Transarterial Radioembolization Slows Progression of CRC With Liver Mets

Transarterial yttrium-90 radioembolization (TARE) combined with second-line chemotherapy improved progression-free survival (PFS) in patients with unresectable colorectal cancer liver metastases, according to results from the randomized phase III EPOCH trial.

With the addition of TARE, median PFS increased from 7.2 to 8.0 months (HR 0.69, 95% CI 0.54-0.88, 1-sided P=0.0013) and hepatic PFS increased from 7.2 to 9.1 months (HR 0.59, 95% CI 0.46-0.77, 1-sided P<0.0001), reported Mary Mulcahy, MD, of Northwestern University’s Feinberg School of Medicine in Chicago, during a session of the virtual European Society for Medical Oncology meeting.

The study was simultaneously published in the Journal of Clinical Oncology.

The 12-month PFS rates were 25.8% in the TARE-chemotherapy arm and 13.2% in the chemotherapy-alone arm, while the 12-month hepatic PFS rates were 29.8% and 13.5%, respectively.

While the liver is the most common site for metastases from colorectal cancer, about 80% of these patients are ineligible for resection, Mulcahy said. “Non-surgical approaches for liver-confined, inoperable colorectal metastases may offer clinically meaningful benefit beyond that of systemic therapy alone.”

“This is the first positive phase III trial with TARE that prolonged progression-free survival and hepatic progression-free survival,” said discussant Thomas Gruenberger, MD, of Health Network Vienna in Austria. “The important message is that the best patients are the ones with liver-limited disease unresponsive to first-line treatment.”

The overall response rate with added TARE was 34% compared with 21.1% for chemotherapy alone.

However, there was no overall survival (OS) benefit with the combination, with a median OS of 14 months with TARE and 14.4 months with chemotherapy alone (HR 1.07, 95% CI 0.86-1.32), the authors noted.

Additionally, there were eight treatment-emergent adverse events (TEAEs) leading to death in the TARE arm, and four in the chemotherapy-alone arm.

In an accompanying editorial, Robert Lentz, MD, and Wells Messersmith, MD, both of the University of Colorado Cancer Center in Aurora, wrote that the study “provides minimal support” for adding TARE to second-line chemotherapy for unresectable colorectal cancer liver metastases.

“[S]mall improvements in PFS are unlikely to justify lack of improved OS, increased toxicity (including TARE-related deaths), and substantial cost,” they pointed out.

In this international multicenter trial, 428 patients from 95 centers in North America, Europe, and Asia were randomized 1:1 to receive second-line chemotherapy with or without TARE.

Median overall follow-up times were 36.0 months in the TARE arm and 42.3 months in the chemotherapy-alone arm.

An analysis of treatment effects by patient subgroups demonstrated a benefit in PFS with TARE for:

• Tumors with KRAS mutation (HR 0.57, 95% CI 0.40-0.80)
• Hepatic tumor burden of 10% to 25% (HR 0.43, 95% CI 0.26-0.72)
• Three or fewer lesions (HR 0.33, 95% CI 0.14-0.76)
• Left-sided primary tumor (HR 0.65, 95% CI 0.48-0.88)
• The addition of a biologic agent (HR 0.58, 95% CI 0.40-0.84)
• Resected primary tumor (HR 0.63, 95% CI 0.46-0.85)

The PFS benefit with added TARE was shown for those with no detectable extrahepatic lesions (HR 0.68, 95% CI 0.47-0.96), as well as those with extrahepatic lesions deemed to be benign (HR 0.69, 95% CI 0.49-0.98)

As for safety, grade 3 or higher TEAEs were more frequent in the TARE arm (68.4% vs 49.3% with chemo alone), as were serious TEAEs (37.4% vs 20.8%, respectively).

Chemotherapy-related TEAEs were similar between the two arms (92.0% and 91.3%, respectively), as were the TEAEs requiring discontinuation of chemotherapy (12.8% vs 12.1%).

“We have to keep in mind that there were more severe side effects in the TARE group, including deaths,” Gruenberger noted. “And what is important in such a trial is quality of life, which has not been reported so far.”

“Therapies for metastatic colorectal cancer patients should accomplish at least one of two goals: to improve quality of life and to extend survival. In all these trials, TARE was unable to accomplish either one,” Lentz and Messersmith wrote. “The standard of care for unresectable colorectal liver metastases remains systemic therapy without the addition of liver-directed therapy.”