Department of Gastrointestinal Oncology , Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) , Peking University Cancer Hospital and Institute , Beijing , China.
Department of Medical Oncology , National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
Hepatology. 2023 Jan 1;77(1):65-76. doi: 10.1002/hep.32548. Epub 2022 Aug 18.
We evaluated the efficacy and safety of the antiangiogenic tyrosine kinase inhibitor anlotinib plus TQB2450, a programmed death-ligand 1 inhibitor in pretreated advanced biliary tract cancers (BTCs).
In this pooled analysis of two single-center, phase Ib clinical trials (TQB2450-Ib-05 and TQB2450-Ib-08 trials), 66 patients with advanced BTCs who had progressed or declined or were ineligible for first-line chemotherapy were included. With the treatment of anlotinib plus TQB2450, two patients achieved complete response, and 12 had a partial response assessed by Response Evaluation Criteria in Solid Tumors 1.1, yielding an objective response rate of 21.21%, a disease control rate (DCR) of 72.73%, and a clinical benefit rate (CBR) of 42.42%. With a median follow-up of 19.68 months, median progression-free survival (PFS) and overall survival (OS) were 6.24 (95% confidence interval [CI], 4.11-8.25) and 15.77 (95% CI, 10.74-19.71) months, respectively. Adverse events (AEs) were reported in 64 (96.97%) patients, and the most common grade 3 or worse treatment-related AEs included elevated levels of aspartate aminotransferase (7.58%), alanine aminotransferase (6.06%), and hypertension (6.06%). Patients with high tumor mutational burden (TMB; ≥5 mutations/Mbp) had a better CBR (70.8% vs. 22.2%), longer OS (14.32 vs. 9.64 months), and a trend toward longer PFS (7.03 vs. 4.06 months). Patients with kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutations showed a lower CBR (12.5% vs. 58.8%) and shorter PFS (2.02 vs. 6.80 months) and OS (10.53 vs. 13.13 months).
Anlotinib combined with TQB2450 showed promising efficacy and was well tolerated in advanced BTCs. KRAS mutation and high TMB might serve as predictors of treatment efficacy.
我们评估了抗血管生成的酪氨酸激酶抑制剂安罗替尼联合 TQB2450（一种程序性死亡配体 1 抑制剂）在治疗经治晚期胆道癌（BTC）中的疗效和安全性。
在这两项单中心、Ib 期临床试验（TQB2450-Ib-05 和 TQB2450-Ib-08 试验）的汇总分析中，纳入了 66 例接受过一线化疗进展、衰退或不适合的晚期 BTC 患者。接受安罗替尼联合 TQB2450 治疗后，2 例患者达到完全缓解，12 例患者根据实体瘤反应评价标准 1.1 评估为部分缓解，客观缓解率为 21.21%，疾病控制率（DCR）为 72.73%，临床获益率（CBR）为 42.42%。中位随访 19.68 个月时，中位无进展生存期（PFS）和总生存期（OS）分别为 6.24（95%置信区间[CI]，4.11-8.25）和 15.77（95%CI，10.74-19.71）个月。64 例（96.97%）患者报告了不良事件（AE），最常见的 3 级或更高级别的治疗相关 AE 包括天冬氨酸转氨酶升高（7.58%）、丙氨酸转氨酶升高（6.06%）和高血压（6.06%）。高肿瘤突变负荷（TMB；≥5 突变/Mbp）的患者具有更好的 CBR（70.8%比 22.2%）、更长的 OS（14.32 比 9.64 个月）和更长的 PFS 趋势（7.03 比 4.06 个月）。KRAS 突变的患者 CBR 较低（12.5%比 58.8%），PFS（2.02 比 6.80 个月）和 OS（10.53 比 13.13 个月）较短。
安罗替尼联合 TQB2450 在晚期 BTC 中显示出有希望的疗效且耐受良好。KRAS 突变和高 TMB 可能是治疗效果的预测因子。
