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Changes in alpha-fetoprotein across the systemic therapy continuum in advanced hepatocellular carcinoma—a real-world, multicenter study
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Changes in alpha-fetoprotein across the systemic therapy continuum in advanced hepatocellular carcinoma—a real-world, multicenter study
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Journal Article
Changes in alpha-fetoprotein across the systemic therapy continuum in advanced hepatocellular carcinoma—a real-world, multicenter study
2024
Overview
Background:
Early changes in alpha-fetoprotein (AFP) are a promising surrogate endpoint for systemic treatment outcomes in hepatocellular carcinoma (HCC).
Objectives:
We sought to investigate the utility of AFP response across first-line sorafenib (1L SOR) and later-line checkpoint inhibitor (CPI) therapies.
Design:
We conducted a multicenter, retrospective cohort study of patients with advanced HCC who received 1L SOR and any subsequent CPI.
Methods:
The primary outcomes were overall survival (OS) and time on treatment (TOT). Pre-treatment AFP and the lowest AFP within 3 months of treatment initiation were used to calculate the percent change in AFP for each treatment. AFP response was defined as an AFP reduction by ⩾20% within 3 months, and AFP progression was defined as an increase in AFP by ⩾20% within 3 months. Patients with baseline AFP < 20 ng/mL were considered not evaluable for AFP change.
Results:
Of 176 study patients, 46 (28%) received CPI after SOR, and 125 (71%) had a baseline AFP ⩾ 20. Patients who experienced AFP response on SOR had significantly longer OS and TOT than those who did not and those who were not evaluable (OS: median 689 vs 320 vs 452 days, log-rank p < 0.001; TOT: median log of days 5.2 vs 4.5 vs 4.9, p < 0.001). Patients with AFP progression following SOR had significantly shorter OS than those who did not and those who were not evaluable (median 304 vs 557 vs 452, log-rank p = 0.008). Similarly, patients with AFP response following CPI therapy had a significantly reduced risk of death compared with those who did not have an AFP response (hazard ratio 0.13, 95% confidence interval 0.03–0.60, p = 0.009).
Conclusion:
Early AFP response with 1L SOR and any subsequent CPI was associated with longer OS and TOT, and early AFP progression was associated with shorter OS and TOT. These data support utilizing longitudinal AFP changes as a surrogate endpoint in HCC systemic therapy.
Publisher
SAGE Publications,Sage Publications Ltd,SAGE Publishing
