Osimertinib for the treatment of epidermal growth factor receptor-mutated non-small cell lung cancer patients with leptomeningeal metastases and different T790M status

Haiyan Xu; Hengqi Chen; Jianxin Kong; Ye Zhang; Shan Liu; Guangjian Yang; Lu Yang; Yan Wang

doi:10.21037/atm-21-1249

Osimertinib for the treatment of epidermal growth factor receptor-mutated non-small cell lung cancer patients with leptomeningeal metastases and different T790M status

Ann Transl Med. 2021 Jun;9(11):937. doi: 10.21037/atm-21-1249.

Authors

Haiyan Xu¹, Hengqi Chen², Jianxin Kong³, Ye Zhang⁴, Shan Liu¹, Guangjian Yang⁵, Lu Yang⁵, Yan Wang⁵

Affiliations

¹ Department of Comprehensive Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² Thoracic Surgery Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
³ Department of Neurosurgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁴ Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁵ Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Abstract

Background: Leptomeningeal metastasis (LM) is a catastrophic complication for patients with non-small cell lung cancer (NSCLC) and carries an extremely poor prognosis. The efficacy of osimertinib 80 mg once daily for epidermal growth factor receptor-mutated (EGFRm) NSCLC with LM has yet to be fully assessed. This study aimed to investigate the efficacy of osimertinib in such patients and their genetic profiles at the time of LM diagnosis.

Methods: From January 2016 to April 2020, pretreated EGFRm NSCLC patients who had progressed with cytologically confirmed symptomatic LM and received osimertinib 80 mg once daily were enrolled retrospectively. The objective response rate (ORR) and disease control rate (DCR) were evaluated, along with progression-free survival (PFS) and overall survival (OS). Next-generation sequencing of paired samples of cerebrospinal fluid and plasma collected at LM diagnosis was performed simultaneously.

Results: Forty cases of EGFRm lung adenocarcinoma with LM were analyzed. Females accounted for 75.0% of enrollees. Of the patients, 37.5% had a poor Eastern Cooperative Oncology Group score (≥2). Twelve patients had received at least 2 prior lines of treatment. All patients received osimertinib treatment regardless of their T790M status. According to the Response Assessment in Neuro-Oncology (RANO)-LM criteria, the ORR and DCR were 20.0% and 95.0%, respectively. The median PFS and OS were 10.0 (95% CI: 7.7-12.3) and 15.1 months (95% CI: 11.0-19.4), respectively. No significant difference was observed between T790M-negative patients (n=24) and T790M-positive patients (n=16) with respect to PFS [median, 10.8 (95% CI: 7.7-13.8) vs. 8.8 months (95% CI: 7.3-10.3), HR=0.595, P=0.158] or OS [median, 17.2 (95% CI: 8.7-25.7) vs. 11.4 months (95% CI: 3.9-19.0), HR=0.913, P=0.822]. The detection rate of EGFR sensitizing mutations in cerebrospinal fluid was higher than that in plasma (97.5% vs. 50%, P=0.311), whereas the incidence of T790M detection in cerebrospinal fluid was significantly lower than that in plasma (20.0% vs. 32.5%, P=0.043).

Conclusions: Osimertinib 80 mg once daily shows good efficacy in pretreated EGFRm NSCLC patients with LM regardless of their T790M status. Combining cerebrospinal fluid and plasma testing can aid in revealing more genetic information.

Keywords: EGFR; Non-small cell lung cancer (NSCLC); cerebrospinal fluid; leptomeningeal metastasis (LM); osimertinib.