Adding Thymosin Alpha-1 to Liver Cancer Immunotherapy Extended Survival by 5 Months | Research

The takeaway

Patients with inoperable liver cancer who received thymosin alpha-1 alongside standard immunotherapy survived a median of 16 months versus 11 months without the peptide, with no increase in side effects.

16 vs 11 months survival
Adding thymosin alpha-1 to standard immunotherapy provided a 5-month median survival advantage in unresectable liver cancer

What the researchers found

Adding thymosin alpha-1 (a peptide that boosts immune function) to a combination of lenvatinib (a targeted therapy) and sintilimab (a checkpoint inhibitor) significantly improved outcomes in unresectable liver cancer. Patients receiving the triple combination lived a median of 16 months compared to 11 months without thymosin alpha-1 — a 5-month survival advantage (p=0.018).

Progression-free survival nearly doubled: 7 months vs. 4 months (p=0.006). The tumor response rate was also higher at 55.8% vs. 34.7% (p=0.042). Crucially, adding thymosin alpha-1 did not increase side effects — adverse event rates were similar between groups.

Why it matters

Unresectable liver cancer has limited treatment options and poor prognosis. This study suggests thymosin alpha-1 may enhance the effectiveness of modern cancer immunotherapy by strengthening the immune system's ability to attack tumors — without adding toxicity. If confirmed in larger trials, this peptide could become a standard addition to liver cancer treatment regimens.

The numbers in context

n=92 (43 experimental, 49 control) · median OS 16 vs 11 months (p=0.018) · median PFS 7 vs 4 months (p=0.006) · ORR 55.8% vs 34.7% (p=0.042) · DCR 76.7% vs 59.2% (p=0.073) · no difference in adverse events

How the study worked

Retrospective study of 92 patients with unresectable hepatocellular carcinoma treated at a single Chinese hospital from January 2020 to June 2022. Patients were divided into two groups based on treatment: thymosin alpha-1 plus lenvatinib and sintilimab (n=43) versus lenvatinib and sintilimab alone (n=49). Tumor responses were evaluated using mRECIST criteria. Adverse events were graded using CTCAE version 5.0.

Who was studied

Patients with unresectable hepatocellular carcinoma at a Chinese hospital

What this study cannot tell us

This is a retrospective, single-center study without randomization. Treatment group assignment was based on physician choice, introducing potential selection bias. The sample size of 92 patients limits statistical power. Being conducted at one Chinese hospital, results may not generalize to other populations. A prospective randomized trial would provide stronger evidence.

How to read the evidence

This is moderate-evidence from a retrospective observational study. The significant survival difference and consistent results across multiple endpoints are promising, but the lack of randomization and single-center design limit the strength of causal conclusions.

When this study was published

Published in 2025 using data from 2020-2022, this is very current research reflecting the latest era of cancer immunotherapy combinations.

The bigger picture

Thymosin alpha-1 has been used for decades in parts of Asia to boost immune function in hepatitis and cancer patients. As modern immunotherapy (checkpoint inhibitors) becomes the backbone of cancer treatment, there's growing interest in combining it with immune-boosting peptides. This study adds to the evidence that thymosin alpha-1 may enhance checkpoint inhibitor effectiveness — a concept being explored across multiple cancer types.

Questions still open

Would a prospective randomized trial confirm the survival benefit of adding thymosin alpha-1 to this regimen?
What is the mechanism by which thymosin alpha-1 enhances checkpoint inhibitor therapy in liver cancer?
Could thymosin alpha-1 similarly improve outcomes when added to immunotherapy for other cancer types?

Common questions

What is thymosin alpha-1 and how does it work in cancer treatment?

Thymosin alpha-1 is a peptide naturally produced by the thymus gland that helps mature and activate T cells — the immune cells that can recognize and kill cancer. By boosting T cell function, it may enhance the effectiveness of checkpoint inhibitor drugs like sintilimab, which work by removing the 'brakes' that prevent immune cells from attacking tumors.

Is thymosin alpha-1 available as a cancer treatment?

Thymosin alpha-1 (sold as Zadaxin) is approved in some countries, particularly in Asia, for hepatitis B and as an immune booster. It is not FDA-approved in the United States for any indication. Its use in cancer treatment, as described in this study, is still being investigated and would be considered off-label or experimental in many countries.

Read the original research

The efficacy and safety of thymosin alpha-1 combined with lenvatinib plus sintilimab in unresectable hepatocellular carcinoma: a retrospective study.

Scientific reports, 15(1), 13960

View on PubMed ↗Publisher’s paper ↗

Citation

Yao, Siyang; Huang, Qiangsong; Zou, Yan; Liu, Tianqi; Yang, Yongyu; Huang, Tao; Zhao, Yuanquan; Dong, Xiaofeng. (2025). The efficacy and safety of thymosin alpha-1 combined with lenvatinib plus sintilimab in unresectable hepatocellular carcinoma: a retrospective study.. Scientific reports, 15(1), 13960. https://doi.org/10.1038/s41598-025-97160-7