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

Background: 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-naive 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.