SCI

19 June 2024

Phase II Efficacy and Safety of 80 mg Osimertinib in Patients With Leptomeningeal Metastases Associated With Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer (BLOSSOM)

（Journal of clinical oncology；IF：45.3）

  • Park S, Baldry R, Jung HA, Sun JM, Lee SH, Ahn JS, Kim YJ, Lee Y, Kim DW, Kim SW, Lee KH, Lee WJ, Choi JW, Chong K, Lee JI, Gwon SH, Son NH, Ahn MJ. Phase II Efficacy and Safety of 80 mg Osimertinib in Patients With Leptomeningeal Metastases Associated With Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer (BLOSSOM). J Clin Oncol. 2024 Jun 3:JCO2400708. doi: 10.1200/JCO.24.00708. Epub ahead of print. PMID: 38828959.

  • CORRESPONDING AUTHOR ：Myung-Ju Ahn, MD, PhD; e-mail: silkahn@skku.edu.Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

Purpose 目的

Leptomeningeal metastases (LMs) exhibit a high incidence in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) post-treatment with first- or second-generation EGFR tyrosine kinase inhibitors (TKIs). This investigation evaluates the efficacy, safety, and pharmacokinetics of 80 mg once daily osimertinib in patients with LMs resistant to prior first- or second-generation EGFR TKIs.

在表皮生长因子受体(EGFR)突变的非小细胞肺癌(NSCLC)患者接受第一代或第二代EGFR酪氨酸激酶抑制剂(TKIs)治疗后，脑膜转移(LMs)的发生率很高。本研究评估了80mg每日的奥希替尼对既往第一代或第二代EGFR TKIs耐药的LMs患者的有效性、安全性和药代动力学。

 

Materials and methods 材料和方法

In this phase II multicenter, open-label, single-arm study, 80 mg osimertinib was administered to patients with EGFR-mutated NSCLC who had developed LMs subsequent to treatment with prior EGFR TKIs. The primary end point was overall survival (OS), assessed alongside objective response rate by the blinded independent central review (BICR) and a pharmacokinetic analysis of plasma and cerebrospinal fluid (CSF) on the first day of cycles 3 and 6.

在这项II期多中心、开放标签、单臂临床研究中，给予先前使用EGFR TKIs治疗后发生LMs的EGFR突变的NSCLC患者80mg奥希替尼。主要终点是总生存期(OS)，通过盲态独立中心评估(BICR)和第3和第6周期首日血浆和脑脊液(CSF)的药代动力学分析评估客观缓解率。

 

Results 结果

A total of 73 patients diagnosed with LM were treated with osimertinib, including 64 patients evaluable for the LM efficacy set-T790M negative (n = 62) and T790M positive (n = 2). The median OS in the full-analysis set was 15.6 months (95% CI, 11.5 to 20.2). The objective response rate for LM was 51.6%, including a 15.6% complete response, and the disease control rate was 81.3% by BICR in the LM efficacy evaluable set. The median LM progression-free survival by BICR was 11.2 months (95% CI, 7.7 to 15.3), the duration of response was 12.6 months (95% CI, 7.6 to 17.7), and OS was 15.0 months (95% CI, 11.3 to 18.7). Pharmacokinetic analysis showed that the CSF to free plasma osimertinib ratio was 22%. Most safety profiles were grade 1 and 2.

共有73例诊断为LM的患者接受了奥希替尼治疗，其中64例患者可评估LM疗效，T790M阴性(n = 62)和T790M阳性(n = 2)。全分析集的中位生存期为15.6个月(95% CI, 11.5至20.2)。LM的客观缓解率为51.6%，其中完全缓解率为15.6%，BICR在LM疗效可评估集中的疾病控制率为81.3%。BICR的中位无进展生存期为11.2个月(95% CI, 7.7至15.3)，缓解持续时间为12.6个月(95% CI, 7.6至17.7)，OS为15.0个月(95% CI, 11.3至18.7)。药代动力学分析显示脑脊液与游离血浆奥希替尼的比值为22%。大多数安全概况为1级和2级。

 

Conclusion 结论

The study demonstrates significant intracranial efficacy and survival benefits of 80 mg once daily osimertinib in NSCLC patients with LMs. The data support considering daily 80 mg of osimertinib as a treatment option for EGFR-mutated NSCLC patients with LMs, irrespective of T790M mutation status.

本研究显示，80mg每日一次的奥希替尼对伴有LMs的NSCLC患者有显著的颅内疗效和生存获益。数据支持认为每日80mg奥希替尼作为EGFR突变的LMs NSCLC患者的治疗选择，无论T790M是否存在突变。

 

Trial registration 试验注册

ClinicalTrials.gov NCT04563871.

ClinicalTrials.gov NCT04563871。