目的:这项LASER201研究的一线队列分析评估了240mg拉泽尔替尼作为表皮生长因子受体(EGFR)突变的局部晚期或转移性非小细胞肺癌(NSCLC)的一线治疗的有效性和安全性。
方法:共43例患者,EGFR突变阳性(Exon19Del,n=24;L858R,n=18;G719X,n=1)先前未接受EGFR酪氨酸激酶抑制剂(EGFRTKI)治疗的局部晚期或转移性NSCLC,每天接受一次lazertinib240mg。通过局部或中央检测确认EGFR突变状态。主要终点是通过盲法独立中央审查评估的客观缓解率(ORR)。次要疗效终点包括反应持续时间(DoR),疾病控制率(DCR),无进展生存期(PFS),肿瘤缩小,总生存率(OS)。
结果:在主要数据截止日期(DCO;2021年1月8日),ORR为70%(95%置信区间[CI]:56.0-83.5),DCR为86%(95%CI:75.7-96.4),中位DoR为23.5(95%CI:12.5-未达到)个月。中位PFS为24.6个月(95%CI:12.2-30.2)。在最后的DCO(2023年3月30日),中位OS无法估计,中位OS随访时间为55.2个月[95%CI:22.8~55.7].36个月和54个月的OS率分别为66%(95%CI:47.5-79.3%)和55%(95%CI:36.6-70.7%),分别。最常报告的TEAE是皮疹(54%),腹泻(47%),瘙痒(35%),和感觉异常(35%)。没有报告3级或更高的药物相关皮疹或瘙痒TEAE。3例(7%)和1例(2%)患者报告了3级或更高的腹泻和感觉异常,分别。
结论:该分析表明,在以前未接受EGFRTKIs的EGFR突变的NSCLC患者中,使用lazertinib240mg可长期临床获益。拉泽替尼的安全性是可耐受的,与以前报道的一致。
OBJECTIVE: This analysis of the first-line cohort of LASER201 study evaluated the efficacy and safety of
lazertinib 240 mg as a frontline therapy for epidermal growth factor receptor (EGFR)-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC).
METHODS: A total of 43 patients, with EGFR mutation-positive (Exon19Del, n = 24; L858R, n = 18; G719X, n = 1) locally advanced or metastatic NSCLC who had not previously received EGFR tyrosine kinase inhibitor (EGFR TKI) therapy, received once-daily
lazertinib 240 mg. EGFR mutation status was confirmed by local or central testing. The primary endpoint was objective response rate (ORR) assessed by blinded independent central review. Secondary efficacy endpoints included duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), tumor shrinkage, and overall survival (OS).
RESULTS: At the primary data cut-off (DCO; January 8, 2021), the ORR was 70 % (95 % confidence interval [CI]: 56.0-83.5), DCR was 86 % (95 % CI: 75.7-96.4) and the median DoR was 23.5 (95 % CI: 12.5-not reached) months. The median PFS was 24.6 (95 % CI: 12.2-30.2) months. At the final DCO (March 30, 2023), the median OS was not estimable and the median follow-up duration for OS was 55.2 [95 % CI: 22.8-55.7] months. OS rates at 36 months and 54 months were 66 % (95 % CI: 47.5-79.3 %) and 55 % (95 % CI: 36.6-70.7 %), respectively. The most commonly reported TEAEs were rash (54 %), diarrhea (47 %), pruritus (35 %), and paresthesia (35 %). No drug-related rash or pruritus TEAEs of grade 3 or higher were reported. Diarrhea and paresthesia of grade 3 or higher were reported in 3 (7 %) and 1 (2 %) patients, respectively.
CONCLUSIONS: This analysis demonstrated long-term clinical benefit with
lazertinib 240 mg in patients with EGFR-mutated NSCLC who had not previously received EGFR TKIs. The safety profile for
lazertinib was tolerable and consistent with that previously reported.