Circulating tumor DNA (ctDNA) is a promising, emerging biomarker to monitor treatment responses and disease progression in patients with hepatocellular carcinoma (HCC), according to results presented at the virtual 2020 ASCO Annual Meeting.

“ctDNA has emerged as a promising biomarker for noninvasive monitoring of treatment response and disease progression in many tumor types. However, the clinical use of ctDNA in patients with HCC has not been established,” Chih-Hung Hsu, MD, National Taiwan University Cancer Center, Taipei City, and colleagues wrote.

This led Dr Hsu et al to evaluate longitudinal and personalized detection of ctDNA for monitoring treatment response to atezolizumab plus bevacizumab in patients with unresectable HCC not previously treated with systemic therapy.

Overall, 48 patients from a subset of patients enrolled in Arm A of the GO30140 trial were included in the study. All patients received treatment with atezolizumab in combination with bevacizumab.

Serial plasma samples were collected at baseline, during treatment (cycle 2, day 1 and cycle 4, day 1), and at disease progression.

Whole exome sequencing was performed on archival tumor tissues or fresh biopsies prior to treatment to identify somatic mutations specific to each patient’s tumor mutational signatures in individual tumors.

Of the 48 patients enrolled in the trial, personalized ctDNA assays (Signatera) were successfully designed for 47 patients.

At baseline, a median of 25.7 ng of cell-free DNA was extracted from 2-mL plasma samples. ctDNA was detected in 45 (96%) of 47 patients with a median of 70.6 mean tumor molecules/mL of plasma and a median of 1.8% mean variant allele frequency in plasma.

Dr Hsu and colleagues noted that higher ctDNA levels at baseline appeared to be associated with increased tumor burden (P <.03) and dynamic changes in ctDNA levels after treatment were associated with response at cycle 4, day 1.

Positive ctDNA status at baseline changed to negative in 7 (70%) of 10 patients achieving complete response, 3 (27%) of 11 patients achieving a partial response, and 1 (9%) of 11 patients with stable disease.

Additionally, longer PFS was reported in patients with undetectable ctDNA after treatment. Median PFS in patients with ctDNA at cycle 4, day 1, was 6.5 months and was not reached in those without ctDNA at cycle 4, day 1 (HR, 12 [1.7-93]; log-rank P <.00029).

“Our study showed that Signatera, a personalized and tumor-informed ctDNA assay, could be used as a sensitive method for detecting ctDNA in patients with unresectable HCC,” Dr Hsu and colleagues wrote.

“More importantly, our results illustrate the promise of ctDNA as an emerging biomarker that may potentially help to monitor treatment responses and disease progression in patients with HCC,” they added.—Janelle Bradley

Hsu C, Lu S, Abbas A, et al. Longitudinal and personalized detection of circulating tumor DNA (ctDNA) for monitoring efficacy of atezolizumab plus bevacizumab in patients with unresectable hepatocellular carcinoma (HCC). Presented at: the 2020 ASCO Annual Meeting; May 29-31, 2020. Abstract 3531.