Shiraishi Yoshimasa, Shimose Takayuki, Tsuchiya-Kawano Yuko, Ishii Hidenobu, Daga Haruko, Ito Kentaro, Saruwatari Koichi, Okamoto Isamu
Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Statistics and Data Center, Clinical Research Support Center Kyushu, Fukuoka, Japan.
Cancer Manag Res. 2022 Dec 14;14:3449-3453. doi: 10.2147/CMAR.S391220. eCollection 2022.
The standard of care for extensive-stage small cell lung cancer (ES-SCLC) is an immune checkpoint inhibitor (ICI) combined with platinum-etoposide (PE) chemotherapy. At initial diagnosis, about 25% of ES-SCLC patients have brain metastases, which are associated with a poor prognosis. The decision as to whether to treat brain metastases with local therapies such as surgery or radiotherapy before initiation of systemic chemoimmunotherapy is based on symptoms due to the brain lesions and the general condition of the patient. Subset analysis of the CASPIAN study showed that combination therapy with PE plus durvalumab (MEDI4736) is promising for ES-SCLC with brain metastases. However, data required in daily clinical practice, such as intracranial response rate and duration of intracranial response, are insufficient for such patients.
We have designed a single-arm phase II trial of durvalumab plus PE for patients aged ≥20 years with chemotherapy-naïve ES-SCLC and at least one brain metastasis ≥5 mm in size that has not been previously treated. Patients receive durvalumab intravenously combined with four cycles of PE. Enrollment of 50 patients over 2 years at 25 oncology facilities in Japan is planned. The primary endpoint is intracranial response rate.
This is the first prospective study to evaluate the effects of an ICI with PE specifically in ES-SCLC patients with brain metastases. If it demonstrates intracranial efficacy, this regimen will be a potential treatment option for such individuals, and radiation therapy or surgery for brain metastases can be avoided or postponed.
广泛期小细胞肺癌（ES-SCLC）的标准治疗方案是免疫检查点抑制剂（ICI）联合铂类-依托泊苷（PE）化疗。在初始诊断时，约25%的ES-SCLC患者有脑转移，这与预后不良相关。在开始全身化疗免疫治疗之前，决定是否采用手术或放疗等局部治疗来治疗脑转移，是基于脑病变引起的症状和患者的一般状况。CASPIAN研究的亚组分析表明，PE联合度伐利尤单抗（MEDI4736）的联合治疗方案对有脑转移的ES-SCLC有前景。然而，日常临床实践中所需的数据，如颅内缓解率和颅内缓解持续时间，对于这类患者来说并不充分。
我们设计了一项单臂II期试验，用于治疗年龄≥20岁、未经化疗的ES-SCLC且至少有一处≥5mm大小且此前未接受过治疗的脑转移的患者，给予度伐利尤单抗加PE治疗。患者接受静脉注射度伐利尤单抗并联合四个周期的PE治疗。计划在日本的25个肿瘤治疗机构在2年内招募50名患者。主要终点是颅内缓解率。
这是第一项专门评估ICI联合PE对有脑转移的ES-SCLC患者疗效的前瞻性研究。如果它显示出颅内疗效，该方案将成为这类患者的一种潜在治疗选择，并且可以避免或推迟对脑转移进行放射治疗或手术。
