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  • Title: [Efficacy of chemotherapy after EGFR-TKIs resistance in 191 patients with Unknow EGFR gene mutation in advanced lung adenocarcinoma].
    Author: He P, Wang Y, Yang S, Yu S, Wang Z, Li J, Wang B, Hao X, Wang H, Hu X, Zhang X, Shi Y.
    Journal: Zhongguo Fei Ai Za Zhi; 2013 Oct 20; 16(10):529-34. PubMed ID: 24113006.
    Abstract:
    BACKGROUND AND OBJECTIVE: Subsequent chemotherapy were needed in patients with advanced pulmonary adenocarcinoma experiencing disease progression after epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment. The study is to explore factors potentially influencing efficacy of subsequent chemotherapy. METHODS: 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: The 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 obvisous [objective response rate (ORR) 14.3% vs 3.7%, P=0.041]. The 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). The patients treated with platinum-based chemotherapy had longer PFS and OS than those with non-platinum-based chemotherapy, 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 benefits from platinum-based chemotherapy. However there was no significant difference in ORR, PFS or OS between patients with TKIs primary resistance and acquired resistance, or between dramtic progression and gradual/local progression. CONCLUSION: The patients with advanced lung adenocarcinoma might get benefits from pemetrexed-based or platinum-based chemotherapy after they were EGFR-TKIs resistace. 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。
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