Baseline TGF-β May Predict Response, PFS, OS for HCC Patients Receiving Pembrolizumab

By Jeff Craven /alert Contributor
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The plasma concentration of transforming growth factor beta (TGF-β) at baseline may help predict response, progression-free survival, and overall survival in patients with hepatocellular carcinoma (HCC) treated with pembrolizumab as second-line therapy, according to recent research presented at the ASCO 2019 Annual Meeting.

Lynn G. Feun, MD, professor and co-leader of Melanoma Site Disease Group, Sylvester Comprehensive Cancer Center at the University of Miami in Miami, FL, said that they performed the study to identify which patients with unresectable HCC responded to receiving pembrolizumab (PEM).

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“Not all HCC patients respond to pembrolizumab, and PD-1 expression is not consistently helpful, so we were looking for plasma biomarkers to help,” Feun told MD /alert.

In the study, 29 patients who did not respond to or refused treatment with sorafenib received 200 mg of intravenous PEM every 3 weeks. The researchers looked at biomarkers TGF-β, PD-1, PD-L1, PD-L2 and interleukin (IL) cytokines IL-1β, IL-6, IL-8, IL-10, IL-12, IL-18 in addition to CXCL9, CCL4, CCL5, and IFN-γ.

Overall, there was a complete response in 1 patient, a partial response in 8 patients and stable disease in 4 patients. Baseline TGF-β was the sole biomarker that predicted response among patients, and the mean plasma TGF-β in patients who responded to PEM was 141.9 pg/ml compared with 1,071.8 pg/ml for patients who did not respond. The researchers determined plasma concentration of TGF-β of ≥ 200pg/ml was an index cut-off for non-responders (P = .003). Patients with TGF-β < 200 pg/ml had an overall survival (OS) and progression-free survival (PFS) of greater than 25 months compared with the 7-month OS (P = .005) and 2-month PFS (P = .008) for patients with TGF-β ≥ 200pg/ml.

“Since tumor PD-L1 expression is upregulated by IFN-γ, and IL-10, and interacts with PD-1 to suppress T cell, to confirm these relationships, the linear regression was used to analyze the data,” the researchers wrote in their abstract.

The researchers noted that there was a positive correlation between PD-1 and PD-L1 levels and plasma IFN-γ or IL-10 levels (P < .05). PD-L1 scoring was available for tumors in 9 of 24 patients, and patients with PD-L1-positive tumors also had high plasma IFN-γ or IL-10 levels (P < .05).

Feun LG, et al. Abstract e14043. ASCO 2019 Annual Meeting; May 31-June 4; Chicago, IL.