既往吉非替尼治疗获益的晚期NSCLC患者再次使用EGFR-TKI的选择:原药还是换药?

How to Make the Choice in the Retreatment of EGFR-TKI for Advanced NSCLC Patients Who Benefited from Prior Gefitinib Therapy: the Original Drug or Switching to A Second EGFR-TKI?

背景与目的既往表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinaseinhibitor,EGFR-TKI)治疗获益的晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者,再次给予TKI治疗,已逐渐成为一种新的治疗策略。本研究旨在探讨二次TKI治疗时,原药或换药,哪一种选择更为合理。方法回顾晚期或术后复发的NSCLC患者,既往吉非替尼治疗疗效达到完全缓解(complete response,CR)、部分缓解(partialresponse,PR)或稳定(stable disease,SD),无进展生存期(progression free survival,PFS)≥3个月,病情进展后,间隔时间至少1个月,分别接受吉非替尼或厄洛替尼治疗。就两组患者的疗效、优势人群等进行分析。结果共有61例患者入组,其中吉非替尼组30例,厄洛替尼组31例,两组患者基线特征基本平衡。吉非替尼组与厄洛替尼组疗效比较,有效率(response rate,RR)(10%vs 22.6%,P=0.300,6)、疾病控制率(disease contral rate,DCR)(60%vs 74.2%,P=0.237,8)、中位PFS(3.0个月vs 3.5个月,P=0.494,5)、中位总生存期(overall survival,OS)(8.3个月vs8.5个月,P=0.140,8)均未见统计学差异。多因素分析示:首次吉非替尼PFS≥6个月(HR=0.317,95%CI:0.102-0.984,P=0.046,9),两次TKI间隔时间≥3个月(HR=0.224,95%CI:0.071-0.713,P=0.011,3)的患者疾病进展风险降低。而两次TKI间隔时间≥3个月(HR=0.262,95%CI:0.097-0.705,P=0.008,0)的患者死亡风险降低。结论既往吉非替尼治疗获益的晚期NSCLC患者再次TKI治疗,无论选择吉非替尼还是换用厄洛替尼均可获益,这种获益与首次TKI的PFS、以及两次TKI的间隔时间相关。

Background and objective For advanced non-small cell lung cancer （NSCLC） patients who beneftted from prior epidermal growth factor receptor tyrosine kinase inhibitor （EGFR-TKI） therapy3 the choice of a second TKI therapy has gradually become a new strategy for the treatment. Some investigators recommend that the second therapy should be continued with the original TKI; however, other investigators recommend the administration of another TKI. The aim of this study is to explore which choice is more reasonable. Methods In retrospect, patients with advanced NSCLC or with postoperative relapse of advanced NSCLC achieved complete response （CR）, partial response （PR） or stable disease （SD） in prior Gefitinib therapy, progression free survival （PFS） 〉-3 months. They received repeated Gefitinib or Erlotinib at an interval of at least one month. The analysis was carried out with respect to efficacy and optimal population of the two groups. Results A total of 61 patients were enrolled into the study, 30 in Gefitinib group and 31 in Erlotinib group. Baseline characteristics of the two groups were comparable. In the comparison between patients treated with Gefitinib and with Erlotinib, no statistical differ- ences were seen for response rate （10% vs 22.6%, P=0.300,6）, disease control rate （60% vs 74.2%, P=0.237,8）, median PFS （3.0vs 3.5 months, P=0.494,5）, or median OS （8.3 vs 8.5 months, P=0.140,8）. Multivariate analysis showed that in the initial dose of Gefitinib, PFS-〉6 months （HR=0.317, 95%CI： 0.102-0.984, P=0.046,9）. With an interval _〉3 months （HR=0.224, 95%CI： 0.071-0.713, P=0.011,3） between two doses of TKI, the risk of disease progression was reduced; but if with an interval _〉3 months （HR=0.262, 95%CI： 0.097-0.705, P=0.008,0）, the risk of death was reduced. Conclusion Advanced NSCLC patients who benefited from prior Gefitinib therapy can benefit again either with the original drug Gefitinib or the alternative drug Erlotinib when a second TKI therapy is resumed. Such benefit is related to PFS of initial TKI therapy and time interval between two doses of TKI.