Li Lin
Jiangxi Cancer Hospital, China.
Heliyon. 2022 Aug 28;8(9):e10407. doi: 10.1016/j.heliyon.2022.e10407. eCollection 2022 Sep.
The third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) established a new standard for EGFR mutation positive non-small cell lung cancer (NSCLC) treatment. Brain metastases (BMS) are common in NSCLCs with poor prognosis, and patients with BMS who carry uncommon mutations is lack of treatment options. Aumolertinib is the first third-generation EGFR TKI in China and the second in the global context. There are few reports of the efficacy of aumolertinib in treating NSCLC patients with BMS who harboring uncommon EGFR mutations, which is needs to be investigated. Here we reported two cases of aumolertinib in treating NSCLC patients with BMS harboring EGFR G719X/L861Q mutations. The first one was diagnosed with poorly differentiated stage IVB adenocarcinoma with brain metastases. Genetic tests showed mutations in exons of EGFR 18 (G719D) and 21 (L861Q) initially. The patient was administered with pemetrexed 0.8 g and lobaplatin 30 mg, and aumolertinib (110 mg QD) combined with one-month of WBRT(Whole Brain Radiation Therapy) (42 Gy in 7 fractions). In order to avoid the side effects of radiotherapy on brain, radiotherapy was discontinued on February 5, 2020. The regime was continued with pemetrexed 0.75 g, lobaplatin 30 mg, bevacizumab 400 mg, and aumolertinib 110 mg QD. The four-drug combination regimen lasted for 6 months until serum tumor markers were elevated slightly. Then lobaplatin was replaced with nedaplatin, and the new four-drug combination regimen (pemetrexed 0.75 g, nedaplatin 90mg, bevacizumab 400 mg, and aumolertinib 110mg QD) was used with a one-month cycle for 3 cycles. Aumolertinib was administered daily throughout the four-drug combination, with the rest administered on day 1 of this treatment cycle. Chest CT scan were performed each month, which showed no progressed of lung disease. The patient had a progression-free survival of 13 months and is still being treated with aumolertinib. The second patient was diagnosed as right lung adenocarcinoma (T3N2M1) IVB secondary bone and brain malignancy carrying EGFR 18 (G719A) and 21 (L861Q) exon mutation. Aumolertinib combined with local radiotherapy was used after failure of afatinib combined with radiotherapy. Follow-up chest CT and brain MRI revealed that the lung lesions were partially relieved. Furthermore, the multiple nodules in the brain were relieved and cerebral edema was reduced. The aumolertinib monotherapy was continued, and follow-up imaging showed no disease progression. PFS was 13 months during the treatment with aumolertinib. The two cases showed good efficacy of aumolertinib in treating patients with brain metastases (BMS) that harbored EGFR 18 (G719X) and 21 (L861Q) mutations.
第三代表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂（TKIs）为EGFR突变阳性非小细胞肺癌（NSCLC）的治疗树立了新标准。脑转移（BMS）在NSCLC中很常见，预后较差，而携带罕见突变的BMS患者缺乏治疗选择。奥莫替尼是中国首个第三代EGFR TKI，在全球范围内是第二个。关于奥莫替尼治疗携带罕见EGFR突变的NSCLC合并BMS患者疗效的报道很少，这需要进行研究。在此，我们报告了两例奥莫替尼治疗携带EGFR G719X/L861Q突变的NSCLC合并BMS患者的病例。第一例被诊断为低分化IVB期腺癌伴脑转移。基因检测最初显示EGFR 18外显子（G719D）和21外显子（L861Q）突变。患者接受培美曲塞0.8 g和洛铂30 mg，并给予奥莫替尼（110 mg每日一次）联合为期一个月的全脑放射治疗（WBRT）（42 Gy分7次）。为避免放疗对脑部的副作用，于2020年2月5日停止放疗。继续使用培美曲塞0.75 g、洛铂30 mg、贝伐单抗400 mg和奥莫替尼110 mg每日一次的方案。四联方案持续6个月，直到血清肿瘤标志物略有升高。然后将洛铂换为奈达铂，新的四联方案（培美曲塞0.75 g、奈达铂90mg、贝伐单抗400 mg和奥莫替尼110mg每日一次）以一个月为周期使用3个周期。在四联治疗期间奥莫替尼每日给药，其余药物在该治疗周期的第1天给药。每月进行胸部CT扫描，显示肺部疾病无进展。该患者无进展生存期为13个月，目前仍在接受奥莫替尼治疗。第二例患者被诊断为右肺腺癌（T3N2M1）IVB期，继发骨和脑恶性肿瘤，携带EGFR 18外显子（G719A）和21外显子（L861Q）突变。在阿法替尼联合放疗失败后，使用奥莫替尼联合局部放疗。随访胸部CT和脑部MRI显示肺部病变部分缓解。此外，脑部多个结节缓解，脑水肿减轻。继续奥莫替尼单药治疗，随访影像学显示无疾病进展。奥莫替尼治疗期间无进展生存期为13个月。这两例病例显示奥莫替尼治疗携带EGFR 18（G719X）和21（L861Q）突变的脑转移（BMS）患者疗效良好。
