Early tumor marker decrease to predict the efficacy of combination therapy with lenvatinib plus anti-PD-1 antibodies in unresectable hepatocellular carcinoma (uHCC).

Abstract

304 Background: Combination therapy with anti-angiogenic agents plus anti-PD-1 antibodies has shown high anti-tumor activity in uHCC. However, predicting the efficacy of this combination therapy remains a challenge. Methods: This study included consecutive patients with uHCC who received lenvatinib (8 mg/d regardless of body weight) and an anti-PD-1 antibody as first-line systemic therapy between Sep 2018 and July 2020, and had at least one imaging evaluation. Tumor response was assessed every 2 months (± 2 week) by the investigators using modified RECIST criteria. Patients were evaluated as having a radiological response (complete or partial response) or non-radiological response (stable disease or progressive disease) at the best overall response evaluation. Serum tumor markers for HCC, including alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), were evaluated at baseline and 2-3 weeks after therapy was initiated and their association with radiological response were assessed. Patients with baseline AFP or PIVKA-II between the upper limit of normal and the maximum measuring range of the kit were evaluable for AFP decrease or PIVKA-II decrease. Results: A total of 76 patients were eligible for this study. Baseline AFP ≥400 ng/mL or PIVKA-II ≥400 mAU/mL was not associated with radiological response (P = 0.167 and P = 0.916, respectively). At 2-3 weeks after the initiation of therapy, 51 patients were evaluable for AFP decrease; 78.4% experienced a > 20% AFP decrease and 51.0% experienced a > 50% AFP decrease. Patients with a > 50% AFP decrease had a higher rate of radiological response than those with AFP increase or a ≤50% AFP decrease (73.1% vs 32.0%, P = 0.003). In 57 patients evaluable for PIVKA-II decrease, 50.9% and 35.1% experienced a > 20% and > 50% PIVKA-II decrease, respectively. Patients with a > 50% PIVKA-II decrease had a higher rate of radiological response than those with PIVKA-II increase or a ≤50% PIVKA-II decrease (85.0% vs 29.7%, P < 0.001). Both AFP decrease > 50% and PIVKA-II decrease > 50% predicted radiological response, with an area under receiver operating characteristic curve of 0.706 (95% CI, 0.560-0.852, P = 0.012) and 0.752 (95% CI, 0.621-0.883, P = 0.001), respectively. Furthermore, patients with a > 20% AFP or PIVKA-II increase from baseline had a lower rate of radiological response (0% vs 57.4%, P = 0.043; and 21.7% vs 69.7%, P < 0.001, respectively). Conclusions: A tumor marker decrease was seen in most patients as early as 2-3 weeks after the initiation of the combination therapy. Early on-treatment AFP or PIVKA-II decrease may serve as a predictor for objective response for patients with uHCC receiving combination anti-angiogenic and immune therapy.