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Abstract：
BACKGROUND: Lazertinib is a third-generation tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR-TKI) that selectively inhibit common EGFR mutation and T790M mutation in non-small-cell lung cancer (NSCLC) patients. No previous studies have compared lazertinib to platinum-based chemotherapy. We have compared lazertinib with platinum-based chemotherapy in EGFR-mutated NSCLC patients after previous EGFR-TKI therapy.
METHODS: We retrospectively compared 200 patients from LASER201, LASER301, and LASER-PMS studies to 334 patients who were treated with platinum-based chemotherapy after previous EGFR-TKI from the Samsung Medical Center. After propensity score matching (PSM), we selected 156 patients from each group. The primary outcome was progression-free survival (PFS), with overall survival (OS), objective response rate (ORR), and time to treatment discontinuation (TTD) as secondary outcomes.
RESULTS: The median follow-up of PFS was 15.61 months in the lazertinib group and 21.67 months in the external control group. The PFS was significantly longer in patients who were treated with lazertinib than those treated with platinum-based chemotherapy (10.97 months vs. 5.10 months; adjusted hazard ratio (HR) 0.40; 95% confidence interval (CI), 0.29-0.55; p < 0.01) after PSM. Lazertinib showed superior OS (32.23 months vs. 18.73 months; adjusted HR 0.45; 95% CI, 0.29-0.69; p < 0.001), ORR (64.1% vs. 47.4%), and TTD (11.66 months vs. 6.73 months; adjusted HR 0.54; 95% CI, 0.39-0.75; p < 0.001) compared to platinum-based chemotherapy.
CONCLUSIONS: Based on this retrospective, external control study, lazertinib has demonstrated significantly better efficacy compared with platinum-based chemotherapy. The external controls provide important context to evaluate efficacy in single-arm studies.
METHODS: We retrospectively compared 200 patients from LASER201, LASER301, and LASER-PMS studies to 334 patients who were treated with platinum-based chemotherapy after previous EGFR-TKI from the Samsung Medical Center. After propensity score matching (PSM), we selected 156 patients from each group. The primary outcome was progression-free survival (PFS), with overall survival (OS), objective response rate (ORR), and time to treatment discontinuation (TTD) as secondary outcomes.
RESULTS: The median follow-up of PFS was 15.61 months in the lazertinib group and 21.67 months in the external control group. The PFS was significantly longer in patients who were treated with lazertinib than those treated with platinum-based chemotherapy (10.97 months vs. 5.10 months; adjusted hazard ratio (HR) 0.40; 95% confidence interval (CI), 0.29-0.55; p < 0.01) after PSM. Lazertinib showed superior OS (32.23 months vs. 18.73 months; adjusted HR 0.45; 95% CI, 0.29-0.69; p < 0.001), ORR (64.1% vs. 47.4%), and TTD (11.66 months vs. 6.73 months; adjusted HR 0.54; 95% CI, 0.39-0.75; p < 0.001) compared to platinum-based chemotherapy.
CONCLUSIONS: Based on this retrospective, external control study, lazertinib has demonstrated significantly better efficacy compared with platinum-based chemotherapy. The external controls provide important context to evaluate efficacy in single-arm studies.
摘要：
背景：拉泽替尼是第三代表皮生长因子受体（EGFR-TKI）酪氨酸激酶抑制剂，可选择性抑制非小细胞肺癌（NSCLC）患者的常见EGFR突变和T790M突变。以前没有研究将拉泽替尼与铂类化疗进行比较。我们比较了之前EGFR-TKI治疗后EGFR突变的NSCLC患者的拉泽替尼和铂类化疗。
方法：我们回顾性比较了来自LASER201、LASER301和LASER-PMS研究的200例患者与三星医学中心先前EGFR-TKI后接受铂类化疗的334例患者。在倾向得分匹配(PSM)之后，我们从每组中选择了156例患者.主要结果是无进展生存期（PFS），总生存率（OS），客观反应率（ORR），和治疗终止时间（TTD）作为次要结局。
结果：拉泽替尼组的PFS中位随访时间为15.61个月，外部对照组为21.67个月。与使用铂类化疗治疗的患者相比，使用拉泽替尼治疗的患者的PFS明显更长（10.97个月与5.10个月；调整风险比（HR）0.40；95%置信区间（CI），0.29-0.55；p<0.01）PSM后。拉泽替尼显示出优异的OS（32.23个月与18.73个月；调整后的HR0.45；95%CI，0.29-0.69；p<0.001），ORR（64.1%vs.47.4%），和TTD（11.66个月vs.6.73个月；与铂类化疗相比，调整后的HR0.54；95%CI，0.39-0.75；p<0.001）。
结论：基于此回顾性研究，外部控制研究，与以铂类为基础的化疗相比,拉泽替尼显示出显著更好的疗效.外部对照为评估单臂研究的疗效提供了重要的背景。
方法：我们回顾性比较了来自LASER201、LASER301和LASER-PMS研究的200例患者与三星医学中心先前EGFR-TKI后接受铂类化疗的334例患者。在倾向得分匹配(PSM)之后，我们从每组中选择了156例患者.主要结果是无进展生存期（PFS），总生存率（OS），客观反应率（ORR），和治疗终止时间（TTD）作为次要结局。
结果：拉泽替尼组的PFS中位随访时间为15.61个月，外部对照组为21.67个月。与使用铂类化疗治疗的患者相比，使用拉泽替尼治疗的患者的PFS明显更长（10.97个月与5.10个月；调整风险比（HR）0.40；95%置信区间（CI），0.29-0.55；p<0.01）PSM后。拉泽替尼显示出优异的OS（32.23个月与18.73个月；调整后的HR0.45；95%CI，0.29-0.69；p<0.001），ORR（64.1%vs.47.4%），和TTD（11.66个月vs.6.73个月；与铂类化疗相比，调整后的HR0.54；95%CI，0.39-0.75；p<0.001）。
结论：基于此回顾性研究，外部控制研究，与以铂类为基础的化疗相比,拉泽替尼显示出显著更好的疗效.外部对照为评估单臂研究的疗效提供了重要的背景。
