Guo Yongkuan, Zhang Ran, Meng Yiran, Wang Li, Zheng Liuqing, You Jian
Department of Thoracic Oncology, Tianjin Cancer Hospital Airport Hospital, National Clinical Research Center for Cancer, Tianjin, China.
Hangzhou Repugene Technology Co., Ltd., Hangzhou, China.
Front Pharmacol. 2024 Jul 29;15:1359403. doi: 10.3389/fphar.2024.1359403. eCollection 2024.
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 fusion after resistance to osimertinib, urging the need of referable decision-making in clinical management.
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 L858R/G719S and 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 L858R through non-invasive liquid biopsy. Subsequently, osimertinib was administered, showing clinical activities for nearly 19 months until the emergence of an fusion. Given the 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.
We reported a third-line ensartinib therapy in a patient with lung adenocarcinoma who developed an acquired fusion after sequential treatment with erlotinib and osimertinib. Given the rarity of the 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.
尽管针对具有驱动基因突变的患者进行靶向治疗有显著益处，但非小细胞肺癌中不可避免地会出现耐药，这凸显了序贯治疗以延长总生存期的必要性。不幸的是，在对奥希替尼耐药后出现获得性融合的病例的后线治疗中，尚未有持久药物反应的报道，这促使在临床管理中需要可参考的决策。
我们报告一例71岁从未吸烟的中国女性，被诊断为左肺下叶浸润性腺癌伴区域淋巴结转移。通过对切除的肿瘤组织进行二代测序检测到共存的L858R/G719S和V600E后，她接受了厄洛替尼治疗。常规影像学检查显示在开始厄洛替尼治疗约14个月后疾病进展，随后通过非侵入性液体活检检测到L858R。随后给予奥希替尼治疗，显示出近19个月的临床活性，直至出现一种融合。鉴于这种融合是奥希替尼相对罕见的耐药机制，她接受了三线恩沙替尼治疗。1个月后，肿瘤病灶减轻且血清标志物水平正常，证明恩沙替尼在克服对奥希替尼的耐药方面有效。值得注意的是，对恩沙替尼的临床反应持续超过14个月，优于先前报道的阿来替尼和克唑替尼在奥希替尼治疗失败病例中的疗效。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。
我们报告了一例肺腺癌患者在接受厄洛替尼和奥希替尼序贯治疗后出现获得性融合，接受三线恩沙替尼治疗的病例。鉴于这种融合作为奥希替尼耐药机制的罕见性，恩沙替尼成为应对这一特定临床挑战的有前景的治疗选择，具有卓越的疗效和良好的安全性。
