Transarterial Yttrium-90 Radioembolization Plus Second-Line Chemo Yield Longer PFS In Colorectal Liver Metastases


Patients with colorectal liver metastases who were treated with transarterial Yttrium-90 radioembolization plus second-line chemotherapy experienced a long-term survival benefit.

Treatment with transarterial Yttrium-90 radioembolization (TARE) and second-line chemotherapy resulted in an improved progression-free survival (PFS) and hepatic PFS (hPFS) in patients, according to data from the phase 3 EPOCH study (NCT01483027) published in the Journal of Clinical Oncology.

Treatment with TARE and chemotherapy resulted in a median PFS of 8.0 months (95% CI, 7.2-9.2) and compared with 7.2 months (95% CI. 5.7-7.6) in the control group (HR, 0.69; 95% CI, 0.54-0.88: 1-sided P = .0013). Additionally, a median hPFS of 9.1 months (95% CI, 7.8-9.7) was reported in the TARE group vs 7.2 months (95% CI, 5.7-7.6) in the chemotherapy alone group (HR, 0.59; 95% CI, 0.46-0.77; 1-sided P <.0001).

“In EPOCH, the primary end points of PFS and hPFS were longer with the addition of TARE to second-line chemotherapy. Moreover, delayed progression was observed for tumors with KRAS mutation, left-side primary tumor, hepatic tumor burden of 10% to 25%, less than 3 lesions, addition of a biologic agent, and resected primary,” the investigators wrote.

A total of 428 patients were randomly assigned 1:1 to receive either the chemotherapy plus TARE (n = 215) or chemotherapy alone (n = 213). In the TARE arm, 187 (87%) patients received TARE, 16 patients received chemotherapy only, and 12 did not receive treatment. Among those in the control arm, 191 received second-line chemotherapy and 22 received no therapy. From random assignment, the median time to TARE was 25 days. Additionally, the median overall follow-up time from the TARE group was 36.0 months (95% CI, 29.6-62.2) vs 42.3 months (95% CI, 30.0-47.8) in the control arm.

Additional findings from the trial indicated that the overall survival (OS) in the TARE group was 14.0 months (95% CI, 11.8-15.5) and 14.4 months in the control group (95% CI, 12.8-16.4; 1-sided P = .7229; HR, 1.07; 95% CI, 0.86-1.32).

The overall response rate in the TARE group was 34.0% (95% CI, 28.0%-40.5%) vs 21.1% in the control group (95% CI, 16.2%-27.1%; nominally superior 1-sided P = .0019). Moreover, the disease control rate in the TARE group was 79.5% (95% CI, 73.6%-84.4%) compared with 72.8% (95% CI, 66.4%-78.3%; 1-sided P =.0626) in the control group. The per-protocol median OS in the TARE group and control groups were 15.2 months (95% CI, 12.7-17.7) and 14.3 months (95% CI, 12.6-16.4; 1-sided P =.3841; HR, 0.96; 95% CI, 0.74-1.24), respectively.

Patients with KRAS mutations experienced a PFS benefit with TARE plus chemotherapy (HR, 0.57; 95% CI, 0.40-0.80), as well as those with a left-sided primary tumor (HR, 0.65; 95% CI, 0.48-0.88), a tumor burden of 10% to 25% (HR, 0.43; 95% CI, 0.26-0.75), 3 or fewer lesions (HR, 0.33; 95% CI, 0.14-0.76). Benefit was also observed in those who received an additional biologic agent (HR, 0.58; 95% CI, 0.40-0.84) and a primary resection (HR, 0.63; 95% CI, 0.46-0.85). Additionally, the PFS benefit of TARE extended to those with no detectable extrahepatic lesions (HR, 0.68; 95% CI, 0.47-0.96), and those with benign extrahepatic lesions (HR, 0.69; 95% CI, 0.49-0.98).

In terms of safety, 68.4% of patients in the TARE cohort experienced grade 3 adverse effects (AEs) compared with 49.3% in the control group. Several grade 3 or higher AEs related to treatment with TARE occurred, the most common being radiation pneumonitis (n = 1), cholecystitis (n = 2), and duodenal ulcer (n = 1). Investigations reported that no arterial dissections occurred in this group. A total of 12 grade 5 AEs occurred, including 8 patients from the TARE group who developed radiation-induced liver disease, hepatic failure, and portal hypertension, as well as 4 patients in the chemotherapy group experienced bowel obstruction, respiratory failure, and asthenia. Within 30 days of TARE infusion, investigators reported that no deaths occurred.


Mulcahy MF, Mahvash A, Pracht M, et al. Radioembolization with chemotherapy for colorectal liver metastases: a randomized, open-label, international, multicenter, phase III trial. J Clin Oncol. Published Online September 20, 2021. doi:10.1200/JCO.21.01839

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