Two non-small cell lung cancer (NSCLC) patients with brain metastasis harboring epidermal growth factor receptor (EGFR) G719X and L861Q mutations benefited from aumolertinib: two cases report and review of the literature

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.