A phase II study of Osimertinib for patients with radiotherapy-naïve CNS metastasis of non-small cell lung cancer: treatment rationale and protocol design of the OCEAN study (LOGIK 1603/WJOG 9116L)

BMC Cancer

Kenichi Yoshimura¹  Satoru Miura²  Kazuhiko Nakagawa³  Noriyuki Ebi⁴  Masafumi Takeshita⁵  Osamu Hataji⁶  Minoru Fukuda⁷  Hiroyuki Yamaguchi⁸  Kenji Chibana⁹  Takayuki Suetsugu^1,10  Keisuke Kirita^1,11  Kenji Sugio^1,12  Kazushige Wakuda^1,13  Hirotsugu Kenmotsu^1,13  Nobuyuki Yamamoto^1,14  Isamu Okamoto^1,15 

[1] Department of Biostatistics, Innovative Clinical Research Center, Kanazawa University Hospital;Department of Internal Medicine, Niigata Cancer Center Hospital;Department of Medical Oncology, Kindai University Faculty of Medicine;Department of Respiratory Medicine, Iizuka Hospital;Department of Respiratory Medicine, Kitakyushu Municipal Medical Center;Department of Respiratory Medicine, Matsusaka Municipal Hospital Respiratory Center;Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences and Clinical Oncology Center;Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences;Department of Respiratory Medicine, National Hospital Organization, Okinawa National Hospital;Department of Respiratory Medicine, Sendai Medical Association Hospital;Department of Thoracic Oncology, National Cancer Center Hospital East;Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine;Division of Thoracic Oncology, Shizuoka Cancer Center Hospital;Internal Medicine III, Wakayama Medical University;Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University;

关键词: Non-small cell lung cancer;    EGFR T790M;    CNS metastasis;    Brain metastasis;    Osimertinib;   

DOI  :  10.1186/s12885-020-06874-6

来源: DOAJ

【 摘 要 】

Abstract Background Patients with activating epidermal growth factor receptor (EGFR) mutations are highly responsive to EGFR-tyrosine kinase inhibitors (TKIs). However, it has been reported that approximately 15–30% of patients treated with EGFR-TKIs experience central nervous system (CNS) progression, and patients with EGFR mutations exhibit a higher incidence of brain metastasis than those without such mutations. The efficacy of osimertinib for treating CNS metastasis has been reported, but its efficacy for CNS metastasis in radiotherapy-naïve patients is unclear. Methods In the present prospective two-cohort phase II trial, 65 patients (T790M cohort, 40 patients; first-line cohort, 25 patients) with radiotherapy-naïve CNS metastasis of EGFR mutation-positive non-small cell lung cancer (NSCLC) will be included. Patients will be treated once-daily with osimertinib 80 mg. The primary endpoint is the response rate of brain metastasis as assessed using the PAREXEL criteria. Key secondary endpoints are progression-free survival and the response rate of brain metastasis as assessed using the RECIST criteria. We will exploratorily analyze the relationships of the blood concentration of osimertinib with its efficacy against brain metastasis of NSCLC and the accumulation of osimertinib in cerebrospinal fluid and evaluate tumor-derived DNA from plasma specimens for mutations in EGFR and other genes. Recruitment, which in October 2016, is ongoing. Discussion Although previous reports revealed the efficacy of osimertinib for CNS metastasis, these reports only involved subgroup analysis, and the efficacy of osimertinib for patients with previously untreated CNS metastasis remains unclear. The OCEAN study is the only trial of osimertinib for patients with untreated brain metastasis of NSCLC. This study should provide novel data about osimertinib. If the results of the OCEAN study are positive, then avoidance of radiotherapy will be recommended to patients harboring EGFR mutations and brain metastasis. Trial registration UMIN identifier: UMIN000024218 (date of initial registration: 29 September 2016). jRCT identifier: jRCTs071180017 (date of initial registration: 13 February 2019).

【 授权许可】

Unknown