[摘 要] 目的：观察聚乙二醇化重组人粒细胞集落刺激因子（PEG-rhG-CSF）联合信迪利单抗和含铂双药化疗对晚期非鳞非 小细胞肺癌（NSCLC）的疗效及安全性。方法: 选取2020年1月至2021年12月在济南市第八人民医院肿瘤科收治的187例Ⅳ期 NSCLC患者为对象行前瞻性随机对照研究，用随机数字表法将患者分为试验组（PEG-rhG-CSF + 信迪利单抗 + 培美曲塞 + 铂 类）94例，对照组（信迪利单抗 + 培美曲塞 + 铂类）93例。随访2年，对比两组患者近期临床疗效、无进展生存期（PFS）、总生存期 （OS）和治疗期间不良反应。结果: 试验组客观缓解率（ORR）高于对照组[61.63%（53/86） vs 45.35%（39/86），χ2 = 4.554， P = 0.032 8]。两组的疾病控制率（DCR）差异无统计学意义[87.21%（75/86） vs 81.40%（70/86）,χ2 = 1.092，P = 0.079 1]。试验组中 位PFS明显优于对照组[10.6个月 vs 9.1个月；HR = 0.72，95% C（I 0.51，0.99）；χ2 = 3.8998，P = 0.048 3]。试验组的中位OS明显优 于对照组[未达到 vs 22.6个月；HR = 0.63，95%C（I 0.42，0.95）；χ2 = 4.7716，P = 0.028 9]。预设亚组包括：年龄 ＜ 65岁（是或否）、性 别、吸烟史（有或无）、PD-L1 TPS ≥ 1%（是或否）、铂类药物（顺铂或卡铂）、ECOG评分（0分或1分）均观察到一致的试验组OS获 益趋势（HR均 < 1）。试验组中性粒细胞减少发生率低于对照组（P < 0.000 1），发热发生率高于对照组（P = 0.045 1）。两组恶心、 贫血、劳累、便秘、腹泻、食欲下降、呕吐、咳嗽、呼吸困难、外周水肿、肌肉酸痛、皮疹、血小板减少、甲状腺功能减退、免疫性肺炎、 免疫性肠炎不良反应发生率比较，差异均无统计学意义（均P > 0.05）。结论: 晚期非鳞NSCLC患者采用PEG-rhG-CSF联合信迪 利单抗 + 培美曲塞 + 铂类可能提高近期临床疗效和远期生存，降低中性粒细胞减少发生率，安全性可控。

[Abstract] Objective: To evaluate the efficacy and safety of Pegylated Recombinant Human Granulocyte Colony-Stimulating Factor (PEG-rhG-CSF) combined with sintilimab and platinum-based chemotherapy in the treatment of advanced non-squamous non-small cell lung cancer (NSCLC). Methods: A prospective, randomized controlled study was conducted on 187 patients with stage Ⅳ nonsquamous NSCLC admitted to the Department of Oncology at Jinan Eighth People's Hospital from January 2020 to December 2021. The patients were randomly divided into an experimental group (PEG-rhG-CSF + sintilimab + pemetrexed + platinum; n = 94) or a control group (sintilimab + pemetrexed + platinum, n = 93) using a random number table method. All patients were followed for two years. Short-term clinical efficacy, progression-free survival (PFS), overall survival (OS), and treatment-related adverse reactions were compared between the two groups. Results: The objective response rate (ORR) in the experimental group was higher than that in the control group (61.63% [53/86] vs 45.35% [39/86], χ2 = 4.554, P = 0.032 8). The disease control rate (DCR) did not differ significantly between the two groups (87.21% [75/86] vs 81.40% [70/86], χ2 = 1.092, P = 0.079 1). The median progression-free survival (PFS) in the experimental group was significantly longer than that in the control group [10.6 months vs 9.1 months; HR = 0.72; χ2 = 3.899 8, P = 0.048 3]. The median overall survival (OS) in the experimental group was also significantly longer than that in the control group [not reached vs 22.6 months; HR = 0.63; χ2 = 4.7716, P = 0.028 9]. Consistent OS benefits (all HR < 1) were observed in the predefined subgroup analyses, including age < 65 years (yes or no), gender, smoking history (yes or no), PD-L1 TPS ≥ 1% (yes or no), platinumbased drugs (cisplatin or carboplatin), and ECOG PS score (0 or 1). The incidence of neutropenia was significantly lower in the experimental group than that in the control group (P < 0.000 1), while the incidence of fever was significantly higher (P = 0.045 1). No significant differences were observed between the two groups in nausea, anemia, fatigue, constipation, diarrhea, decreased appetite, vomiting, cough, dyspnea, peripheral edema, muscle pain, rash, thrombocytopenia, hypothyroidism, immune pneumonitis, or immunerelated colitis (all P > 0.05). Conclusion： The combination of PEG-rhG-CSF with sintilimab, pemetrexed, and platinum-based chemotherapy in advanced non-squamous NSCLC patients may improve short-term clinical efficacy and long-term survival, reduce the incidence of neutropenia, and maintain controllable safety.

[基金项目] 山东省医学会临床科研项目-齐鲁专项课题（No. YXH2022ZX02046）