Juarez-Vignon Whaley Juan J, Osataphan Soravis, Ponvilawan Ben, Charoenngam Nipith, Peters Mary Linton
Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA.
Harvard Medical School, Boston, MA.
JCO Precis Oncol. 2025 May;9:e2400475. doi: 10.1200/PO-24-00475. Epub 2025 May 29.
PD-L1 positivity in biliary tract cancers (BTCs) is reported from 4% to 76%. BTC clinical trials have not demonstrated PD-L1 expression as a predictor of response to chemotherapy combined with immune checkpoint inhibitor (chemo-ICI). This meta-analysis examines PD-L1 positivity rates in BTC and association between PD-L1 expression and outcomes in patients treated with chemo-ICI.
Observational studies or clinical trials reporting tissue-based PD-L1 expression by Tumor Proportional Score/Combined Positive Score using immunohistochemistry were included. Clinical trials of BTC treated with chemo-ICI were included to assess PD-L1 expression on treatment response. PubMed, Embase, Web of Science, and Cochrane Library were searched for relevant studies before November 15, 2023. Methods of PD-L1 assessment, including antibody clone, cutoff for PD-L1 positivity, and anatomical subtype, were analyzed. Overall survival (OS) and objective response rates (ORRs) were the main outcomes. The generic inverse variance method and random-effect model were used to assess pooled effect sizes.
Fifty-six studies met eligibility criteria. Among 7,768 patients, pooled PD-L1 positivity was 30%. Positivity rates varied significantly by antibody clone (5H1, 58% SP142, 17%; = .02). Clinical trials reported a higher positivity rate compared with observational studies (48% 26%; < .01). Across five phase I/II clinical trials (194 patients), PD-L1 ≥1% patients tended to have a better ORR than PD-L1 <1% patients (64% 46%; = .08). In two randomized controlled trials (874 patients), PD-L1 ≥1% had a statistically significant improvement in OS (hazard ratio [HR], 0.83; < .01), while PD-L1 <1% did not (HR, 0.85; = .2).
Given the high PD-L1 positivity rate seen in this study, as well as a possible signal of predictive response for chemo-ICI treatment, PD-L1 expression should be further explored as a predictive biomarker.
据报道，胆道癌（BTC）中PD-L1阳性率为4%至76%。BTC的临床试验尚未证明PD-L1表达可作为化疗联合免疫检查点抑制剂（化疗-ICI）疗效的预测指标。本荟萃分析研究了BTC中PD-L1阳性率以及PD-L1表达与接受化疗-ICI治疗患者的预后之间的关联。
纳入采用免疫组织化学通过肿瘤比例评分/综合阳性评分报告基于组织的PD-L1表达的观察性研究或临床试验。纳入接受化疗-ICI治疗的BTC临床试验，以评估PD-L1表达对治疗反应的影响。在2023年11月15日前检索PubMed、Embase、科学网和考克兰图书馆以查找相关研究。分析了PD-L1评估方法，包括抗体克隆、PD-L1阳性的临界值和解剖亚型。总生存期（OS）和客观缓解率（ORR）为主要结局。采用通用逆方差法和随机效应模型评估合并效应量。
56项研究符合纳入标准。在7768例患者中，合并的PD-L1阳性率为30%。阳性率因抗体克隆而异（5H1为58%，SP142为17%；P = 0.02）。与观察性研究相比，临床试验报告的阳性率更高（48%对26%；P < 0.01）。在五项I/II期临床试验（194例患者）中，PD-L1≥1%的患者ORR往往高于PD-L1<1%的患者（64%对46%；P = 0.08）。在两项随机对照试验（874例患者）中，PD-L1≥1%的患者OS有统计学显著改善（风险比[HR]，0.83；P < 0.01），而PD-L1<1%的患者则无改善（HR，0.85；P = 0.2）。
鉴于本研究中观察到的高PD-L1阳性率以及化疗-ICI治疗可能的预测反应信号，应进一步探索PD-L1表达作为预测生物标志物的作用。
