The EPOCH Trial.

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 Trial Design and Primary Endpoints

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 13 countries, including North America, Europe and Asia.

EPIC Trial Design graphic showing eligibility criteria, stratification, treatment and follow-up assessment
1. 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.

 

Primary Endpoints

Progression-free survival (PFS) and hepatic PFS (hPFS)

  • Time from randomization to progression or death by RECIST 1.1.
  • Blinded independent central review (BICR)

 

Primary Endpoints Met

TheraSphere transarterial radiation therapy used as a second-line treatment option, demonstrated statistically significant improvements in both primary endpoints of PFS and hPFS in patients with colorectal liver metastases.

 

Primary Endpoints of Progression-Free Survival and Hepatic Progression-Free Survival

1. TARE with Y-90 glass microspheres (TheraSphere™, Boston Scientific Corporation). Cycle 1= chemotherapy, Y-90 TARE replaces 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.

 

Progression Free Survival

According to RECIST 1.1 by Blinded Independent Central Review

Hepatic Progression Free Survival chart out to 54 months.
Hepatic Progression Free Survival Primary Endpoints.

 

Hepatic Progression Free Survival

According to RECIST 1.1 by Blinded Independent Central Review

Hepatic Progression Free Survival chart out to 54 months.
Hepatic Progression Free Survival Primary Endpoints.

 

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 with major protocol deviations which may affect their efficacy evaluation were excluded

Tumor Response

Patients receiving TheraSphere with second-line chemotherapy showed an ORR of 34.0% vs. 21.1% (1-sided p-value: 0.0019) of the control arm which yielded a difference of 12.8%

 

Overall Response Rate*

According to RECIST 1.1 by Blinded Independent Central Review | ITT Population

best overall response rate chart.

 

Dosimetry Approach

In the 187 patients who received TheraSphere: 108 procedures were 1st week vials, 41 procedures were 2nd week vials and 38 procedures were a combination of 1st and 2nd week vials.

Treatment Median
Day 4 (1st Week Thursday)
Median Specific Activity
(Single sphere): 887 Bq
1st week Vials: 65%
2nd week Vials: 35%
In 185 patients receiving TheraSphere before Progression, median dose absorbed by perfused volume was 117.0 Gy (61.7-156)

 

Patient & Disease Characteristics

  Y-90 + 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
  < 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

  Y-90 + 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%)
Y-90 Treatment    
Median absorbed dose to perfused volume, Gy (range) 117 (61.7, 156) NA
Median time to Y-90, days (range) 25 (12, 90) NA

 

 

Secondary efficacy endpoints also include quality of life assessment by FACT-C questionnaire, time to symptomatic progression and adverse events.

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.

Reference: Journal of Clinical Oncology manuscript

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