背景:在HER2阳性的晚期非小细胞肺癌(NSCLC)患者中,阿法替尼或吡罗替尼的疗效已得到证实;然而,阿法替尼进展后使用吡唑替尼的疗效尚待确定.
方法:纳入接受阿法替尼或吡唑替尼单药治疗的HER2突变的晚期肺腺癌患者。进一步分析在阿法替尼后接受吡唑替尼的患者,以确定阿法替尼进展后吡唑替尼的疗效和安全性。用Kaplan-Meier方法绘制存活曲线。使用游泳图来描述具体的治疗方法。此外,从HER2扩增的NSCLC患者样本中建立患者来源的肿瘤类器官(PDTOs),以研究吡罗替尼在HER2扩增的肿瘤细胞中的体外抗肿瘤活性.
结果:共纳入99例患者,其中13人在阿法替尼进展后给予吡唑替尼。是否在阿法替尼进展后治疗的患者之间观察到吡唑替尼的PFS无统计学差异(6.7个月与4.4个月,P=0.817),因此表明阿法替尼的进展并不影响吡唑替尼的疗效.对以前的患者进行了进一步分析,其中包括8例患者在阿法替尼进展后接受间隔化疗。两名患者在接受吡唑替尼治疗后获得PR。未发现影响pyrotinibPFS的独立因素。PDTOs证实了吡罗替尼在HER2扩增的NSCLC肿瘤细胞中的抗肿瘤活性。
结论:先前阿法替尼治疗后进展不影响吡罗替尼治疗的疗效。对于使用阿法替尼经历进展的HER2突变患者,吡柔替尼可能是一种挽救选择。
BACKGROUND: The efficacy of
afatinib or pyrotinib has been demonstrated in HER2-positive advanced non-small cell lung cancer (NSCLC) patients; however, the efficacy of pyrotinib after
afatinib progression has yet to be determined.
METHODS: Patients with HER2 mutated advanced lung adenocarcinoma administered
afatinib or pyrotinib monotherapy were enrolled. Those who received pyrotinib after
afatinib were further analyzed to determine the efficacy and safety of pyrotinib after progression on
afatinib. Survival curves were plotted with the Kaplan-Meier method. A swimming plot was used to describe the specific treatments. Additionally, patient-derived tumor organoids (PDTOs) were established from HER2-amplified NSCLC patient samples to investigate the antitumor activity of pyrotinib in HER2-amplified tumor cells in vitro.
RESULTS: A total of 99 patients were enrolled, 13 of whom were administered pyrotinib after progression on afatinib. No statistical difference in PFS of pyrotinib was observed between patients whether be treated after afatinib progression or not (6.7 months vs. 4.4 months, P = 0.817), thus indicating that progression on afatinib did not affect the efficacy of pyrotinib. Further analysis was conducted on the former patients, which comprising eight patients administered interval chemotherapy after progression on afatinib. Two patients achieved PR after pyrotinib treatment. No independent factors were found to influence the PFS of pyrotinib. PDTOs confirmed the anti-tumor activity of pyrotinib in NSCLC tumor cells with HER2 amplification.
CONCLUSIONS: Progression after prior afatinib treatment does not influence the efficacy of pyrotinib treatment. Pyrotinib may be a salvage option for patients with HER2 mutation who have experienced progression on afatinib.