191例EGFR突变状态不明晚期肺腺癌患者EGFR-TKIs耐药后化疗的疗效分析

摘要

背景与目的晚期肺腺癌患者在使用表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor tyrosine kinase inhibitors, EGFR-TKIs）治疗进展后需要接受化疗。本研究旨在探讨EGFR-TKIs耐药后进行化疗的疗效影响因素。方法回顾性分析191例晚期肺腺癌患者的临床特征、EGFR-TKIs耐药后第一次化疗的近期疗效及生存时间。结果含培美曲塞方案的有效率明显高于不含培美曲塞组，客观缓解率（objective response rate, ORR）分别为9.3%和1.1%（P=0.011），以二线化疗更为明显，ORR分别为14.3%和3.7%（P=0.041）。化疗最好疗效达部分缓解（partial response, PR）者的无进展生存期（progression-free survival, PFS）明显长于未达到PR者（PFS分别为10.1个月和2.3个月，P=0.012）；含铂方案的PFS及总生存期（overall survival, OS）均长于不含铂方案，是独立的预后因素[PFS：相对风险（relative risk, RR）=0.634，95%CI：0.466-0.832，P=0.004；OS：RR=0.666，95%CI：0.460-0.960， P=0.030]，其中TKIs获得性耐药的患者和爆发式进展的患者进行含铂化疗生存获益更多。TKIs耐药的性质（原发或获得性）及TKIs耐药模式（爆发进展、缓慢进展和局部进展）对后续化疗的ORR、PFS及OS均无明显影响。结论对于EGFR-TKIs耐药的晚期肺腺癌患者，含培美曲塞方案和含铂方案可能疗效较好。%Background and objective Subsequent chemotherapy were needed in patients with advanced pul-monary adenocarcinoma experiencing disease progression atfer epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment. hTe study is to explore factors potentially inlfuencing effcacy of subsequent chemotherapy. Meth-ods One hundred and ninety-one patients with advanced lung adenocarcinoma, who were resistant from EGFR-TKIs and then received subsequent chemotherapy, were identified. Data of patient’s characteristics, responses to chemotherapy and survival time were analyzed retrospectively. Results hTe overall response rate of the pemetrexed-based chemotherapy (9.3%) was higher than non-pemetrexed-based regimen (1.1%), P=0.011. Furthermore, the response in the second-line was more ob-visous [objective response rate (ORR) 14.3%vs 3.7%, P=0.041]. hTe patients who achieved response of partial response (PR) showed longer progression-free survival (PFS) than those who achieved non-PR (PFS 10.1 months and 2.3 months, P=0.012). hTe patients treated with platinum-based chemotherapy had longer PFS and OS than those with non-platinum-based che-motherapy, therefore platinum-based regimen was independent prognosis factors for PFS and OS (PFS:RR=0.634, 95%CI:0.466-0.832, P=0.004;OS:RR=0.666, 95%CI:0.460-0.960, P=0.030), especially the pateients who were aquired EGFR-TKIs resistance and who got drmatic progression from EGFR-TKIs treatment might got more beneifts from platinum-based chemo-therapy. However there was no signiifcant difference in ORR, PFS or OS between patients with TKIs primary resistance and acquired resistance, or between dramtic progression and gradual/local progression. Conclusion hTe patients with advanced lung adenocarcinoma might get beneifts from pemetrexed-based or platinum-based chemotherapy atfer they were EGFR-TKIs resistace.