Early Alpha-Fetoprotein Response Predicts Sustained Tumor Response Following Immune Checkpoint Inhibitors Combined with Targeted Therapy in Liver Cancer

Background: Although immune checkpoint inhibitors (ICI) have revolutionized liver cancer treatment, some patients experience early tumor progression after therapy, missing the window for other potential treatments, such as neoadjuvant therapy. Therefore, identifying the predictive factors for early progression is critical for timely therapeutic adjustment and the optimization of patient outcomes. Methods: This retrospective study enrolled patients with liver cancer who received their first ICI combined with targeted therapy at the Fifth Medical Center of the PLA General Hospital between June 2022 and December 2023. Early tumor progression was defined as tumor progression within 6 months of therapy initiation. Multivariate logistic regression analysis was used to identify independent risk factors for early tumor progression, and overall survival (OS) curves were generated using the Kaplan-Meier method. Results: A total of 159 patients were enrolled. Multivariate logistic regression analysis indicated that patients with an early alpha-fetoprotein (AFP) response had a significantly reduced risk of early tumor progression (OR = 0.34, 95% CI: 0.13-0.84, p = 0.019), suggesting that an early AFP response is a protective factor against early progression. The area under curve (AUC) for the predictive model was 0.73 (95% CI: 0.63-0.83, p < 0.001). Stratified survival analysis showed that the median overall survival (mOS) in the early AFP response group was significantly longer than that in the poor response group (17.3 months vs. 6.1 months, HR = 2.11, 95% CI: 1.19-2.74, p = 0.009). Conclusions: Early AFP response is not only an effective biomarker for identifying high-risk patients prone to early tumor progression but is also significantly associated with long-term survival in liver cancer patients treated with ICI combined with targeted therapy. This finding will enable clinicians to make timely therapeutic adjustments and optimize treatment outcomes, thereby improving both progression-free survival and overall survival.