Forthcoming Phase II Study of Durvalumab (MEDI4736) Plus Chemotherapy for Small Cell Lung Cancer with Brain Metastases

Yoshimasa Shiraishi,1 Takayuki Shimose,2 Yuko Tsuchiya-Kawano,3 Hidenobu Ishii,4 Haruko Daga,5 Kentaro Ito,6 Koichi Saruwatari,7 Isamu Okamoto1 1Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; 2Department of Statistics and Data Center, Clinical Research Support Center Kyushu, Fukuoka, Japan; 3Department of Respiratory Medicine, Kitakyushu Municipal Medical Center, Kitakyushu, Japan; 4Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan; 5Department of Medical Oncology, Osaka City General Hospital, Osaka, Japan; 6Respiratory Center, Matsusaka Municipal Hospital, Mie, Japan; 7Department of Respiratory Medicine, Kumamoto University Hospital, Faculty of Life Sciences, Kumamoto University, Kumamoto, JapanCorrespondence: Isamu Okamoto, Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan, Tel +81-92-642-5378, Fax +81-92-642-5390, Email okamoto.isamu.290@m.kyushu-u.ac.jpBackground: 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.Patients and Methods: 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.Conclusion: 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.Keywords: immune checkpoint inhibitor, PD-L1, intracranial metastasis, intracranial response rate, platinum-etoposide