Spahn Stephan, Roessler Daniel, Pompilia Radu, Gabernet Gisela, Gladstone Beryl Primrose, Horger Marius, Biskup Saskia, Feldhahn Magdalena, Nahnsen Sven, Hilke Franz J, Scheiner Bernhard, Dufour Jean-François, De Toni Enrico N, Pinter Matthias, Malek Nisar P, Bitzer Michael
Department Internal Medicine I, Eberhard-Karls University, 72076 Tuebingen, Germany.
Department of Medicine II, University Hospital Ludwig-Maximilians-University (LMU), 81377 Munich, Germany.
Cancers (Basel). 2020 Dec 18;12(12):3830. doi: 10.3390/cancers12123830.
Immune checkpoint inhibitors (ICIs) belong to the therapeutic armamentarium in advanced hepatocellular carcinoma (HCC). However, only a minority of patients benefit from immunotherapy. Therefore, we aimed to identify indicators of therapy response. This multicenter analysis included 99 HCC patients. Progression-free (PFS) and overall survival (OS) were studied by Kaplan-Meier analyses for clinical parameters using weighted log-rank testing. Next-generation sequencing (NGS) was performed in a subset of 15 patients. The objective response (OR) rate was 19% median OS (mOS)16.7 months. Forty-one percent reached a PFS > 6 months; these patients had a significantly longer mOS (32.0 vs. 8.5 months). Child-Pugh (CP) A and B patients showed a mOS of 22.1 and 12.1 months, respectively. Ten of thirty CP-B patients reached PFS > 6 months, including 3 patients with an OR. Tumor mutational burden (TMB) could not predict responders. Of note, antibiotic treatment within 30 days around ICI initiation was associated with significantly shorter mOS (8.5 vs. 17.4 months). Taken together, this study shows favorable outcomes for OS with low AFP, OR, and PFS > 6 months. No specific genetic pattern, including TMB, could identify responders. Antibiotics around treatment initiation were associated with worse outcome, suggesting an influence of the host microbiome on therapy success.
免疫检查点抑制剂（ICIs）属于晚期肝细胞癌（HCC）的治疗手段。然而，只有少数患者能从免疫治疗中获益。因此，我们旨在确定治疗反应的指标。这项多中心分析纳入了99例HCC患者。采用加权对数秩检验，通过Kaplan-Meier分析研究临床参数的无进展生存期（PFS）和总生存期（OS）。对15例患者的亚组进行了二代测序（NGS）。客观缓解（OR）率为19%，中位总生存期（mOS）为16.7个月。41%的患者PFS>6个月；这些患者的mOS显著更长（32.0个月对8.5个月）。Child-Pugh（CP）A和B级患者的mOS分别为22.1个月和12.1个月。30例CP-B级患者中有10例PFS>6个月，其中3例有客观缓解。肿瘤突变负荷（TMB）无法预测反应者。值得注意的是，在ICI开始前30天内使用抗生素治疗与显著更短的mOS相关（8.5个月对17.个月）。综上所述，本研究表明低甲胎蛋白、客观缓解和PFS>6个月的患者总生存期预后良好。没有特定的基因模式（包括TMB）能够识别反应者。治疗开始前后使用抗生素与更差的预后相关，提示宿主微生物群对治疗效果有影响。
