Abstract:

Objective　To explore the efficacies and safeties of furmonertinib and gefitinib in the treatment of advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) sensitive mutations. Methods　This study was a prospective, randomized, controlled, and single-center clinical study. A total of 90 patients with advanced NSCLC admitted to Shangluo Central Hospital from April 2021 to April 2022 were selected and were divided into an experimental group and a control group according to the random number table method. In the experimental group, 45 cases were screened, 2 cases were excluded, and 43 cases were finally included in the analysis, including 29 males and 14 females, aged (51.79±6.28) years, and 43 cases of adenocarcinoma. In the control group, 45 cases were screened, 3 cases were excluded, and 42 cases were finally included in the analysis, including 26 males and 16 females, aged (52.06±5.41) years, and 42 cases of adenocarcinoma. Both groups were treated with pemetrexed 500 mg/m² intravenously, once every 21 days, on the first day of each treatment cycle. The control group was treated with gefitinib tablets, 250 mg each time, once a day, 21 days as 1 treatment cycle. The experimental group was treated with oral furmonertinib mesylate tablets, 40 mg each time, twice a day, 21 days as 1 treatment cycle. Both groups were treated for 3 cycles. The carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), cytokeratinin-19 fragment antigen 21-1 (CYFRA21-1), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), efficacy, and safety were compared between the two groups. The patients were followed up for 18 months, and the survival prognosis was recorded. Independent sample t test, paired t test, and χ² test were used. Results　After treatment, the total effective rates of the experimental group and the control group were 69.77% (30/43) and 47.62% (20/42), respectively, with a statistically significant difference (χ²=4.303, P=0.038). After treatment, the CEA levels in the experimental group and the control group were (20.21±5.72) and (25.31±4.16) µg/L, the CA19-9 levels were (26.85±3.92) and (29.62±4.15) µg/L, the CYFRA21-1 levels were (2.61±0.76) and (3.62±0.91) µg/L, the MMP-9 levels were (102.86±20.37) and (117.41±22.06) µg/L, and the TIMP-1 levels were (608.31±60.43) and (635.93±61.15) µg/L, with statistically significant differences (all P<0.05). The total incidence of adverse drug reactions in the experimental group and the control group were 39.53% (17/43) and 30.95% (13/42), respectively (χ²=0.685, P=0.408). At the end of follow-up, 2 patients in the experimental group were lost to follow-up, the median progression-free survival (PFS) was 8 months, and 8 patients died. In the control group, 2 patients were lost to follow-up, the median PFS was 14 months, and 17 patients died. Median overall survival (OS) was not achieved in both groups, and the difference in the OS survival curve between the two groups was statistically significant (Log-rank χ²=4.939, P=0.026). Conclusion　Compared to gefitinib, furmonertinib is more helpful in improving the disease remission rate and prolonging the PFS and OS in the treatment of advanced NSCLC, with good safety.

Key words:

Non-small cell lung cancer, Advanced stage, Epidermal growth factor receptor, Epidermal growth factor receptor tyrosine kinase inhibitor, Therapeutic effect, Survival

摘要：

目的　探究伏美替尼与吉非替尼治疗表皮生长因子受体（EGFR）敏感突变的晚期非小细胞肺癌（NSCLC）的疗效和安全性。方法　本研究采用前瞻性、随机、对照、单中心临床研究方法设计。选择2021年4月至2022年4月商洛市中心医院接诊的90例晚期NSCLC患者，按照随机数字表法分为试验组和对照组。试验组筛选45例，剔除2例，最终43例纳入分析，其中男性29例，女14例，年龄（51.79±6.28）岁，腺癌43例；对照组筛选45例，剔除3例，最终42例纳入分析，其中男性26例，女16例，年龄（52.06±5.41）岁，腺癌42例。两组患者均静脉滴注培美曲塞500 mg/m²，1次/21 d，每个治疗周期首日用药。对照组口服吉非替尼片250 mg/次，1次/d，21 d为1个治疗周期；试验组口服甲磺酸伏美替尼片40 mg/次，2次/d，21 d为1个治疗周期。两组均维持治疗3个周期。比较两组的癌胚抗原（CEA）、糖类抗原19-9（CA19-9）、细胞角质蛋白19片段抗原21-1（CYFRA21-1）、基质金属蛋白酶-9（MMP-9）、基质金属蛋白酶抑制蛋白-1（TIMP-1）水平及临床疗效、安全性。随访18个月，记录生存预后。采用独立样本t检验、配对t检验、χ²检验。结果　治疗后，试验组和对照组的总有效率分别为69.77%（30/43）和47.62%（20/42），差异有统计学意义（χ²=4.303，P=0.038）。治疗后，试验组和对照组的CEA水平分别为（20.21±5.72）µg/L、（25.31±4.16）µg/L，CA19-9水平分别为（26.85±3.92）µg/L、（29.62±4.15）µg/L，CYFRA21-1水平分别为（2.61±0.76）µg/L、（3.62±0.91）µg/L，MMP-9水平分别为（102.86±20.37）µg/L、（117.41±22.06）µg/L，TIMP-1水平分别为（608.31±60.43）µg/L、（635.93±61.15）µg/L，差异均有统计学意义（均P<0.05）。试验组和对照组的总药物不良反应发生率分别为39.53%（17/43）和30.95%（13/42）（χ²=0.685，P=0.408）。随访结束，试验组失访2例，中位无进展生存期（PFS）8个月，死亡8例；对照组失访2例，中位PFS 14个月，死亡17例。两组均未达到中位总生存期（OS），两组OS生存曲线比较，差异有统计学意义（Log-rank χ²=4.939，P=0.026）。结论　相比于吉非替尼，伏美替尼治疗晚期NSCLC更有助于提高疾病缓解率，延长PFS和OS，安全性良好。

关键词:

非小细胞肺癌, 晚期, 表皮生长因子受体, 表皮生长因子受体-酪氨酸激酶抑制剂, 疗效, 生存