New research on patients with intermediate hepatocellular carcinoma (HCC) who have undergone conventional transarterial chemoembolization (cTACE) suggests that the duration of a response to a treatment, rather than the robustness of the response, may be a better predictor of overall survival. The study was published in JAMA Network Open.1

This novel surrogate end point, dubbed sustained response duration (SRD), was defined as the time between when a complete response (CR), partial response (PR), or stable disease is first observed and the date progressive disease occurs after cTACE.

Although a radiological CR is generally believed to be a good measure of treatment efficacy, the investigators explained that following cTACE in HCC, relapse can still happen. The theory about why this may occur is based on the belief that lingering viable tumor cells that appear to be dead are actually just in a state of shock and, as a result, the cells can prompt disease recurrence.

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To test the utility of SRD as a surrogate for OS, the investigators conducted a retrospective study on prospectively collected data from 2 medical centers in China. The first arm enrolled 2403 treatment-naive patients with HCC who underwent cTACE between June 1, 2000, and December 31, 2008. The second validation cohort enrolled 331 treatment-naive patients from January 1, 2011, to June 30, 2012. All patients (2734 in total) were between ages 18 and 75; had Child-Pugh scores of A5, A6, or B7; and had Eastern Cooperative Oncology Group performance scores of 0. Patients who had missing radiological images were excluded.

Across all patient response durations after cTACE, SRD of 6 months or longer was strongly associated with 5-year OS, with a median OS in this group of 67.7 months. The median OS in those who had SRD of less than 6 months was 53.5 months. Patients with SRD of 6 months or more had better OS than initial responders (hazard ratio [HR], 1.723; 95% confidence interval [CI], 1.620-1.832; P < .001) and best responders (HR, 1.870; 95% CI, 1.775-1.971; P < .001).

In a subgroup analysis, patients with a SRD of 6 months or more had better OS than initial responders (HR, 1.969; 95% CI, 1.172-2.264; P < .001) regardless of tumor size, the presence of a tumor capsule, or the number of tumors present in each patient. Risk of death for patients with a SRD of 6 months or longer was found to be 85%, whereas it was 60% and 30% for initial responders and best responders, respectively.

Objective response based on radiological images may not be an appropriate surrogate end point for this patient population, the authors reasoned, as tumor biology and elements of the tumor microenvironment have the potential to alter the efficacy of cTACE, subsequently impacting patient survival.