Early alpha-fetoprotein response predicts prognosis of immune checkpoint inhibitor and targeted therapy for hepatocellular carcinoma: a systematic review with meta-analysis

ABSTRACT

Background

The prognostic value of alpha-fetoprotein (AFP) response for efficacy of targeted therapy or immune checkpoint inhibitors (ICIs) has not been established. The purpose of this meta-analysis is to elucidate the relationship between AFP response and survival outcomes in hepatocellular carcinoma (HCC) patients who received targeted therapy or ICIs.

Methods

The hazard ratio (HR) with 95% confidence interval (CI) was used to evaluate the relationship between AFP response and overall survival (OS)/progression-free survival (PFS).

Results

Twenty-six articles containing 3056 HCC patients were finally included in the study. The pooled results showed that after targeted therapy or ICIs, patients with decrease in AFP had better prognosis (OS:HR = 0.48, 95%CI:0.40–0.56; PFS:HR = 0.39, 95%CI:0.33–0.46), while patients with increase in AFP had worse prognosis (OS:HR = 2.30, 95%CI:1.82–2.89; PFS:HR = 2.34, 95%CI = 1.69–3.24). Subgroup analysis revealed that compared to AFP decrease >50%, AFP decrease >20% can better predict the prognosis of patients who received targeted therapy (OS:HR = 0.51, 95%CI:0.41–0.62; PFS:HR = 0.39, 95%CI:0.30–0.51) or ICIs treatment (OS:HR = 0.34, 95%CI:0.16–0.71; PFS:HR = 0.22, 95%CI:0.10–0.47), and 8 weeks after targeted therapy may be the appropriate time point for AFP assessment.

Conclusion

AFP decrease >20% within 8 weeks may be the appropriate definition for early AFP response which probably works best in predicting the efficacy of therapy.

Registration

The review was not registered.

KEYWORDS:

• alpha-fetoprotein
• hepatocellular carcinoma
• targeted therapy
• immune checkpoint inhibitor
• meta-analysis

Abbreviations:

HCC, hepatocellular carcinoma; AFP, Alpha-fetoprotein; ICIs, immune checkpoint inhibitors; PD-L1, programmed cell death ligand-1; OS, overall survival; PFS, progression-free survival; QUIPS, Quality in Prognosis Studies; HR, hazard ratio; CI, confidential interval.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/17474124.2022.2156859

Additional information

Funding

This work was supported by the grants from the Taishan Scholars Program of Shandong Province, National Natural Science Foundation of China (Grant No. 82073200 & 81874178), Major Basic Research of Shandong Provincial Natural Science Foundation (Grant No. ZR2021ZD26), and Funds for Independent Cultivation of Innovative Team from Universities in Jinan (Grant No. 2020GXRC023).