精准癌症医学改变了具有特定分子畸变的非小细胞肺癌（NSCLC）患者的治疗模式。一个主要挑战是通过原发性或获得性耐药机制来管理肿瘤细胞最终对靶向治疗产生的耐药性。我们报告了一名患有转移性 NSCLC 的 61 岁男性患者，其携带 EGFR 外显子 19 缺失、PIK3CA 突变和 CDK4 扩增。在对奥希替尼单一疗法（第三代 EGFR 酪氨酸激酶抑制剂）初步部分缓解后，患者在治疗 4 个月后疾病进展，并被转诊接受奥希替尼和帕博西尼（CDK4/6 抑制剂）联合治疗。虽然并发短暂性肺炎，但患者在 10 个月以上的时间内持续出现部分缓解，并且在该治疗方案中经历了临床改善。由于 CDK4 扩增发生在 EGFR 突变 NSCLC 初治患者中的 10% 左右，因此奥希替尼和帕博西尼对我们患者的成功治疗可能与未来的 NSCLC 患者高度相关。© 2024。作者。

Precision cancer medicine has changed the treatment paradigm of patients with non-small cell lung cancer (NSCLC) with specific molecular aberrations. A major challenge is management of the resistance that tumor cells eventually develop against targeted therapies, either through primary or acquired resistance mechanisms. We report a 61 year-old male patient with metastatic NSCLC harboring an EGFR exon 19 deletion, a PIK3CA mutation, and CDK4 amplification. After an initial partial response to osimertinib as mono-therapy (third-generation EGFR tyrosine kinase inhibitor), the patient had progression of disease after 4 months of treatment and was referred for combined osimertinib and palbociclib (CDK4/6 inhibitor) treatment. Though complicated by transient pneumonitis, the patient has an ongoing partial response for > 10 months and has experienced clinical improvement on this treatment regimen. As amplification of CDK4 occurs in ~ 10% of treatment-naïve patients with EGFR-mutated NSCLC, the successful treatment of our patient with osimertinib and palbociclib may be highly relevant for future patients with NSCLC.© 2024. The Author(s).