For critically ill patients with non-small cell lung cancer (NSCLC) in need of life-saving treatment, there is currently no reported evidence regarding the use of medication specifically targeting epidermal growth factor receptor (EGFR) p.C797S mutation, which is known to cause resistance to third-generation tyrosine kinase inhibitors (TKIs). Our report aims to investigate and explore treatment strategies to overcome resistance associated with EGFR p.C797S mutation in order to provide potential therapeutic options for these patients. Here, we reported two cases with NSCLC who initially harbored an EGFR-sensitive mutation and were both treated with osimertinib, a third-generation TKI. Next-generation sequencing tests conducted prior to the initiation of fifth-line therapy in critically ill patients revealed the presence of EGFR p.C797S mutations in both patients, suggesting acquired resistance. In the course of fifth-line therapy, the administration of a combination of brigatinib and cetuximab proved vital in saving critically ill patients, moderately extending their overall survival period. Our findings suggested that a combined regimen of brigatinib and cetuximab could serve as a potentially life-saving therapeutic strategy for critically ill patients with NSCLC, particularly those demonstrating EGFR p.C797S-mediated resistance. Further studies, however, are required to validate and expand upon these promising findings.

中文翻译：

---

布加替尼联合西妥昔单抗五线治疗EGFR p.C797S突变非小细胞肺癌危重患者2例报告及文献复习

对于需要挽救生命的治疗的危重非小细胞肺癌（NSCLC）患者，目前尚无关于使用专门针对已知表皮生长因子受体（EGFR）p.C797S突变的药物的报道证据引起对第三代酪氨酸激酶抑制剂（TKI）的耐药性。我们的报告旨在调查和探索克服 EGFR p.C797S 突变相关耐药性的治疗策略，以便为这些患者提供潜在的治疗选择。在此，我们报告了两例最初携带 EGFR 敏感突变的 NSCLC 病例，均接受了第三代 TKI 奥希替尼治疗。在危重患者开始五线治疗之前进行的下一代测序测试显示，两名患者均存在 EGFR p.C797S 突变，表明获得性耐药。在五线治疗过程中，布加替尼和西妥昔单抗联合用药对挽救危重患者至关重要，适度延长了他们的总生存期。我们的研究结果表明，布加替尼和西妥昔单抗的联合治疗方案可以作为 NSCLC 危重患者的潜在挽救生命的治疗策略，特别是那些表现出 EGFR p.C797S 介导的耐药性的患者。然而，需要进一步的研究来验证和扩展这些有希望的发现。