达可替尼联合达卡瑞利珠单抗治疗EGFR突变局部晚期NSCLC的临床疗效及安全性研究

Clinical efficacy and safety of Dakotinib combined with Carilizumab in the treatment of EGFR-mutated locally advanced non-small cell lung cancer

目的探究达可替尼联合卡瑞利珠单抗(Cam)治疗表皮生长因子受体(EGFR)突变局部晚期非小细胞肺癌(NSCLC)的临床疗效及安全性。方法选取2022年1月至2023年11月濮阳市安阳地区医院收治的98例EGFR突变局部晚期NSCLC患者纳入研究,采用简单随机化法分为对照组和研究组各49例。对照组患者给予达可替尼治疗,研究组患者给予达可替尼联合Cam治疗,21 d为一个周期,均治疗4个周期。比较两组患者的治疗效果,以及治疗前、治疗2个周期、治疗4个周期后的T淋巴细胞亚群(CD3+、CD4+、CD4+/CD8+)、血管生长因子[血小板衍生生长因子(PDGF)、血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)]、预后相关标志物[微小RNA(miRNA)-137-3p、miR-1255b-5p、miR-379-5p]、体能状态[卡氏功能状态(KPS)]和生存质量[肺癌患者生存质量评定量表(FACT-L)],并比较两组患者治疗期间的不良反应发生率。结果研究组患者的客观缓解率(ORR)为85.71%,明显高于对照组的67.35%,差异有统计学意义(P<0.05);治疗2个周期、4个周期后,研究组患者的外周血CD3+、CD4+、CD4+/CD8+水平分别为(53.63±4.58)%和(51.25±4.13)%、(35.47±3.12)%和(33.96±2.83)%、1.59±0.21和1.45±0.17,明显高于对照组的(51.45±4.23)%和(49.17±4.19)%、(33.82±3.07)%和(32.42±2.91)%、1.47±0.20和1.37±0.19,差异均有统计学意义(P<0.05);治疗2个周期、4个周期后,研究组患者的血清PDGF、VEGF、bFGF水平分别为(1.58±0.18)ng/mL和(1.13±0.09)ng/mL、(31.38±3.74)ng/L和(23.19±2.41)ng/L、(184.99±26.12)pg/mL、(135.39±19.24)pg/mL,明显低于对照组的(1.69±0.19)ng/mL和(1.21±0.13)ng/mL、(34.12±3.81)ng/L和(27.36±2.68)ng/L、(207.16±27.73)pg/mL和(172.61±23.85)pg/mL,差异均有统计学意义(P<0.05);治疗2个周期、4个周期后,研究组患者的血清miR-137-3p、miR-379-5p、miR-1255b-5p水平分别为0.68±0.15和0.71±0.19、0.53±0.12和0.65±0.15、0.40±0.09和0.49±0.11,明显高于对照组的0.55±0.14和0.63±0.18、0.46±0.11和0.57±0.13、0.35±0.08和0.44±0.10,差异均有统计学意义(P<0.05);治疗2个周期、4个周期后,研究组患者的KPS评分、FACT-L评分分别为(80.01±2.67)分和(82.64±2.79)分、(84.29±8.14)分和(102.93±9.64)分,明显高于对照组的(78.39±2.65)分和(80.92±2.73)分、(74.05±7.86)分和(85.24±8.19)分,差异均有统计学意义(P<0.05);治疗期间,研究组患者的不良反应总发生率为26.53%,略低于对照组的40.82%,但差异无统计学意义(P>0.05)。结论达可替尼联合Cam治疗EGFR突变局部晚期NSCLC患者的疗效显著,其可改善患者免疫功能,抑制肿瘤血管生长因子,有助于改善患者预后,提高患者生存质量及体能状态,且安全性良好。

Objective To explore the clinical efficacy and safety of Dakotinib combined with Carrilizumab(Cam)in the treatment of epidermal growth factor receptor(EGFR)mutated locally advanced nonsmall cell lung cancer(NSCLC).Methods From January 2022 to November 2023,98 patients of locally advanced NSCLC with EGFR mutations were selected from Anyang District Hospital in Puyang City.They were randomly divided into a control group and a study group using a simple randomization method,with 49 patients in each group.Patients in the control group were treated with Dacomitinib,while those in the study group were treated with Dacomitinib in combination with Cam,with 21 d as one cycle,all for 4 cycles.The therapeutic effects were compared between the two groups,as well as the T lymphocyte subsets(CD3+,CD4+,and CD4+/CD8+),vascular growth factors(plateletderived growth factor,PDGF;vascular endothelial growth factor,VEGF;basic fibroblast growth factor,bFGF),prognosisrelated markers(miR1373p,miR1255b5p,miR3795p),physical status(Karnofsky Performance Status,KPS),quality of life(Functional Assessment of Cancer TherapyLung,FACTL)before treatment and after 2 cycles,4 cycles of treatment.The incidence of adverse reactions during treatment were also compared.Results The objective response rate(ORR)of the study group was 85.71%,which was significantly higher than 67.35%of the control group(P<0.05).After 2 cycles and 4 cycles of treatment,the levels of CD3+,CD4+,and CD4+/CD8+in the peripheral blood of patients in the study group were(53.63±4.58)%and(51.25±4.13)%,(35.47±3.12)%and(33.96±2.83)%,and 1.59±0.21 and 1.45±0.17,respectively,which were significantly higher than(51.45±4.23)%and(49.17±4.19)%,(33.82±3.07)%and(32.42±2.91)%,and 1.47±0.20 and 1.37±0.19 in the control group(P<0.05).After 2 cycles and 4 cycles of treatment,the levels of serum PDGF,VEGF,and bFGF in the study group were(1.58±0.18)ng/mL and(1.13±0.09)ng/mL,(31.38±3.74)ng/L and(23.19±2.41)ng/L,and(184.99±26.12)pg/mL and(135.39±19.24)pg/mL,respectively,which were significantly lower than(1.69±0.19)ng/mL and(1.21±0.13)ng/mL,(34.12±3.81)ng/L and(27.36±2.68)ng/L,and(207.16±27.73)pg/mL and(172.61±23.85)pg/mL in the control group(P<0.05).After 2 cycles and 4 cycles of treatment,the levels of serum miR1373p,miR3795p,and miR1255b5p in the study group were 0.68±0.15 and 0.71±0.19,0.53±0.12 and 0.65±0.15,and 0.40±0.09 and 0.49±0.11,respectively,which were significantly higher than 0.55±0.14 and 0.63±0.18,0.46±0.11 and 0.57±0.13,and 0.35±0.08 and 0.44±0.10 in the control group(P<0.05).After 2 cycles and 4 cycles of treatment,the KPS scores,FACTL scores of patients in the study group were(80.01±2.67)points and(82.64±2.79)points,(84.29±8.14)points and(102.93±9.64)points,respectively,which were significantly higher than(78.39±2.65)points and(80.92±2.73)points,(74.05±7.86)points and(85.24±8.19)points in the control group(P<0.05).During the treatment period,the total incidence of adverse reactions in the study group was 26.53%,slightly lower than the control group's 40.82%(P>0.05).Conclusion Dakotinib combined with Cam has significant therapeutic effects on patients with EGFRmutated locally advanced nonsmall cell lung cancer.It can improve the patient's immune function,inhibit tumor angiogenesis factors,help improve the patient's prognosis,enhance their quality of life and physical condition,and has good safety.