Optimal patient selection for yttrium-90 glass plus chemotherapy in the treatment of colorectal liver metastases: additional quality of life, efficacy, and safety analyses from the EPOCH study.

ABSTRACT

BACKGROUND: Evaluating transarterial radioembolization (TARE) in patients with metastatic colorectal carcinoma of the liver who have progressed on first-line chemotherapy (EPOCH) demonstrated superior outcomes using yttrium-90 glass microspheres plus chemotherapy (TARE/Chemo) vs chemotherapy (Chemo) to treat colorectal liver metastases. Additional exploratory analyses were undertaken to assess the impact of TARE/Chemo on efficacy, safety, time to subsequent therapy, time to deterioration in quality of life (QoL), and identify criteria for improved patient selection. METHODS: Time to deterioration in QoL was analyzed for the primary study population. Subsequently, a post hoc analysis was undertaken to identify subgroups for which time to deterioration in QoL was improved with TARE/Chemo vs Chemo. Progression-free survival (PFS), hepatic (h)PFS, time to subsequent therapy, and safety outcomes were compared between treatments. RESULTS: The primary population showed no significant difference in time to deterioration in QoL between treatment arms; however, significance was seen in 2 identified subgroups, namely Subgroup A (N = 303) which excluded patients with both Eastern Cooperative Oncology Group (ECOG) 1 and baseline CEA ≥ 35 ng/mL from both treatment arms; subgroup B (N = 168) additionally excluded patients with KRAS (Kirsten rat sarcoma) mutation. In subgroup A, TARE/Chemo patients (N = 143) demonstrated superior outcomes vs Chemo (N = 160) PFS (9.4 vs. 7.6 months, hazard ratio (HR) 0.64; 1-sided P = .0020), hPFS (10.8 vs. 7.6 months, HR 0.53; 1-sided P < .0001), time to deterioration in QoL (5.7 vs. 3.9 months, HR 0.65; 1-sided P = .0063), and time to subsequent therapy (21.2 vs. 10.5 months, HR 0.52; 1-sided P < .0001). Subgroup B patients showed similar but larger significant differences between treatment arms. Median PFS, hPFS, and time to deterioration in QoL were numerically greater for TARE/Chemo in both subgroups vs the primary population, with the greatest magnitude of difference in subgroup B. Both subgroups exhibited higher percentage of CEA responders and improved ORR with TARE/Chemo vs chemo alone. Safety (reported as event rate/100 patient-years) was higher with Chemo in all populations. Additional efficacy analyses in the primary population are also reported. CONCLUSIONS: Careful patient selection, including consideration of the prognostic factors ECOG, baseline CEA, and KRAS status, sets outcome expectations in patients with colorectal liver metastases suitable for TARE/Chemo as second-line treatment (Trial Registry Number NCT01483027).