In the international phase III EPOCH trial, patients with colorectal liver metastases who experienced disease progression on first-line therapy derived significant benefit from treatment with transarterial yttrium Y-90 radioembolization in combination with systemic chemotherapy, according to Mary F. Mulcahy, MD, of Northwestern University, Chicago.1 The study findings were simultaneously published in the Journal of Clinical Oncology.2
![Mary F. Mulcahy, MD](/media/14018067/28-mulcahy.jpg)
Mary F. Mulcahy, MD
“EPOCH is the first positive phase III global study of transarterial Y-90 radioembolization and chemotherapy in the second-line treatment of patients with colorectal liver metastases. The addition of transarterial Y-90 radioembolization to second-line systemic therapy for colorectal liver metastases resulted in significantly longer progression-free survival and hepatic progression-free survival,” Dr. Mulcahy reported. “This is the first arterial radiotherapy device to demonstrate a statistically significant delay in progression of metastatic colorectal cancer.”
Transarterial radioembolization with Y-90 glass microspheres provides selective internal radiotherapy, with beta-emitting particles delivered through the hepatic vasculature into tumor-feeding arteries. The inherent vascularity of hepatic colorectal lesions in the arterial phase provides a strong rationale for the investigation of glass-based transarterial radioembolization in the second-line setting, she explained.
Transarterial radioembolization with Y-90 plus chemotherapy resulted in a median progression-free survival of 8.0 months, vs 7.2 months with chemotherapy alone (hazard ratio [HR] = 0.69; P = .0013). Hepatic progression-free survival was increased as well to 9.1 months, vs 7.2 months (HR = 0.59; P < .0001). However, no significant differences were seen in overall survival.
About EPOCH
The EPOCHtrial enrolled 428 patients with unresectable unilobar or bilobar liver metastases who were fit for chemotherapy (irinotecan- or oxaliplatin-based), with or without targeted therapy, as second-line treatment. The liver tumor burden was less than 10% in more than half the patients, and more than two-thirds of patients had a maximum lesion size of at least 40 mm. Approximately two-thirds had at least 6 lesions, and more than one-third had at least 10 lesions. About half the study patients had nonmetastatic extrahepatic lesions at baseline. Almost half the patients had KRAS mutations.
Patients were randomly assigned 1:1 to receive chemotherapy alone or chemotherapy plus transarterial radioembolization with Y-90 glass microspheres. For that arm, patients received chemotherapy in cycle 1, transarterial radioembolization with Y-90 in cycle 2 (replacing chemotherapy, for one cycle), and chemotherapy with or without targeted therapy in cycle 3. They were followed every 8 weeks until disease or hepatic disease progression.
Second-line therapy was irinotecan-based in 60%; biologics were part of treatment for 42%; bevacizumab was given to 42%, and less than 5% received an agent targeting epidermal growth factor receptor.
Co-primary endpoints were progression-free survival and hepatic progression-free survival by blinded independent central review. Statistical significance was set at a one-sided alpha level of 0.00248.
Primary Endpoints Met
The study met its two primary endpoints, significantly improving progression-free and hepatic progression-free survival (Table 1).
In key subgroups, the transarterial radioembolization/chemotherapy approach yielded considerable improvement in progression-free survival in patients with KRAS mutations (HR = 0.57), left-sided primaries (HR = 0.65), hepatic tumor burden of between10% and 25% (HR = 0.43), and fewer than three lesions (HR = 0.33), as well as in patients receiving a biologic as part of second-line treatment (HR = 0.58). Outcomes for hepatic progression-free survival mirrored these findings.
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Median overall survival was 14.0 months in the combination arm and 14.4 months in the chemotherapy arm (HR = 1.07; P = .7229). Approximately one-third of patients in each arm were alive at 18 months.
Overall response rates were 34.0% with transarterial radioembolization/chemotherapy and 21.1% with chemotherapy alone. Stable disease was observed in 45.6% and 51.6%, respectively. Approximately 13% of patients in both arms had progressive disease as best response.
Safety Profile
According to Dr. Mulcahy, Y-90 did not compromise the ability to receive additional chemotherapy, and chemotherapy-related adverse events were similar between the groups. Treatment-emergent adverse events requiring discontinuation of chemotherapy were similar between the arms, occurring in about 12% of patients.
However, 55% of those given transarterial radioembolization had an adverse event related to the device, and 29% had an angiographic procedure–related adverse event. Serious treatment-emergent adverse device events were observed in 20 patients (10.7%) in the transarterial radioembolization group, and 8 of them (4.3% overall) had a fatal outcome.
DISCLOSURE: Dr. Mulcahy has received institutional research funding from Boston Scientific.
REFERENCES
1. Mulcahy MJ, Salem R, Mahvash A, et al: Radioembolization with chemotherapy for colorectal liver metastases: A randomized, open-label, international, multicenter, phase III trial (EPOCH study). ESMO Congress 2021. Abstract LBA21. Presented September 20, 2021.