In the phase III EPOCH trial reported in the Journal of Clinical Oncology, Mary F. Mulcahy, MD, and colleagues found that the addition of transarterial yttrium-90 radioembolization (TARE) to second-line chemotherapy significantly prolonged progression-free survival and hepatic progression–free survival in patients with colorectal liver metastases.

Mary F. Mulcahy, MD

Study Details

The open-label trial included 428 patients from sites in North America, Europe, and Asia who had experienced disease progression on first-line oxaliplatin- or irinotecan-based chemotherapy. They were randomly assigned between May 2012 and August 2020 to receive second-line treatment with oxaliplatin- or irinotecan-based chemotherapy with (n = 215) or without (n = 213) TARE. TARE was given as whole-liver (separate right and left lobar injections) or unilobar treatment prior to the start of second-line chemotherapy; planned treatment was 120 Gy ± 10% using single-compartment dosimetry to either or both lobes in a single setting. The two primary endpoints were progression-free survival and hepatic progression–free survival in the intention-to-treat population on blinded independent central review.

Progression-Free Survival

Among the 215 patients in the TARE group, 187 (87%) received TARE, 16 received chemotherapy only, and 12 received no treatment. Among the 213 patients in the control group, 191 received chemotherapy and 22 received no therapy.

Median follow-up was 36.0 months (95% confidence interval [CI] = 29.6–62.2 months) in the TARE group and 42.3 months (95% CI = 30.0–47.8 months) in the control group. Median progression-free survival was 8.0 months (95% CI = 7.2–9.2 months) in the TARE group vs 7.2 months (95% CI = 5.7–7.6 months) in the control group (hazard ratio [HR] = 0.69, 95% CI = 0.54–0.88, P = .0013). Median hepatic progression–free survival was 9.1 months (95% CI = 7.8–9.7 months) in the TARE group vs 7.2 months (95% CI = 5.7–7.6 months) in the control group (HR = 0.59, 95% CI = 0.46–0.77, P < .0001).

In subgroup analyses, a significant benefit with the addition of TARE was observed for those with:

• Tumors with a KRAS mutation (HR = 0.57)
• Left-side primary tumors (HR = 0.65)
• A tumor burden of 10% to 25% (HR = 0.43)
• Three or fewer lesions (HR = 0.33)
• The addition of a received biologic agent (HR = 0.58)
• Resected primary tumors (HR = 0.63)
• No detectable extrahepatic lesions (HR = 0.68)
• Extrahepatic lesions deemed to be benign findings (HR = 0.69).

Objective response rates were 34.0% vs 21.1% (P = .0019). On ITT analysis, median overall survival was 14.0 months (95% CI = 11.8–15.5 months) vs 14.4 months (95% CI = 12.8–16.4 months; HR = 1.07, 95% CI = 0.86–1.32, P = .7229). On per-protocol analysis, median overall survival was 15.2 vs 14.3 months (HR = 0.96, 95% CI = 12.6–16.4, P = .3841). As noted by the investigators, a higher proportion of patients in the control group received subsequent therapy including TARE.

Adverse Events

Both groups received full chemotherapy dose intensity. Grade ≥ 3 adverse events occurred in 68.4% of those in the TARE group vs 49.3% of the control group; the most common in the TARE group were neutropenia (21.9% vs 13.5% of the control group) and fatigue (8.6% vs 2.9%). TARE-specific grade ≥ 3 adverse events included radiation pneumonitis (n = 1), cholecystitis (n = 2), and duodenal ulcer (n =1). No arterial dissections were reported. Grade 5 adverse events occurred in eight patients in the TARE group, consisting of radiation-induced liver disease, hepatic failure, and portal hypertension that were considered possibly related to treatment; and asthenia, intestinal obstruction, myocardial infarction, and pulmonary embolus considered unrelated to treatment. Grade 5 adverse events occurred in four patients in the control group, consisting of pulmonary embolus considered possibly related to treatment, and bowel obstruction, respiratory failure, and asthenia considered unrelated to treatment. No deaths occurred within 30 days of TARE infusion.

The investigators concluded, “The addition of TARE to systemic therapy for second-line colorectal liver metastases led to longer progression-free survival and hepatic progression–free survival. Further subset analyses are needed to better define the ideal patient population that would benefit from TARE.”

Riad Salem, MD, MBA, of the Division of Interventional Radiology, Department of Radiology, Northwestern University, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Boston Scientific Corporation. For full disclosures of the study authors, visit ascopubs.org.