■尽管有驱动突变的患者从靶向治疗中获益显著,不可避免的耐药性通常发生在非小细胞肺癌中,强调序贯治疗延长总生存期的必要性。不幸的是,在对奥希替尼耐药后获得EML4-ALK融合的病例的后线治疗中,尚无持久药物反应的报道,敦促临床管理中需要有针对性的决策。
■我们介绍一例71岁的中国女性,从不吸烟,诊断为左肺下叶浸润性腺癌,区域淋巴结转移。通过对切除的肿瘤组织进行下一代测序,检测到共存的EGFRL858R/G719S和BRAFV600E后,患者接受了厄洛替尼治疗。常规成像显示疾病进展在开始厄洛替尼治疗后约14个月,然后通过非侵入性液体活检检测EGFRL858R。随后,奥希替尼给药,显示近19个月的临床活动,直到出现EML4-ALK融合。考虑到EML4-ALK融合,奥希替尼相对罕见的耐药机制,她接受了三线依萨替尼治疗.一个月后,减轻的肿瘤病变加上正常的血清标志物水平证明了ensartinib在克服对奥希替尼的耐药性方面的有效性.值得注意的是,对ensartinib的临床反应持续超过14个月,在奥希替尼失败病例中,优于先前报道的阿莱替尼和克唑替尼的疗效.截至2022年7月的最后一次随访,患者无复发迹象,生活质量良好。
■我们报道了一名在接受埃罗替尼和奥希替尼序贯治疗后出现获得性EML4-ALK融合的肺腺癌患者的三线恩萨替尼治疗。鉴于EML4-ALK融合蛋白作为奥希替尼的耐药机制非常罕见,ensartinib成为这一特定临床挑战的有希望的治疗选择,提供优越的疗效和良好的安全性。
UNASSIGNED: Despite significant benefits from targeted therapy in patients with driver mutations, inevitable drug resistance usually occurred in non-small cell lung cancer, highlighting the necessity for sequential treatments to prolong overall survival. Unfortunately, durable drug response has not been reported in posterior-line therapy of cases with acquired EML4-ALK fusion after resistance to
osimertinib, urging the need of referable decision-making in clinical management.
UNASSIGNED: We present a case of a 71-year-old Chinese female, never smoker, diagnosed with invasive adenocarcinoma in the left inferior lobe of her lung, with metastases in regional lymph nodes. She received erlotinib treatment after the detection of coexistent EGFR L858R/G719S and BRAF V600E via next-generation sequencing of resected tumor tissue. Routine imaging revealed disease progression approximately 14 months after starting erlotinib treatment, followed by the detection of EGFR L858R through non-invasive liquid biopsy. Subsequently,
osimertinib was administered, showing clinical activities for nearly 19 months until the emergence of an EML4-ALK fusion. Given the EML4-ALK fusion, a relatively rare resistance mechanism to
osimertinib, she received third-line ensartinib treatment. One month later, alleviated tumor lesions plus normal serum marker levels demonstrated the effectiveness of ensartinib in overcoming resistance to
osimertinib. Of note, the clinical response to ensartinib persisted for more than 14 months, superior to the previously reported efficacy of aletinib and crizotinib in osimertinib-failure cases. As of the last follow-up in July 2022, the patient showed no signs of recurrence and maintained a good life quality.
UNASSIGNED: We reported a third-line ensartinib therapy in a patient with lung adenocarcinoma who developed an acquired EML4-ALK fusion after sequential treatment with erlotinib and osimertinib. Given the rarity of the EML4-ALK fusion as a resistance mechanism to
osimertinib, ensartinib emerges as a promising treatment option for this specific clinical challenge, offering superior efficacy and good safety.