A 38-year-old, never-smoker female had been treated for pulmonary tuberculosis for 3 months but had not improved. By bronchoscopic biopsy, NSCLC was diagnosed, and multiple bone metastases were detected in the imaging workup. As an EGFR L868R mutation was confirmed by biopsy specimen, gefitinib was started in November 2018. Six months later, the disease had progressed, and the repeat biopsy was performed by endobronchial ultrasound-guided transbronchial needle aspiration, and an EGFR T790M mutation was not detected. The metastatic brain lesion was also identified in brain MRI and treated with GKS. Next, the patient was treated with a combination of atezolizumab, bevacizumab, paclitaxel, and carboplatin followed by atezolizumab and bevacizumab maintenance. However, in December 2019, the patient complained of nausea, vomiting, and headache, and LM was diagnosed with brain MRI and CSF cytology. Thus, osimertinib 80 mg once daily combined with pemetrexed were started. With osimertinib and systemic chemotherapy, the patient complained of myalgia and abdominal pain. However, the adverse events were well controlled with supportive care. Unfortunately, the extracranial disease was refractory, leading to additional regimen changes (docetaxel followed by gemcitabine and carboplatin). LM was uncontrolled, so additional WBRT and VP shunt insertion were necessary. Nevertheless, she died of extracranial disease progression in May 2021. Images of the chest CT and brain MRI before and after osimertinib administration are presented in Fig. 1D.
Patient characteristics and prior treatments are described in Table 1. In four reviewed cases, median follow-up duration was 37.7 months (range, 18.1 to 54.6 months) from the date of initial diagnosis of NSCLC and 12.0 months (range, 7.1 to 17.3 months) from the date of LM progression. The median time from initial diagnosis of NSCLC to LM progression was 25.5 months (range, 5.1 to 43.6 months), and the median treatment duration of osimertinib was 9.7 months (range, 6.0 to 16.8 months). On 30 August 2021, only one patient (case 2) was alive and had been ongoing treatment with osimertinib for more than 6 months combined with systemic chemotherapy. The other three patients died of LM progression. Mean OS was 49.2 (95% CI, 41.8 to 56.7) from initial NSCLC diagnosis and 14.7 months (95% CI, 10.4 to 19.0) from LM progression. Median OS from initial NSCLC diagnosis was 43.8 months (95% CI, not reached), and median OS from LM progression was not reached.
There was no >= 3 grade adverse event noted in the four cases, and there was one case of dose reduction due to grade 2 diarrhea (case 2). The most common adverse event was abdominal pain, which was noted in two patients (cases 3 and 4) but was well controlled with conservative care.