晚期肺癌奥西替尼获得性耐药进展模式及挽救治疗效果分析

目的探讨伴有表皮生长因子受体(EGFR)敏感突变或经酪氨酸激酶抑制剂(TKI)治疗后T790M突变的肺癌晚期患者接受奥西替尼治疗后的耐药进展模式以及挽救治疗方法和效果。方法收集2017年4月(奥西替尼在中国获批时)至2019年5月在江苏省肿瘤医院采用奥西替尼治疗的145例晚期肺癌患者资料。截至2019年12月最后一次随访,共87例(60.0%)患者发生奥西替尼获得性耐药,其中61例(70.1%)接受挽救治疗,对于耐药后爆发性进展者挽救治疗以化疗为主,对于耐药后缓慢进展或局部进展者,继续靶向药物治疗,并予局部治疗。采用影像学评价及Kaplan-Meier法分析奥西替尼获得性耐药的进展模式及生存情况,比较不同挽救治疗的效果。结果61例挽救性治疗患者中位随访11个月(4~32个月),其中58例(95.1%)出现了奥西替尼再次耐药,24例(39.3%)死于肺癌进展。61例挽救治疗患者的中位无进展生存(PFS)时间为2.5个月(95%CI 2.1~3.0个月);中位总生存(OS)时间为19.0个月(95%CI 13.7~26.3个月),1、2年OS率分别为72.1%和41.7%。61例挽救治疗患者中,爆发性进展、缓慢进展及局部进展分别为8例(13.1%)、30例(49.2%)及23例(37.7%)。在接受适当的挽救治疗后,爆发性进展、缓慢进展及局部进展患者间PFS及OS差异均无统计学意义(均P>0.05)。进展后接受局部治疗(24例)与未接受局部治疗(37例)患者间PFS及OS差异均无统计学意义(均P>0.05)。58例挽救治疗后再次耐药患者中仅6例(10.3%)在挽救治疗后获得超过6个月的PFS,均为缓慢进展或局部进展患者。结论奥西替尼获得性耐药在临床类型上可以表现为爆发性进展、缓慢进展及局部进展,挽救治疗效果欠佳。

Analyses of progression pattern of acquired resistance to osimertinib and the effect of salvage therapy in advanced lung cancer

Objective To investigate the progression pattern of acquired resistance to osimertinib and the treatment method as well as the therapeutic effect of salvage therapy in advanced lung cancer patients with epidermal growth factor receptor(EGFR)sensitive mutation or T790M mutation after the treatment of tyrosine-kinase inhibitor(TKI).Methods The data of 145 patients with advanced lung cancer treated with osimertinib in Jiangsu Cancer Hospital between April 2017(the approval time of osimertinib in China)and May 2019 were collected.At the last follow-up(December 2019),a total of 87(60.0%)patients had acquired resistance to osimertinib,61(70.1%)of whom received salvage treatment;for patients with dramatic progression after resistance,chemotherapy was mainly given in the salvage therapy;for patients with gradual or local progression after resistance,the continuing targeted drug therapy and the local therapy were given.Imaging evaluation and Kaplan-Meier method were used to analyze the progression pattern of acquired resistance to osimertinib and the survival status,and to compare the salvage treatment results among subgroups.Results The median follow-up time of 61 patients receiving salvage therapy was 11 months(4-32 months),among which 58(95.1%)patients again had resistance to osimertinib,and 24(39.3%)patients died of lung cancer.The median progression-free survival(PFS)time and overall survival(OS)time for the whole cohort was 2.5 months(95%CI 2.1-3.0 months)and 19.0 months(95%CI 13.7-26.3 months),respectively.The 1-year and 2-year OS rate was 72.1%and 41.7%,respectively.Among 61 patients receiving salvage therapy,8(13.1%),30(49.2%)and 23(37.7%)cases had dramatic progression,gradual progression and local progression,respectively;when given timely and proper salvage treatment,there were no statistically differences in PFS and OS of the patients in the above three subgroups(all P>0.05).There were no statistically differences in PFS and OS between patients receiving local therapy(24 cases)and patients not receiving local therapy(37 cases)after the progression occurred(all P>0.05).Among 58 patients with resistance to osimertinib again after the salvage therapy,6 patients with gradual or local progression had more than 6-mouth PFS after the salvage therapy.Conclusions Dramatic,gradual and local progression are the main patterns in patients with acquired resistance to osimertinib.The therapeutic efficacy of salvage therapy still shows some disappointing results.