Efficacy and prognosis comparison of first-line treatment with EGFR-TKI versus chemotherapy for non-small cell lung cancer patients harboring EGFR rare mutation
Efficacy and prognosis comparison of first-line treatment with EGFR-TKI versus chemotherapy for non-small cell lung cancer patients harboring EGFR rare mutation
目的 探讨表皮生长因子受体（EGFR）少见突变非小细胞肺癌（NSCLC）患者一线接受EGFR酪氨酸激酶抑制剂（TKI）治疗与化疗的效果的差异。 方法 回顾性病例对照研究。回顾性收集2013年1月至2019年10月于山西省肿瘤医院接受治疗的伴EGFR少见突变的NSCLC患者资料。一线治疗前均采用扩增阻滞突变系统-聚合酶链反应（ARMS-PCR）检测活组织或血液EGFR突变情况。根据一线治疗方法将患者分为EGFR-TKI治疗组和化疗组。比较两组客观缓解率（ORR）、疾病控制率（DCR），采用Kaplan-Meier法绘制无进展生存（PFS）和总生存（OS）曲线，组间比较采用log-rank检验。采用单因素和多因素Cox比例风险模型分析PFS和OS的影响因素。 结果 169例EGFR少见突变患者纳入研究，年龄[M（IQR）]63岁（12岁），<65岁96例（56.8%），≥65岁73例（43.2%）；男性70例（41.4%），女性99例（58.6%）；EGFR G719X突变55例（32.5%），L861Q突变45例（26.6%），S768I突变17例（10.1%），复合突变52例（30.8%）；一线接受化疗55例（32.5%），一线接受EGFR-TKI治疗114例（67.5%）。化疗组患者ORR 36.4%（20/55），DCR 85.5%（47/55）；EGFR-TKI治疗组患者ORR 72.8%（83/114），DCR 90.4%（103/114）；EGFR-TKI治疗组ORR高于化疗组（χ2＝20.70，P＝0.001），DCR差异无统计学意义（χ2＝1.76，P＝0.184）。G719X、L861Q、复合突变的EGFR-TKI治疗组ORR均高于相应突变的化疗组，差异均有统计学意义（均P<0.05），但DCR差异均无统计学意义（均P>0.05）。EGFR-TKI治疗组中位PFS时间9.7个月（95%CI：6.0～13.4个月），化疗组中位PFS时间3.8个月（95%CI：3.1～7.1个月）；两组PFS差异有统计学意义（P<0.001）。EGFR-TKI治疗组中位OS时间25.6个月（95%CI：18.0～37.9个月），化疗组中位OS时间31.7个月（95%CI：18.0～42.8个月）；两组OS差异无统计学意义（P＝0.231）。多因素Cox回归分析显示，脑转移情况[有比无：HR＝2.306，95%CI：1.452～3.661，P<0.001]和一线治疗方式[EGFR-TKI治疗比化疗：HR＝0.457，95%CI：0.317～0.658，P<0.001]是EGFR少见突变NSCLC患者PFS的独立影响因素，脑转移情况（有比无：HR＝2.087，95%CI：1.102～3.953，P＝0.024；未知比无：HR＝2.118，95%CI：1.274～3.520，P＝0.004）为患者OS的独立影响因素。 结论 与一线化疗相比，一线EGFR-TKI治疗可改善EGFR少见突变NSCLC患者客观缓解及PFS，但未观察到OS获益。 Objective To investigate the therapeutic effect difference between first-line treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) and chemotherapy in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) rare mutation. Methods A retrospective case-control study was performed. Data of NSCLC patients with rare EGFR mutation who were treated in Shanxi Province Cancer Hospital from January 2013 to October 2019 were retrospectively analyzed. EGFR mutations in living tissues or blood were detected by using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) before first-line treatment. According to first-line treatment methods,they were divided into EGFR-TKI treatment group and chemotherapy group. Objective remission rate (ORR) and disease control rate (DCR) of both groups were compared. Kaplan-Meier method was used to draw progression-free survival (PFS) and the overall survival (OS) curves. Log-rank test was used for comparison among groups. Single-factor and multi-factor Cox proportional risk models were used to analyze the influencing factors of PFS and OS. Results A total of 169 patients with EGFR rare mutations were included, and the age [M (IQR)] was 63 years (12 years) there were 96 cases (56.8%) < 65 years and 73 cases (43.2%) ≥65 years 70 (41.4%)males and 99 (58.6%) females 55 cases (32.5%) had EGFR G719X mutation,45 cases (26.6%) had L861Q mutation, 17 cases (10.1%) had S768I mutation, and 52 cases (30.8%) had complex mutation 55 cases (32.5%) received the first-line chemotherapy and 114 cases (67.5%) received the first-line EGFR-TKI treatment. In the chemotherapy group, ORR was 36.4% (20/55) and DCR was 85.5% (47/55) in EGFR-TKI treatment group, ORR was 72.8% (83/114) and DCR was 90.4% (103/114). The ORR of EGFR-TKI treatment group was higher than that of chemotherapy group ( χ2 = 20.70, P = 0.001), and there was no statistically significant difference in DCR between two groups (χ2 = 1.76, P = 0.184). Subgroup analysis showed that ORR in EGFR-TKI treatment group with G719X, L861Q and complex mutations was higher than that of the corresponding mutations in chemotherapy group, and the differences were statistically significant (all P < 0.05), while there were no significant differences in DCR among subgroups (all P > 0.05). The median PFS time was 9.7 months (95% CI: 6.0-13.4 months) and 3.8 months (95% CI: 3.1-7.1 months), respectively in EGFR-TKI treatment group and chemotherapy group, and there was a statistically significant difference in PFS between the two groups (P < 0.001). The median OS time was 25.6 months (95% CI: 18.0-37.9 months) and 31.7 months (95% CI: 18.0-42.8 months), respectively in EGFR-TKI treatment group and chemotherapy group, and there was no statistically significant difference in OS between the two