Osimertinib in combination with bevacizumab in EGFR-Mutated NSCLC with leptomeningeal metastases

Transl Lung Cancer Res 2020;9(6):2514-2517 | http://dx.doi.org/10.21037/tlcr-20-984 Leptomeningeal metastases (LM) occur in approximately 5–15% of non-small-cell lung cancer (NSCLC) patients with EGFR mutations together with very poor prognosis, and there is no broadly accepted standard treatment (1). Although new-generation EGFR-TKIs have significantly prolonged both progression-free survival (PFS) and overall survival (OS) in patients with EGFR-mutated NSCLC (2,3), little is known about the efficacy of novel EGFRTKIs (e.g., osimertinib) for patients with LM. Recently, Lee et al. compared the clinical outcomes of patients with EGFR-mutated NSCLC and LM received osimertinib with those not receive osimertinib in the Journal of Thoracic Oncology (4). Their data showed that patients with LM received osimertinib had significantly longer OS than those not treated with osimertinib (17.0 vs. 5.5 months, P<0.001), which suggested that osimertinib would be a good therapeutic option for patients with EGFR-mutated NSCLC and LM. Moreover, two recent publications suggested that combining EGFR-TKIs and bevacizumab may be efficacious for brain metastases (BMs) and protective against central nervous system (CNS) progression (5,6). Herein, we presented one case to further investigate the efficacy and tolerability of osimertinib plus bevacizumab for patient with EGFR-mutated NSCLC and cytologically proven LM. This patient was a 47-year-old male smoker consulted our hospital with 3-week history of cough and chest distress in September 2019. The thoracic computed tomography (CT) scan found a mass in the lower lobe of the right lung (Figure 1A). Multiple BMs and abnormal signal on meninges of cerebellum were seen in magnetic resonance imaging (MRI) scan, but F-deoxyglucose on positron emission tomography (PET) scan did not find other distant metastases. Bronchoscopy biopsy and cytology of cerebrospinal fluid (CSF) revealed lung adenocarcinoma (Figure 1B). Subsequent genotype of primary lesion revealed EGFR exon 19 deletion, which was confirmed by targeted next-generation sequencing (NGS) panel of 139 genes (PULMOCAN, GENESEEQ Technology Inc., Nanjing, China) of CSF cytologic specimen (Figure 1B). The patients suffered headache and violent vomiting during hospitalization. Then he received osimertinib (80 mg, once daily) plus bevacizumab (7.5 mg/kg, 21-day cycle) as the first-line treatment from October 2, 2019. Strikingly, the abnormal signal on LM disappeared (Figure 1A) and his LM-related symptoms significantly improved. A marked shrinkage of both primary lesion and BMs was also observed after 6 weeks of osimertinib plus bevacizumab treatment (Figure 1A). Moreover, the efficacy has been maintained more than 10 months (last follow-up: August 8, 2020). This regimen was well tolerated, with only grade 2 skin rash and grade 1 hypertension during regular follow-up. In previous study, 22 NSCLC patients (previously received EGFR-TKIs, from the AURA program) with EGFR T790M mutation and radiologically-detected LMs were treated with osimertinib (80 mg once daily). LM ORR Letter to the Editor