Department of Haematology-Oncology, National University Cancer Institute, Singapore.
Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
J Thorac Oncol. 2023 Dec;18(12):1756-1766. doi: 10.1016/j.jtho.2023.08.017. Epub 2023 Oct 22.
Lazertinib, a third-generation mutant-selective EGFR tyrosine kinase inhibitor, improved progression-free survival compared with gefitinib in the phase 3 LASER301 study (ClinicalTrials.gov Identifier: NCT04248829). Here, we report the efficacy of lazertinib and gefitinib in patients with baseline central nervous system (CNS) metastases.
Treatment-naive patients with EGFR-mutated advanced NSCLC were randomized one-to-one to lazertinib (240 mg/d) or gefitinib (250 mg/d). Patients with asymptomatic or stable CNS metastases were included if any planned radiation, surgery, or steroids were completed more than 2 weeks before randomization. For patients with CNS metastases confirmed at screening or subsequently suspected, CNS imaging was performed every 6 weeks for 18 months, then every 12 weeks. End points assessed by blinded independent central review and Response Evaluation Criteria in Solid Tumors version 1.1 included intracranial progression-free survival, intracranial objective response rate, and intracranial duration of response.
Of the 393 patients enrolled in LASER301, 86 (lazertinib, n = 45; gefitinib, n = 41) had measurable and or non-measurable baseline CNS metastases. The median intracranial progression-free survival in the lazertinib group was 28.2 months (95% confidence interval [CI]: 14.8-28.2) versus 8.4 months (95% CI: 6.7-not reached [NR]) in the gefitinib group (hazard ratio = 0.42, 95% CI: 0.20-0.89, p = 0.02). Among patients with measurable CNS lesions, the intracranial objective response rate was numerically higher with lazertinib (94%; n = 17) versus gefitinib (73%; n = 11, p = 0.124). The median intracranial duration of response with lazertinib was NR (8.3-NR) versus 6.3 months (2.8-NR) with gefitinib. Tolerability was similar to the overall LASER301 population.
In patients with CNS metastases, lazertinib significantly improved intracranial progression-free survival compared with gefitinib, with more durable responses.
拉泽替尼是一种第三代突变选择性 EGFR 酪氨酸激酶抑制剂，与 gefitinib 相比，在 III 期 LASER301 研究中改善了无进展生存期（ClinicalTrials.gov 标识符：NCT04248829）。在这里，我们报告拉泽替尼和 gefitinib 在基线有中枢神经系统（CNS）转移的患者中的疗效。
未经治疗的 EGFR 突变型晚期 NSCLC 患者被随机分为一组，接受拉泽替尼（240 mg/d）或 gefitinib（250 mg/d）治疗。如果任何计划的放疗、手术或类固醇治疗在随机分组前超过 2 周完成，则无症状或稳定的 CNS 转移患者也被纳入。对于在筛选时或随后怀疑有 CNS 转移的患者，在 18 个月内每 6 周进行一次 CNS 成像，然后每 12 周进行一次。通过盲法独立中心审查和实体瘤反应评估标准 1.1 评估的终点包括颅内无进展生存期、颅内客观缓解率和颅内缓解持续时间。
在 LASER301 中入组的 393 例患者中，有 86 例（拉泽替尼组，n=45；吉非替尼组，n=41）有可测量和/或不可测量的基线 CNS 转移。拉泽替尼组的中位颅内无进展生存期为 28.2 个月（95%置信区间：14.8-28.2），吉非替尼组为 8.4 个月（95%置信区间：6.7-NR）（风险比=0.42，95%置信区间：0.20-0.89，p=0.02）。在有可测量的 CNS 病变的患者中，拉泽替尼的颅内客观缓解率（94%；n=17）高于吉非替尼（73%；n=11，p=0.124）。拉泽替尼的中位颅内缓解持续时间为 NR（8.3-NR），吉非替尼为 6.3 个月（2.8-NR）。耐受性与 LASER301 总体人群相似。
在有 CNS 转移的患者中，与 gefitinib 相比，拉泽替尼显著改善了颅内无进展生存期，且缓解更持久。
