Addeo Alfredo, Hochmair Maximilian, Janzic Urska, Dudnik Elizabeth, Charpidou Andriani, Płużański Adam, Ciuleanu Tudor, Donev Ivan Shterev, Elbaz Judith, Aarøe Jørgen, Ott René, Peled Nir
Medical Oncology, Geneva University Hospital, Geneva, Switzerland.
Department of Respiratory and Critical Care Medicine, Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Klinik Floridsdorf, Brünner Strasse 68, A-1210 Vienna, Austria.
Ther Adv Med Oncol. 2021 Nov 29;13:17588359211059874. doi: 10.1177/17588359211059874. eCollection 2021.
For epidermal growth factor receptor mutation-positive (EGFRm) non-small-cell lung cancer (NSCLC), EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are the preferred first-line (1 L) treatment in the advanced setting. Osimertinib, a third-generation EGFR-TKI, received full approval in 2017 for second-line (2 L) treatment of EGFR T790M-positive NSCLC. The REFLECT study characterizes real-world treatment/testing patterns, attrition rates, and outcomes in patients with EGFRm advanced NSCLC treated with 1 L first-/second-generation (1G/2G) EGFR-TKIs before 1 L osimertinib approval.
Retrospective chart review (NCT04031898) of European/Israeli adults with EGFRm unresectable locally advanced/metastatic NSCLC, initiating 1 L 1G/2G EGFR-TKIs 01/01/15-30/06/18 (index date).
In 896 patients (median follow-up of 21.5 months), the most frequently initiated 1 L EGFR-TKI was afatinib (45%). Disease progression was reported in 81%, including 10% (86/896) who died at 1 L. By the end of study, most patients discontinued 1 L (85%), of whom 33% did not receive 2 L therapy. From index, median 1 L real-world progression-free survival was 13.0 (95% confidence interval (CI): 12.3-14.1) months; median overall survival (OS) was 26.2 (95% CI: 23.6-28.4) months. 71% of patients with 1 L progression were tested for T790M; 58% were positive. Of those with T790M, 95% received osimertinib in 2 L or later. Central nervous system (CNS) metastases were recorded in 22% at index, and 15% developed CNS metastases during treatment (median time from index 13.5 months). Median OS was 19.4 months (95% CI: 17.1-22.1) in patients with CNS metastases at index, 24.8 months (95% CIs not available) with CNS metastases diagnosed during treatment, and 30.3 months (95% CI: 27.1, 33.8) with no CNS metastases recorded.
REFLECT is a large real-world study describing treatment patterns prior to 1 L osimertinib availability for EGFRm advanced NSCLC. Given the attrition rates highlighted in the study and the impact of CNS progression on outcomes, offering a 1 L EGFR-TKI with CNS penetration may improve patient outcomes in this treatment setting.
对于表皮生长因子受体突变阳性（EGFRm）的非小细胞肺癌（NSCLC），EGFR酪氨酸激酶抑制剂（EGFR-TKIs）是晚期患者首选的一线治疗方法。奥希替尼是第三代EGFR-TKI，于2017年获得全面批准，用于EGFR T790M阳性NSCLC的二线治疗。REFLECT研究描述了在奥希替尼获批用于一线治疗之前，接受一线第一代/第二代（1G/2G）EGFR-TKIs治疗的EGFRm晚期NSCLC患者的真实世界治疗/检测模式、损耗率和治疗结果。
对欧洲/以色列患有EGFRm不可切除的局部晚期/转移性NSCLC的成年人进行回顾性图表审查（NCT04031898），这些患者于2015年1月1日至2018年6月30日开始接受一线1G/2G EGFR-TKIs治疗（索引日期）。
在896例患者中（中位随访21.5个月），最常开始使用的一线EGFR-TKI是阿法替尼（45%）。81%的患者报告疾病进展，其中10%（86/896）在一线治疗时死亡。到研究结束时，大多数患者停止了一线治疗（85%），其中33%未接受二线治疗。从索引日期开始，一线真实世界的无进展生存期中位数为13.0（95%置信区间（CI）：12.3-14.1）个月；中位总生存期（OS）为26.2（95%CI：23.6-28.4）个月。71%一线治疗进展的患者接受了T790M检测；58%为阳性。在那些T790M阳性的患者中，95%在二线或更晚接受了奥希替尼治疗。索引日期时22%的患者有中枢神经系统（CNS）转移，治疗期间15%的患者出现CNS转移（从索引日期起的中位时间为13.5个月）。索引日期时有CNS转移的患者中位OS为19.4个月（95%CI：17.1-22.1），治疗期间诊断出有CNS转移的患者中位OS为24.8个月（95%CI未提供），未记录有CNS转移的患者中位OS为30.3个月（95%CI：27.1,33.8）。
REFLECT是一项大型真实世界研究，描述了在奥希替尼可用于EGFRm晚期NSCLC一线治疗之前的治疗模式。鉴于该研究中突出的损耗率以及CNS进展对治疗结果的影响，提供一种具有CNS穿透性的一线EGFR-TKI可能会改善这种治疗环境下患者的治疗结果。
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