Conventional transarterial chemoembolization combined with systemic therapy versus systemic therapy alone as second-line treatment for unresectable colorectal liver metastases: randomized clinical trial

BACKGROUND: The combination of conventional transarterial chemoembolization (cTACE) and systemic therapy has the potential to treat chemotherapy-refractory unresectable colorectal liver metastases (CRLMs). This study aimed to compare survival after this combined treatment versus systemic chemotherapy alone. METHODS: This single-centre RCT included patients with unresectable CRLMs that progressed after first-line treatment. Patients were randomized on a 1 : 1 basis to either systemic chemotherapy with or without cTACE, without further stratification. The primary outcome was progression-free survival (PFS). Secondary outcomes were overall response rate, disease control rate, conversion rate to liver resection, overall survival, and adverse events. RESULTS: Of 180 patients recruited, 168 were randomized. Eighty-five patients in arm A received systemic chemotherapy plus cTACE and 83 in arm B received systemic chemotherapy alone. Median PFS was longer in arm A than B (6.7 versus 3.8 months; hazard ratio (HR) 0.67, 95 per cent c.i. 0.49 to 0.91; P = 0.009), but did not translate into prolonged median overall survival (18.4 versus 14.8 months; HR = 0.92, 0.62 to 1.36; P = 0.669). Overall response rates (20 versus 22 per cent; P = 0.788) and conversion rate to liver resection (18 versus 16 per cent; P = 0.730) were no different between arms A and B. The disease control rate was higher in arm A than arm B (67 versus 51 per cent; P = 0.030). No adverse event higher than grade 3 according to the Common Terminology Criteria for Adverse Events was observed during treatment. CONCLUSION: Systemic chemotherapy plus cTACE is a safe option as second-line treatment for unresectable colorectal liver metastases, with a modest effect on PFS. Registration number: NCT03783559 (http://www.clinicaltrials.gov).