不可切除性混合型肝癌靶向治疗与化疗的疗效评价：一项系统综述和荟萃分析

Curative Effect Evaluation of Targeted Therapy and Chemotherapy for Non-Resectable Combined Hepatocellular-Cholangiocarcinoma: A Systematic Review and Meta-Analysis

摘要: 肝细胞与胆管细胞混合型肝癌是一种罕见的原发性肝脏恶性肿瘤，针对其不可切除晚期患者的全身治疗策略尚未标准化。本荟萃分析纳入6项研究共417例患者(其中不可切除者360例)，比较一线靶向治疗与化疗的疗效。结果显示，总体客观缓解率(ORR)为21% (95% CI: 15%~29%)，疾病控制率(DCR)为53% (95% CI: 42%~65%)，表明系统治疗具有抗肿瘤活性。亚组分析显示，化疗在诱导肿瘤缩小方面优于靶向治疗(ORR: 25% vs. 13%)，且化疗组中位总生存期显著延长(合并均数差−5.24个月，95% CI:−8.54至−1.95)。但两组在ORR、DCR、1~3年生存率及无进展生存期方面的差异均无统计学意义。此外，含铂化疗方案与非含铂方案相比，ORR未见显著优势(OR = 1.91, 95% CI: 0.50~7.37)。对于不可切除性混合型肝癌，靶向治疗与化疗均显示出一定的抗肿瘤活性，且在疾病控制方面具有潜在价值。相较于靶向治疗，化疗在诱导肿瘤客观缓解方面表现出更优的短期疗效，并可能转化为更持久的长期生存获益。尽管既往临床实践倾向于选择含铂化疗方案，但本分析中，含铂方案与非含铂方案相比，在客观缓解率上未观察到显著的统计学差异。

Abstract: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer, and systemic treatment strategies for patients with unresectable advanced disease have yet to be established. This meta-analysis included 6 studies involving 417 patients (360 with unresectable disease) to compare the efficacy of first-line targeted therapy to chemotherapy. The overall objective response rate (ORR) was 21% (95% CI: 15%~29%), while the disease control rate (DCR) was 53% (95% CI: 42%~65%), indicating that systemic therapy has antitumor activity. Subgroup analysis revealed that chemotherapy outperformed targeted therapy in terms of tumor shrinkage (ORR: 25% vs. 13%), and chemotherapy patients had a significantly longer median overall survival (pooled mean difference: −5.24 months, 95% CI: −8.54 to −1.95). Nevertheless, ORR, DCR, 1-, 2-, or 3-year survival rates, and progression-free survival did not differ statistically significantly between the two groups. Additionally, platinum-based chemotherapy did not significantly improve ORR when compared to non-platinum regimens (OR = 1.91, 95% CI: 0.50~7.37). For unresectable cHCC-CCA, both targeted therapy and chemotherapy demonstrate certain antitumor activity and potential value in disease control. Chemotherapy has a higher short-term efficacy in inducing an objective tumor response than targeted therapy, which may translate into longer-term survival benefits. Although clinical practice has tended to prefer platinum‑based chemotherapy, no statistically significant difference in ORR was observed between platinum‑based and non‑platinum regimens in this analysis.