free survival chart.

 

Hepatic Progression Free Survival3

41 percent image 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.
Hepatic Progression Free Survival chart.

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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%.

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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 start of subsequent therapy chart.

Time to Deterioration of Quality of Life6

time to deterioration of quality of life chart.

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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%)

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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:

 

dosimetry approach pie chart.
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)
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References & Footnotes

More EPOCH trial information can be found in the Journal of Clinical Oncology manuscript.

  1. 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. 
  2. 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. 
  3. 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. 
  4. According to RECIST 1.1 by Blinded Independent Central Review (BICR).  
  5. 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). 
  6. 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.  
  7. Progression as assessed by investigator.
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.
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