表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）治疗失败后接受铂类-培美曲塞治疗的晚期EGFR突变型非小细胞肺癌患者生存结局的真实世界分析
Real-world analysis of survival outcomes in advanced EGFR-mutant NSCLC patients treated with platinum-pemetrexed after EGFR-TKI treatment failure.
作者信息
Yao Zong-Han, Liao Wei-Yu, Yang Chin-Yao, Ho Chao-Chi, Shih Jin-Yuan, Chen Kuan-Yu, Yang James Chih-Hsin, Yu Chong-Jen
机构信息
Department of Internal Medicine, National Taiwan University Cancer Center and National Taiwan University College of Medicine, Taipei, Taiwan; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
出版信息
J Formos Med Assoc. 2024 Aug 15. doi: 10.1016/j.jfma.2024.08.017.
INTRODUCTION
EGFR tyrosine kinase inhibitors (TKIs) are the standard therapy for non-small-cell lung cancer (NSCLC) patients with EGFR-activating mutations in the first-line setting. Despite initial efficacy, resistance to EGFR-TKIs often develops, and platinum-based chemotherapy is the predominant subsequent treatment. For this study, we aimed to identify prognostic factors for overall survival (OS) and progression-free survival (PFS) among advanced EGFR-mutant NSCLC patients receiving platinum-pemetrexed after progression on EGFR-TKIs. Our analysis specifically focuses on 1st-line treatments limited to 1st- or 2nd-generation EGFR-TKIs, while not restricting later-line treatments involving osimertinib prior to chemotherapy.
MATERIALS AND METHODS
From 2012 to 2017, 363 patients who received first-line treatment with first- or second-generation EGFR-TKIs, including gefitinib, erlotinib, and afatinib were enrolled. Some patients received different EGFR-TKIs, including osimertinib, as later-line treatment before platinum-pemetrexed.
RESULTS
Median OS from the initiation of platinum-pemetrexed was 22.0 months and median PFS with platinum-pemetrexed was 6.2 months. In the multivariate Cox model, we identified three independent prognostic factors for better OS: postoperative recurrence (HR: 0.34, p = 0.004), first-line EGFR-TKI PFS ≥12 months (HR: 0.54, p = 0.002), and osimertinib treatment after platinum-pemetrexed (HR: 0.56, p = 0.005) while BMI <18.5 indicated poor prognosis (HR:1.76, p = 0.049). No statistically significant independent prognostic factors for PFS were found. Receiving osimertinib before platinum-pemetrexed treatment did not impact PFS with platinum-pemetrexed treatment (HR: 1.11, p = 0.64).
CONCLUSION
Postoperative recurrence, first-line EGFR-TKI PFS ≥12 months and osimertinib treatment after platinum-pemetrexed predicted better OS, while BMI <18.5 predicted worse OS. Osimertinib treatment before platinum-pemetrexed treatment did not affect the efficacy of platinum-pemetrexed.
引言
表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）是一线治疗中表皮生长因子受体（EGFR）激活突变的非小细胞肺癌（NSCLC）患者的标准疗法。尽管初始疗效显著，但对EGFR-TKIs的耐药性通常会出现，铂类化疗是后续的主要治疗方法。在本研究中，我们旨在确定在接受EGFR-TKIs治疗进展后接受铂类培美曲塞治疗的晚期EGFR突变NSCLC患者中总生存期（OS）和无进展生存期（PFS）的预后因素。我们的分析特别关注仅限于第一代或第二代EGFR-TKIs的一线治疗，而不限制化疗前使用奥希替尼的后续治疗。
材料与方法
2012年至2017年，纳入363例接受第一代或第二代EGFR-TKIs一线治疗的患者，包括吉非替尼、厄洛替尼和阿法替尼。一些患者在铂类培美曲塞治疗前接受了不同的EGFR-TKIs，包括奥希替尼作为后续治疗。
结果
从开始铂类培美曲塞治疗起的中位OS为22.0个月，铂类培美曲塞治疗的中位PFS为6.2个月。在多变量Cox模型中，我们确定了三个与更好的OS相关的独立预后因素：术后复发（HR：0.34，p = 0.004）、一线EGFR-TKI PFS≥12个月（HR：0.54，p = 0.002）以及铂类培美曲塞治疗后使用奥希替尼（HR：0.56，p = 0.005），而BMI<18.5表明预后较差（HR：1.76，p = 0.049）。未发现PFS有统计学意义的独立预后因素。在铂类培美曲塞治疗前接受奥希替尼治疗并不影响铂类培美曲塞治疗的PFS（HR：1.11，p = 0.64）。
结论
术后复发、一线EGFR-TKI PFS≥12个月以及铂类培美曲塞治疗后使用奥希替尼预示着更好的OS，而BMI<18.5预示着更差的OS。在铂类培美曲塞治疗前使用奥希替尼治疗不影响铂类培美曲塞的疗效。
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