Abstract:

Objective　To explore the efficacy and safety of Furmonertinib combined with Toripalimab in the treatment of advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene mutation positivity. Methods　This study was a randomized controlled trial. A total of 164 patients with EGFR gene mutation-positive advanced NSCLC admitted to Ankang Central Hospital from February 2019 to February 2021 were selected as the study objects. They were divided into an experimental group and a control group by the random number table method, with 82 cases in each group. There were 45 males and 37 females in the experimental group, aged (63.28±6.75) years. There were 45 males and 37 females in the control group, aged (65.02±7.19) years. The basic treatment included intravenous infusion of pemetrexed at a dose of 500 mg·m^-2, once every 21 days, with 21 days as a treatment cycle. The control group received oral administration of 40 mg of Furmonertinib mesylate tablets, twice a day. On the basis of the control group, the experimental group received intravenous infusion of Toripalimab injection at a dose of 3 mg·kg^-1 every 21 days, with 21 days as a treatment cycle. After 3 cycles of treatment, the efficacy, adverse reactions, and levels of cytokeratin19 fragment antigen 21-1 (CYFRA21-1), carbohydrate antigen-199 (CA-199), CD4⁺, and CD4⁺/CD8⁺ were compared between the two groups. The survival prognosis of the two groups was compared after 2 years of follow-up. χ² test and t test were used. Results　During the treatment period, 5 cases were lost to follow-up in the experimental group, resulting in data collection from 77 cases; in the control group, 8 cases were lost to follow-up, resulting in data collection from 74 cases. After 3 cycles of treatment, the levels of CYFRA21-1 in the experimental group and the control group were (5.18±1.62) µg·L^-1 and (7.03±1.89) µg·L^-1, the levels of CA-199 were (36.71±6.93) U·ml^-1 and (49.46±8.02) U·ml^-1, the levels of CD4⁺ were (39.06±5.32)% and (31.92±4.15)%, and the levels of CD4⁺/CD8⁺ were (1.48±0.53) and (1.05±0.48), with statistically significant differences between the two groups (t=6.467, 10.465, 9.171, and 5.219, all P<0.05). The disease control rates of the experimental group and the control group were 88.31% (68/77) and 75.68% (56/74), respectively, with a statistically significant difference between the two groups (χ²=4.103, P=0.043). By the end of follow-up, 30 patients in the experimental group died, and the median progression-free survival (PFS) was 19 months, which did not reach the median overall survival (OS). In the control group, 35 patients died, and the median PFS was 15 months, which did not reach the median OS. There was a statistically significant difference in the PFS between the two groups (Log-rank χ²=2.608, P=0.031). Conclusion　In the treatment of EGFR gene mutation-positive advanced NSCLC, Furmonertinib combined with Toripalimab can improve the disease control rate, reduce the levels of tumor markers (CYFRA21-1 and CA-199), and prolong the PFS, which does not increase the incidence of adverse drug reactions, with good safety.

Key words:

Non small cell lung cancer, Advanced stage, Epidermal growth factor receptor-tyrosine kinase inhibitor, Furmonertinib, Toripalimab

摘要：

目的　探讨伏美替尼联合特瑞普利单抗治疗表皮生长因子受体（EGFR）基因突变阳性晚期非小细胞肺癌（NSCLC）的疗效及安全性。方法　本研究为随机对照试验。选取2019年2月至2021年2月安康市中心医院收治的164例EGFR基因突变阳性晚期NSCLC为研究对象。采用随机数字表法将其分为试验组和对照组，每组82例。试验组男45例，女37例；年龄（63.28±6.75）岁。对照组男45例，女37例；年龄（65.02±7.19）岁。基础治疗：静脉滴注培美曲塞500 mg·m^-2，间隔21 d治疗1次，21 d为1个治疗周期。对照组口服甲磺酸伏美替尼片40 mg·次^-1，2次·d^-1。试验组在对照组基础上，静脉滴注特瑞普利单抗注射液3 mg·kg^-1，间隔21 d治疗1次，21 d为1个治疗周期。治疗3个周期后，比较两组的疗效、不良反应、细胞角质蛋白19片段抗原21-1（CYFRA21-1）、糖类抗原-199（CA-199）、CD4⁺、CD4⁺/CD8⁺。随访2年比较两组的生存预后。采用χ²检验、t检验。结果　治疗期间试验组失访5例，收集试验数据77例；对照组失访8例，收集试验数据74例。治疗3个周期后，试验组和对照组的CYFRA21-1分别为（5.18±1.62）µg·L^-1和（7.03±1.89）µg·L^-1，CA-199分别为（36.71±6.93）U·ml^-1和（49.46±8.02）U·ml^-1，CD4⁺分别为（39.06±5.32）%和（31.92±4.15）%，CD4⁺/CD8⁺分别为（1.48±0.53）和（1.05±0.48），两组比较差异均有统计学意义（t=6.467、10.465、9.171、5.219，均P<0.05）。试验组和对照组的疾病控制率分别为88.31%（68/77）、75.68%（56/74），两组比较差异有统计学意义（χ²=4.103，P=0.043）。截至随访结束，试验组死亡30例，中位无进展生存期（PFS）19个月，未达到中位总生存期（OS）；对照组死亡35例，中位PFS 15个月，未达到中位OS；两组PFS比较，差异有统计学意义（Log-rank χ²=2.608，P=0.031）。结论　伏美替尼联合特瑞普利单抗治疗EGFR基因突变阳性晚期NSCLC，能够提高疾病控制率，降低肿瘤标志物CYFRA21-1、CA-199水平，延长PFS，未明显增加药物不良反应发生率，安全性良好。

关键词:

非小细胞肺癌, 晚期, 表皮生长因子受体-酪氨酸激酶抑制剂, 伏美替尼, 特瑞普利单抗