The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310000, China.
Department of Clinical Trial, Zhejiang Cancer Hospital, No.1 East Banshan Road, Gongshu District, Hangzhou, 310022, Zhejiang, China.
Clin Transl Oncol. 2024 Dec;26(12):3050-3057. doi: 10.1007/s12094-024-03482-9. Epub 2024 May 25.
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.
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.
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.
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.
阿法替尼或吡咯替尼已被证实对 HER2 阳性晚期非小细胞肺癌（NSCLC）患者有效；然而，阿法替尼进展后使用吡咯替尼的疗效尚不确定。
入组接受阿法替尼或吡咯替尼单药治疗的 HER2 突变晚期肺腺癌患者。对接受阿法替尼后使用吡咯替尼的患者进行进一步分析，以确定阿法替尼进展后使用吡咯替尼的疗效和安全性。采用 Kaplan-Meier 法绘制生存曲线。采用泳道图描述具体治疗情况。此外，从 HER2 扩增 NSCLC 患者样本中建立患者来源的肿瘤类器官（PDTO），以研究吡咯替尼在体外对 HER2 扩增肿瘤细胞的抗肿瘤活性。
共入组 99 例患者，其中 13 例在阿法替尼进展后接受吡咯替尼治疗。阿法替尼进展后是否接受吡咯替尼治疗的患者，其吡咯替尼的无进展生存期（PFS）无统计学差异（6.7 个月比 4.4 个月，P=0.817），表明阿法替尼进展并不影响吡咯替尼的疗效。对前者进行进一步分析，其中 8 例患者在阿法替尼进展后接受间隔化疗。2 例患者在接受吡咯替尼治疗后获得 PR。未发现影响吡咯替尼 PFS 的独立因素。PDTO 证实了吡咯替尼在 HER2 扩增 NSCLC 肿瘤细胞中的抗肿瘤活性。
先前接受阿法替尼治疗后进展并不影响吡咯替尼治疗的疗效。吡咯替尼可能是阿法替尼进展后 HER2 突变患者的一种挽救治疗选择。
