Gautam Roy Prabhat, Reingold Davida, Pathak Neha, Verma Saurav, Gupta Aarushi, Meti Nicholas, Molto Consolacion, Malik Prabhat Singh, Linford Geordie, Mittal Abhenil
All India Institute of Medical Sciences, New Delhi 110029, India.
Department of Radiology, Health Sciences North, Northern Ontario School of Medicine, 41 Ramsey Lake Road, Sudbury, ON P3E 5J1, Canada.
Curr Oncol. 2025 Aug 9;32(8):448. doi: 10.3390/curroncol32080448.
The treatment landscape for EGFR-mutated metastatic non-small cell lung cancer (mNSCLC) has evolved significantly with multiple combination regimens demonstrating superiority over single agent Osimertinib over the past two years. Recent trials such as FLAURA2 and MARIPOSA have explored intensified front-line regimens, with FLAURA2 demonstrating improvement in PFS with the addition of chemotherapy to Osimertinib and MARIPOSA, showing both a PFS and OS benefit with a novel combination regimen of Amivantamab and Lazertinib. However, these regimens are associated with significantly higher toxicity to patients and pose a huge financial and logistical burden to the health care system; therefore, treatment selection must therefore be individualized, considering disease biology, patient fitness, and toxicity burden. Post-progression strategies remain challenging due to resistance mechanisms like EGFR C797S mutations and MET amplification and the lack of data post-progression on novel first-line combinations. Ongoing trials are investigating fourth-generation EGFR TKIs, MET inhibitors, antibody-drug conjugates, and bispecific antibodies in subsequent lines. While regimens like Amivantamab-Lazertinib show promise even in second-line settings, toxicity, cost, and access remain barriers. As therapeutic options expand, biomarker-driven sequencing and personalized care will be critical to optimizing long-term outcomes in EGFR-mutated mNSCLC.
在过去两年中，表皮生长因子受体（EGFR）突变的转移性非小细胞肺癌（mNSCLC）的治疗格局发生了显著变化，多种联合治疗方案已显示出优于单一药物奥希替尼的效果。近期的试验，如FLAURA2和MARIPOSA，探索了强化一线治疗方案，其中FLAURA2试验表明，在奥希替尼基础上加用化疗可改善无进展生存期（PFS），而MARIPOSA试验显示，新型联合治疗方案阿米万他单抗和拉泽替尼可同时带来PFS和总生存期（OS）获益。然而，这些治疗方案对患者的毒性显著更高，给医疗保健系统带来了巨大的经济和后勤负担；因此，治疗选择必须个体化，要考虑疾病生物学特性、患者健康状况和毒性负担。由于存在EGFR C797S突变和MET扩增等耐药机制，以及缺乏关于新型一线联合治疗方案进展后的相关数据，进展后治疗策略仍然具有挑战性。正在进行的试验正在研究后续治疗线中的第四代EGFR酪氨酸激酶抑制剂（TKIs）、MET抑制剂、抗体药物偶联物和双特异性抗体。虽然像阿米万他单抗-拉泽替尼这样的治疗方案即使在二线治疗中也显示出前景，但毒性、成本和可及性仍然是障碍。随着治疗选择的不断扩展，生物标志物驱动的测序和个性化治疗对于优化EGFR突变的mNSCLC的长期治疗效果至关重要。
