Baseline Host Biomarkers and Six-Month Sustained Drug-Free Status After Atezolizumab–Bevacizumab for Hepatocellular Carcinoma: Exploratory Clinical Stratification Using PAN-DF Score

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Abstract
Background/Objectives: Sustained drug-free status is an emerging milestone after atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma. We examined baseline host biomarkers associated with achievement of 6-month sustained drug-free status and evaluated a composite stratification score. Methods: This multicentre retrospective study included patients treated with atezolizumab plus bevacizumab. The endpoint required systemic therapy discontinuation after complete response or no viable disease, followed by at least 6 months without viable or recurrent hepatocellular carcinoma and sustained normalization of initially elevated tumour markers. The PAN-DF score (preserved hepatic reserve, altered immune-inflammatory status, and nutritional-immune reserve for achieving drug-free status) combined modified albumin–bilirubin grade, neutrophil-to-lymphocyte ratio, and prognostic nutritional index. Results: Among 655 patients, 25 achieved the endpoint; median post-discontinuation follow-up was 533 days. In the complete-case cohort (n = 473; 17 events), achievement rates were 0.0%, 2.9%, 3.7%, and 13.6% for scores 0–3. Each one-point increase was associated with higher odds of achievement (odds ratio 2.90, 95% confidence interval 1.51–5.55; p = 0.001), and the area under the curve was 0.719. The examined baseline tumour-related factors were not significantly associated with the primary endpoint, and the examined host-related factors were not associated with objective response. Conclusions: Selected baseline host biomarkers were associated with achievement of 6-month sustained drug-free status. PAN-DF stratified the observed probability of this outcome and may help identify patient groups with a relatively higher likelihood of a sustained drug-free state, supporting early multidisciplinary planning.

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