年轻患者在转移性胃肠道癌中接受免疫检查点抑制剂联合治疗的疗效不佳。
Young patients show poor efficacy for immune checkpoint inhibitor combined therapy in metastatic gastrointestinal cancers.
作者信息
Wang Yingnan, Zhang Shasha, Zhang Fengbin, Wang Lei, Wu Chensi, Zhang Xiaoyun, Zhang Ruixing, Guo Zhanjun
机构信息
Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Rheumatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
出版信息
Front Oncol. 2023 May 3;13:1155019. doi: 10.3389/fonc.2023.1155019. eCollection 2023.
BACKGROUND
The impact of age on the efficacy and safety of immunotherapy remains controversial. The previous studies simply classified patients into younger and older groups, which might not reflect the real impact of young age on immunotherapy efficacy. The current study aimed to explore the efficacy and safety of immune checkpoint inhibitor (ICI) combined therapy in young (aged 18-44 years), middle-aged (aged 45-65 years), and old (aged >65 years) patients with metastatic gastrointestinal cancers (GICs), and further determine the role of immunotherapy in young patients.
METHODS
Patients with metastatic GIC including esophageal cancer (EC), gastric cancer (GC), hepatocellular cancer (HCC), and biliary tract cancer (BTC) who received ICI combination therapy were enrolled, divided into young (aged 18-44 years), middle-aged (aged 45-65 years), and old (aged >65 years) groups. The clinical characteristics, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) were compared among three groups.
RESULTS
A total of 254 patients were finally included, with 18, 139, and 97 cases in the young (aged 18-44 years), middle-aged (aged 45-65 years), and old (aged >65 years) groups, respectively. Compared to middle-aged and old patients, young patients had lower DCR (all < 0.05) and also had inferior PFS ( < 0.001) and OS ( 0.017). The multivariate analyses showed that young age was an independent prognostic factor for PFS [hazard ratio (HR) 3.474, 95% confidence interval (CI) 1.962-6.150, < 0.001] and OS (HR 2.740, 95% CI 1.348-5.570, = 0.005). Subsequent safety analyses referring to irAEs demonstrated no significant differences for distribution frequency among each age group (all > 0.05), whereas patients with irAEs displayed better DCR ( = 0.035) and PFS ( = 0.037).
CONCLUSION
Younger GIC patients (aged 18-44 years) showed poor efficacy for ICI combined therapy, and irAEs could be used as a clinical biomarker to predict ICI efficacy in metastatic GIC patients.
背景
年龄对免疫治疗疗效和安全性的影响仍存在争议。以往研究简单地将患者分为年轻组和老年组，可能无法反映年轻对免疫治疗疗效的真实影响。本研究旨在探讨免疫检查点抑制剂（ICI）联合治疗在年轻（18 - 44岁）、中年（45 - 65岁）和老年（>65岁）转移性胃肠道癌（GIC）患者中的疗效和安全性，并进一步确定免疫治疗在年轻患者中的作用。
方法
纳入接受ICI联合治疗的转移性GIC患者，包括食管癌（EC）、胃癌（GC）、肝细胞癌（HCC）和胆管癌（BTC），分为年轻（18 - 44岁）、中年（45 - 65岁）和老年（>65岁）组。比较三组患者的临床特征、客观缓解率（ORR）、疾病控制率（DCR）、无进展生存期（PFS）、总生存期（OS）和免疫相关不良事件（irAE）。
结果
最终共纳入254例患者，年轻（18 - 44岁）组18例，中年（45 - 65岁）组139例，老年（>65岁）组97例。与中年和老年患者相比，年轻患者的DCR较低（均<0.05），PFS（<0.001）和OS也较差（0.017）。多因素分析显示，年轻是PFS的独立预后因素[风险比（HR）3.474，95%置信区间（CI）1.962 - 6.150，<0.001]和OS的独立预后因素（HR 2.740，95%CI 1.348 - 5.570，=0.005）。随后针对irAE的安全性分析表明，各年龄组间分布频率无显著差异（均>0.05），而发生irAE的患者显示出更好的DCR（=0.035）和PFS（=0.037）。
结论
年轻的GIC患者（18 - 44岁）接受ICI联合治疗疗效不佳，irAE可作为预测转移性GIC患者ICI疗效的临床生物标志物。
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