groups (P = 0.231). Multivariate Cox regression analysis showed that brain metastasis [with vs. without: HR = 2.306, 95% CI: 1.452-3.661, P < 0.001] and the first-line treatment methods (EGFR-TKI vs. chemotherapy: HR = 0.457, 95% CI:0.317-0.658, P < 0.001) were independent influencing factors for PFS of NSCLC patients with EGFR rare mutation brain metastasis (with vs. without: HR = 2.087, 95% CI: 1.102-3.953, P = 0.024 unknown vs. without: HR = 2.118,95% CI: 1.274-3.520, P = 0.004) were independent influencing factors for OS of NSCLC patients with EGFR rare mutation. Conclusions Compared with the first-line chemotherapy, EGFR-TKI first-line treatment could improve objective remission and PFS of NSCLC patients with EGFR rare mutation, while no OS benefit is observed.
Abstract
Objective To investigate the therapeutic effect difference between first-line treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) and chemotherapy in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) rare mutation. Methods A retrospective case-control study was performed. Data of NSCLC patients with rare EGFR mutation who were treated in Shanxi Province Cancer Hospital from January 2013 to October 2019 were retrospectively analyzed. EGFR mutations in living tissues or blood were detected by using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) before first-line treatment. According to first-line treatment methods,they were divided into EGFR-TKI treatment group and chemotherapy group. Objective remission rate (ORR) and disease control rate (DCR) of both groups were compared. Kaplan-Meier method was used to draw progression-free survival (PFS) and the overall survival (OS) curves. Log-rank test was used for comparison among groups. Single-factor and multi-factor Cox proportional risk models were used to analyze the influencing factors of PFS and OS. Results A total of 169 patients with EGFR rare mutations were included, and the age [M (IQR)] was 63 years (12 years) there were 96 cases (56.8%) < 65 years and 73 cases (43.2%) ≥65 years 70 (41.4%)males and 99 (58.6%) females 55 cases (32.5%) had EGFR G719X mutation,45 cases (26.6%) had L861Q mutation, 17 cases (10.1%) had S768I mutation, and 52 cases (30.8%) had complex mutation 55 cases (32.5%) received the first-line chemotherapy and 114 cases (67.5%) received the first-line EGFR-TKI treatment. In the chemotherapy group, ORR was 36.4% (20/55) and DCR was 85.5% (47/55) in EGFR-TKI treatment group, ORR was 72.8% (83/114) and DCR was 90.4% (103/114). The ORR of EGFR-TKI treatment group was higher than that of chemotherapy group ( χ2 = 20.70, P = 0.001), and there was no statistically significant difference in DCR between two groups (χ2 = 1.76, P = 0.184). Subgroup analysis showed that ORR in EGFR-TKI treatment group with G719X, L861Q and complex mutations was higher than that of the corresponding mutations in chemotherapy group, and the differences were statistically significant (all P < 0.05), while there were no significant differences in DCR among subgroups (all P > 0.05). The median PFS time was 9.7 months (95% CI: 6.0-13.4 months) and 3.8 months (95% CI: 3.1-7.1 months), respectively in EGFR-TKI treatment group and chemotherapy group, and there was a statistically significant difference in PFS between the two groups (P < 0.001). The median OS time was 25.6 months (95% CI: 18.0-37.9 months) and 31.7 months (95% CI: 18.0-42.8 months), respectively in EGFR-TKI treatment group and chemotherapy group, and there was no statistically significant difference in OS between the two groups (P = 0.231). Multivariate Cox regression analysis showed that brain metastasis [with vs. without: HR = 2.306, 95% CI: 1.452-3.661, P < 0.001] and the first-line treatment methods (EGFR-TKI vs. chemotherapy: HR = 0.457, 95% CI:0.317-0.658, P < 0.001) were independent influencing factors for PFS of NSCLC patients with EGFR rare mutation brain metastasis (with vs. without: HR = 2.087, 95% CI: 1.102-3.953, P = 0.024 unknown vs. without: HR = 2.118,95% CI: 1.274-3.520, P = 0.004) were independent influencing factors for OS of NSCLC patients with EGFR rare mutation. Conclusions Compared with the first-line chemotherapy, EGFR-TKI first-line treatment could improve objective remission and PFS of NSCLC patients with EGFR rare mutation, while no OS benefit is observed.
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