KEY TAKEAWAYS
- A post-hoc analyses of the EPOCH Phase 3 trial that evaluated the potential benefit of adding TARE with yttrium-90 glass microspheres to second-line chemotherapy (chemo) versus chemo alone in patients with liver-dominant mCRC.
- The trial’s randomization was stratified by key prognostic factors, including KRAS status, but not ECOG status and baseline CEA levels.
- Researchers investigated the impact of prognostic factors on primary and secondary endpoints, including PFS, hPFS, OS, and TTDQOL, in two subgroups of patients with different prognostic factors.
- The study’s findings suggest that TARE plus chemo may be a promising treatment approach for liver-dominant mCRC patients who meet certain prognostic criteria, and that future trials should consider stratifying randomization based on additional prognostic factors beyond KRAS status.
Patients with liver-dominant metastatic colorectal cancer were the primary focus of the original EPOCH trial, which aimed to compare the effectiveness of second-line chemotherapy (chemo) with and without transarterial radioembolization (TARE) using yttrium-90 glass microspheres (mCRC). Stratification at the time of randomization was performed according to crucial prognostic markers such KRAS status, although ECOG status and baseline CEA levels were not taken into account. In order to improve patient selection, we report post-hoc studies exploring the effect of prognostic variables on primary and secondary outcomes.
The EPOCH study was a Phase 3 randomised, open-label, multinational, parallel-group investigation. Progression-free survival (PFS) and hepatic PFS were the primary measures of efficacy (hPFS). Secondary outcomes included overall survival (OS) and time to decline in quality of life (TTDQOL). Subgroup A (excluding patients with ECOG=1 and CEA35ng/mL) and Subgroup B (excluding patients with KRAS wild-type and either ECOG=0 or CEA35ng/mL) were analysed separately in post-hoc analysis. The effectiveness of TARE in combination with chemotherapy was compared to that of chemotherapy alone using Kaplan-Meier analyses, hazard ratios (HRs), and log-rank testing.
Subgroup A saw a total of 160 patients (75.1%) assigned to the chemotherapy-only arm, while Subgroup B had 143 (66.5%) assigned to the TARE arm. Subgroup B saw 91 patients (42.7% of the total) assigned to the chemotherapy-only arm and 77 patients (35.8% of the total) assigned to the TARE arm. In this article, they present results for the intent-to-treat group for progression-free survival, hazard-adjusted progression-free survival, overall survival, and treatment-related quality of life.
There was no difference in OS between the TARE plus chemo arm and the chemo only arm, but PFS, hPFS, and TTDQOL were all significantly better for the TARE plus chemo arm compared to the chemo only arm in both subgroups A and B. To determine which patients may reap the most benefits from TARE in combination with second-line chemotherapy, careful patient selection using numerous prognostic criteria is required. The degree of improvement exhibited in patients treated with TARE and chemo as opposed to chemo alone was significantly affected by prognostic variables.
Source:https://meetings.asco.org/abstracts-presentations/215975
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT01483027/
Harris, W.P. and Salem, R. (2023). The EPOCH trial: Identifying key patient subgroups to optimize treatment planning. Journal of Clinical Oncology, 41(4_suppl), pp.130–130. doi:https://doi.org/10.1200/jco.2023.41.4_suppl.130.
