Alpha-fetoprotein as a biomarker of response to first-line chemoimmunotherapy in metastatic hepatocellular carcinoma.

Abstract

e16247 Background: Atezolizumab plus bevacizumab (Atezo/Bev) and durvalumab plus tremelimumab (Durva/Tremi) are preferred first-line regimens for patients with unresectable or metastatic hepatocellular carcinoma (HCC). Comparative real-world data to guide treatment selection remains limited. Elevated AFP is a known poor prognostic marker; however, its role as a predictive biomarker for differential treatment benefit remains understudied. Methods: We conducted a retrospective cohort study using the TriNetX database to identify adults with metastatic HCC who received first-line Atezo/Bev or Durva/Tremi after January 2022 with AFP > 1000 ng/ml. Propensity score matching was used to balance baseline demographics, liver disease characteristics, and comorbidities. Primary outcome was overall survival (OS). Secondary analyses evaluated treatment-related toxicities and outcomes in patients with high baseline AFP. Adverse events were identified using diagnosis codes and laboratory abnormalities within 3 months of treatment initiation. Results: Before matching, 712 patients treated with Atezo/Bev and 296 treated with Durva/Tremi met inclusion criteria. After propensity score matching, 269 patients per cohort were included, with well-balanced baseline characteristics. In the matched cohort, the survival probability in the atezo/bev vs durva/tremi arms was as follows- at 1 year- 50.38% vs 56.54% (p = 0.494); at 3 years-22.78% vs 27.29% (p = 0.542); at 5 years- 22.78% vs 27.29% (p = 0.542). Across sensitivity analyses the results consistently showed a trend towards improved survival with durva/tremi, though differences were not statistically significant. Toxicity profiles differed between regimens but were consistent with existing literature. Conclusions: In this real-world analysis of first-line therapy for metastatic HCC with high AFP, Durva/Tremi demonstrated a trend towards improved overall survival, albeit not statistically significant. This hypothesis-generating analysis raises the possibility that AFP may be clinically informative in decision-making for the first line of treatment. These findings need to be further verified in larger studies.