Abstract：
OBJECTIVE: Our study aimed to evaluate the impact of concomitant medications on the response and survival of patients with advanced digestive tract cancer receiving an immunotherapy-antiangiogenesis combination.
METHODS: We conducted a three-center observational retrospective study of patients with advanced digestive tract cancer who received programmed death-1 (PD-1) inhibitors plus antiangiogenic agents between March 2019 and July 2022 in China. The patients had one of the three types of primary tumors: hepatocellular carcinoma (HCC), colorectal cancer (CRC), and gastric cancer (GC).
RESULTS: The study included 352 patients. The most frequently prescribed co-medications were nonsteroidal anti-inflammatory drugs (NSAIDs) (46.3%), proton pump inhibitors (PPIs) (38.0%), systemic antibiotics (33.8%), and corticosteroids (30.1%). Probiotics had a direct correlation with a higher objective response rate (ORR) (OR 2.4, 95% CI 1.2 to 4.7, p = 0.013). Patients who received PPIs for gastritis/gastroesophageal reflux disease (GERD) (HR 0.7, 95% CI 0.5 to 1.0, p = 0.045), anticoagulants (HR 0.5, 95% CI 0.3 to 0.9, p = 0.009), and probiotics (HR 0.7, 95% CI 0.5 to 1.0, p = 0.034) had longer progression-free survival (PFS). Patients who received PPIs for gastritis/GERD (HR 0.6, 95% CI 0.4 to 0.9; p = 0.009) had longer overall survival (OS), while patients receiving opioids (HR 1.5, 95% CI 1.1 to 2.0, p = 0.010) had a significantly higher risk of death.
CONCLUSIONS: Patients with advanced digestive tract cancer who were administered PPIs for gastritis/GERD indication, anticoagulants, or probiotics in combination with PD-1 inhibitors and antiangiogenic agents experienced improved clinical outcomes. However, opioid administration was linked to reduced OS in patients receiving combined therapy.
METHODS: We conducted a three-center observational retrospective study of patients with advanced digestive tract cancer who received programmed death-1 (PD-1) inhibitors plus antiangiogenic agents between March 2019 and July 2022 in China. The patients had one of the three types of primary tumors: hepatocellular carcinoma (HCC), colorectal cancer (CRC), and gastric cancer (GC).
RESULTS: The study included 352 patients. The most frequently prescribed co-medications were nonsteroidal anti-inflammatory drugs (NSAIDs) (46.3%), proton pump inhibitors (PPIs) (38.0%), systemic antibiotics (33.8%), and corticosteroids (30.1%). Probiotics had a direct correlation with a higher objective response rate (ORR) (OR 2.4, 95% CI 1.2 to 4.7, p = 0.013). Patients who received PPIs for gastritis/gastroesophageal reflux disease (GERD) (HR 0.7, 95% CI 0.5 to 1.0, p = 0.045), anticoagulants (HR 0.5, 95% CI 0.3 to 0.9, p = 0.009), and probiotics (HR 0.7, 95% CI 0.5 to 1.0, p = 0.034) had longer progression-free survival (PFS). Patients who received PPIs for gastritis/GERD (HR 0.6, 95% CI 0.4 to 0.9; p = 0.009) had longer overall survival (OS), while patients receiving opioids (HR 1.5, 95% CI 1.1 to 2.0, p = 0.010) had a significantly higher risk of death.
CONCLUSIONS: Patients with advanced digestive tract cancer who were administered PPIs for gastritis/GERD indication, anticoagulants, or probiotics in combination with PD-1 inhibitors and antiangiogenic agents experienced improved clinical outcomes. However, opioid administration was linked to reduced OS in patients receiving combined therapy.
摘要：
目的：我们的研究旨在评估合并用药对接受免疫治疗-抗血管生成联合治疗的晚期消化道癌症患者的反应和生存的影响。
方法：我们对2019年3月至2022年7月在中国接受程序性死亡-1（PD-1）抑制剂联合抗血管生成药物治疗的晚期消化道癌症患者进行了一项三中心观察性回顾性研究。患者有三种类型的原发性肿瘤之一：肝细胞癌（HCC），结直肠癌(CRC),和胃癌（GC）。
结果：该研究包括352名患者。最常用的联合用药是非甾体抗炎药（NSAIDs）（46.3%），质子泵抑制剂（PPI）（38.0%），全身抗生素（33.8%），和皮质类固醇（30.1%）。益生菌与较高的客观缓解率（ORR）直接相关（OR2.4，95％CI1.2至4.7，p=0.013）。接受PPI治疗胃炎/胃食管反流病（GERD）的患者（HR0.7，95％CI0.5至1.0，p=0.045），抗凝剂（HR0.5，95%CI0.3至0.9，p=0.009），和益生菌（HR0.7，95％CI0.5至1.0，p=0.034）具有更长的无进展生存期（PFS）。接受PPI治疗胃炎/GERD的患者（HR0.6，95％CI0.4至0.9；p=0.009）的总生存期（OS）更长，而接受阿片类药物治疗的患者(HR1.5,95%CI1.1~2.0,p=0.010)的死亡风险明显较高.
结论：接受PPI治疗胃炎/GERD适应症的晚期消化道癌症患者，抗凝剂,或益生菌联合PD-1抑制剂和抗血管生成药物的临床结局得到改善.然而,在接受联合治疗的患者中，阿片类药物的使用与OS降低有关。
方法：我们对2019年3月至2022年7月在中国接受程序性死亡-1（PD-1）抑制剂联合抗血管生成药物治疗的晚期消化道癌症患者进行了一项三中心观察性回顾性研究。患者有三种类型的原发性肿瘤之一：肝细胞癌（HCC），结直肠癌(CRC),和胃癌（GC）。
结果：该研究包括352名患者。最常用的联合用药是非甾体抗炎药（NSAIDs）（46.3%），质子泵抑制剂（PPI）（38.0%），全身抗生素（33.8%），和皮质类固醇（30.1%）。益生菌与较高的客观缓解率（ORR）直接相关（OR2.4，95％CI1.2至4.7，p=0.013）。接受PPI治疗胃炎/胃食管反流病（GERD）的患者（HR0.7，95％CI0.5至1.0，p=0.045），抗凝剂（HR0.5，95%CI0.3至0.9，p=0.009），和益生菌（HR0.7，95％CI0.5至1.0，p=0.034）具有更长的无进展生存期（PFS）。接受PPI治疗胃炎/GERD的患者（HR0.6，95％CI0.4至0.9；p=0.009）的总生存期（OS）更长，而接受阿片类药物治疗的患者(HR1.5,95%CI1.1~2.0,p=0.010)的死亡风险明显较高.
结论：接受PPI治疗胃炎/GERD适应症的晚期消化道癌症患者，抗凝剂,或益生菌联合PD-1抑制剂和抗血管生成药物的临床结局得到改善.然而,在接受联合治疗的患者中，阿片类药物的使用与OS降低有关。
