Kim Kibum, Syeed Sakil, Au Trang, Diaz Amber, Schabath Matthew B, Cass Amanda, Hall Richard, Pai Lori, Li Chenghui, Balmaceda Nicole, Palumbo Alison, Carey Autumn, Lalla Mumtu, Henry Matthew, Brixner Diana, Stenehjem David
University of Utah, Department of Pharmacotherapy and Pharmacotherapy Outcomes Research Center, Salt Lake City, UT, USA; University of Illinois Chicago, Department of Pharmacy Systems, Outcomes and Policy, Chicago, IL, USA.
University of Utah, Department of Pharmacotherapy and Pharmacotherapy Outcomes Research Center, Salt Lake City, UT, USA.
Cancer Treat Res Commun. 2025;43:100898. doi: 10.1016/j.ctarc.2025.100898. Epub 2025 Mar 13.
Osimertinib is a third-generation EGFR-TKI and preferred first-line (1L) treatment for EGFR positive (EGFR+) metastatic non-small cell lung cancer (mNSCLC). This study compared real-world clinical outcomes of 1L osimertinib versus 1st or 2nd generation EGFR-TKIs (1/2G-TKIs) in patients with EGFR+ mNSCLC.
Nine academic cancer centers in the US participated in the retrospective cohort study. Patients aged ≥18 years with EGFR+ mNSCLC and treated with 1L EGFR-TKI were included. Clinical outcomes included real-world progression-free survival (rwPFS), duration of treatment (DOT), time to next treatment (TTNT), central nervous system incidence-free survival (CNS-IFS), and overall survival (OS). Multivariable regression models were used to control for differences in patient characteristics (p < 0.1) between the osimertinib and 1/2G-TKI cohorts.
The study included 181 osimertinib patients and 171 1/2G-TKI patients. Osimertinib had a longer rwPFS compared to 1/2G-TKIs (median PFS, 95 % confidence interval [CI]: 16.2 months (13.2-19.7) vs. 10.8 months (9.5-12.7); hazard Ratio [HR], 95 % CI: 0.60 (0.44-0.82). DOT and TTNT were significantly longer in patients treated with osimertinib versus 1/2G-TKI (HR, 95 % CI: 0.51 (0.38-0.68) for DOT; 0.54 (0.39-0.74) for TTNT). The respective HR point estimate for CNF-IFS and OS of 0.62 and 0.83 preferred osimertinib. However, small patient counts and number of events posed challenges in drawing conclusion regarding the significance of the delayed CNS-IFS or OS.
Patients treated with osimertinib had a prolonged time to progression and longer time maintain the treatment compared to 1/2G-TKI. This real-world evidence is aligned with clinical trial results.
奥希替尼是第三代表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI），是表皮生长因子受体阳性（EGFR+）转移性非小细胞肺癌（mNSCLC）一线治疗的首选药物。本研究比较了EGFR+ mNSCLC患者中一线使用奥希替尼与第一代或第二代EGFR-TKI（1/2G-TKI）的真实世界临床疗效。
美国9个学术癌症中心参与了这项回顾性队列研究。纳入年龄≥18岁、接受一线EGFR-TKI治疗的EGFR+ mNSCLC患者。临床疗效包括真实世界无进展生存期（rwPFS）、治疗持续时间（DOT）、下次治疗时间（TTNT）、中枢神经系统无事件生存期（CNS-IFS）和总生存期（OS）。采用多变量回归模型控制奥希替尼组和1/2G-TKI组患者特征的差异（p<0.1）。
该研究纳入了181例使用奥希替尼的患者和171例使用1/2G-TKI的患者。与1/2G-TKI相比，奥希替尼的rwPFS更长（中位PFS，95%置信区间[CI]：16.2个月（13.2 - 19.7）对10.8个月（9.5 - 12.7）；风险比[HR]，95%CI：0.60（0.44 - 0.82））。与1/2G-TKI相比，使用奥希替尼治疗的患者DOT和TTNT显著更长（DOT的HR，95%CI：0.51（0.38 - 0.68）；TTNT的HR，95%CI：0.54（0.39 - 0.74））。CNF-IFS和OS的HR点估计值分别为0.62和0.83，表明奥希替尼更具优势。然而，患者数量少和事件数量在就延迟的CNS-IFS或OS的显著性得出结论方面带来了挑战。
与1/2G-TKI相比，使用奥希替尼治疗的患者疾病进展时间延长，治疗维持时间更长。这一真实世界证据与临床试验结果一致。
