Abstract:

Objective　To investigate the efficacy and safety of Osimertinib combined with Savolitinib as second-line therapy for T790M mutation-positive metastatic non-small cell lung cancer (NSCLC) during treatment with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Methods　A total of 94 patients with metastatic NSCLC with T790M mutation during EGFR-TKI treatment in Ankang People's Hospital from January 2021 to January 2022 were selected. The patients were divided into a study group (47 cases) and a control group (47 cases) by the random number table method. During the treatment period, 7 cases were lost to follow-up and 40 cases were enrolled in the study group. In the control group, 9 cases were lost to follow-up, and 38 cases were enrolled. In the control group, there were 24 males and 14 females, aged (60.32±5.71) years, with a body mass index (BMI) of (18.06±1.61) kg/m². There were 27 males and 13 females in the study group, aged (61.05±6.64) years, with a BMI of (18.13±1.54) kg/m². The control group was treated with Osimertinib, and the study group was treated with Savolitinib on the basis of the control group. After 3 months of treatment, the efficacy and adverse reactions of the two groups were compared. The serum levels of carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9) were compared between the two groups before and after treatment. The median progression-free survival (PFS) and median overall survival (OS) were recorded after 2 years of follow-up. Independent sample t test, paired t test, χ² test, Kaplan-Meier analysis, and Log-rank test were used. Results　After treatment, the levels of CEA [(65.30±14.29) μg/L], CYFRA21-1 [(1.62±0.69) μg/L], VEGF [(381.04±27.64) ng/L], and MMP-9 [(151.98±25.47) μg/L] in the study group were lower than those in the control group [(73.59±16.03) μg/L, (2.57±0.76) μg/L, (396.61±26.51) ng/L, and (169.07±26.54) μg/L], with statistically significant differences (all P<0.05). The disease control rate [85.00% (34/40)] and objective response rate [62.50% (25/40)] of the study group were higher than those of the control group [65.79% (25/38) and 39.47% (15/38)], with statistically significant differences (both P<0.05). There was no statistically significant difference in the total incidence of adverse drug reactions between the two groups (P>0.05). There were statistically significant differences in the PFS and OS between the two groups (both P<0.05). Conclusion　Osimertinib combined with Savolitinib as second-line therapy for metastatic NSCLC with T790M mutation during EGFR-TKI treatment helps to improve the disease control rate and prolong the patients' survival, with good safety.

Key words:

Metastatic non-small cell lung cancer, Epidermal growth factor receptor-tyrosine kinase inhibitor, T790M mutation, Osimertinib,  , Savolitinib

摘要：

目的　探讨奥希替尼联合赛沃替尼二线治疗表皮生长因子受体-酪氨酸激酶抑制剂（EGFR-TKI）治疗期间T790M突变的转移性非小细胞肺癌（NSCLC）的效果及安全性。方法　选取2021年1月至2022年1月安康市人民医院接收的EGFR-TKI治疗期间T790M突变的转移性NSCLC患者94例。采用随机数字表法将患者分为研究组（47例）和对照组（47例）。治疗期间研究组失访7例，最终入组40例；对照组失访9例，最终入组38例。对照组男24例，女14例；年龄（60.32±5.71）岁；体重指数（BMI）（18.06±1.61）kg/m²；采用奥希替尼治疗。研究组男27例，女13例；年龄（61.05±6.64）岁；BMI（18.13±1.54）kg/m²；在对照组基础上，采用赛沃替尼治疗。治疗3个月后，比较两组的疗效和不良反应；比较两组治疗前后的血清癌胚抗原（CEA）、细胞角质蛋白19片段抗原21-1（CYFRA21-1）、血管内皮生长因子（VEGF）、基质金属蛋白酶-9（MMP-9）水平。治疗后随访2年，记录两组的中位无进展生存期（PFS）和中位总生存期（OS）。采用独立样本t检验、配对t检验、χ²检验、Kaplan-Meier分析、Log-rank检验。结果　治疗后，研究组CEA［（65.30±14.29）μg/L］、CYFRA21-1［（1.62±0.69）μg/L］、VEGF［（381.04±27.64）ng/L］、MMP-9［（151.98±25.47）μg/L］水平均低于对照组［（73.59±16.03）μg/L、（2.57±0.76）μg/L、（396.61±26.51）ng/L、（169.07±26.54）μg/L］，差异均有统计学意义（均P<0.05）。研究组的疾病控制率［85.00%（34/40）］、客观缓解率［62.50%（25/40）］均高于对照组［65.79%（25/38）、39.47%（15/38）］，差异均有统计学意义（均P<0.05）。两组药物不良反应总发生率比较，差异无统计学意义（P>0.05）。两组PFS、OS比较，差异均有统计学意义（均P<0.05）。结论　奥希替尼联合赛沃替尼二线治疗EGFR-TKI治疗期间T790M突变的转移性NSCLC，有助于提高疾病控制率，延长患者的生存期，且安全性良好。

关键词:

转移性非小细胞肺癌, 表皮生长因子受体-酪氨酸激酶抑制剂, T790M突变, 奥希替尼, 赛沃替尼