Intracranial efficacy of combined immune checkpoint inhibitors and platinum plus etoposide therapy in patients with extensive-disease small-cell lung cancer and brain metastases

BACKGROUND: The management of brain metastases remains a major challenge in extensive-disease small-cell lung cancer (ED-SCLC). Although immune checkpoint inhibitor (ICI) therapy combined with etoposide and platinum (EP) is the standard treatment for ED-SCLC, its intracranial efficacy remains unclear. This study evaluated the efficacy of combined ICI and EP therapy, with a focus on intracranial response. METHODS: We retrospectively included 59 patients with ED-SCLC and brain metastases who received combined ICI and EP therapy. Efficacy endpoints included objective response rates (ORRs), progression-free survival (PFS), and overall survival (OS). The ORR and PFS were evaluated separately for intracranial (i) and extracranial (e) lesions. We also evaluated survival according to upfront brain radiotherapy (BRT) use prior to systemic chemotherapy. RESULTS: Patients with a performance status of 2 or 3 accounted for 27 % of the cohort. Nineteen patients (32 %) had symptomatic brain metastases. The iORR and eORR were 73 % and 78 %, respectively (p = 0.42). The median iPFS was 6.3 months (95 % confidence intervals [CI]: 4.5-8.0), comparable to the median ePFS of 5.2 months (95 % CI: 4.0-6.4). In survival analyses by upfront BRT, the median iPFS was numerically longer in the BRT group than in the non-BRT group (9.7 vs. 5.7 months, p = 0.09). The median OS did not differ significantly between the BRT and non-BRT groups (11.6 months vs. 10.9 months; p = 0.26). CONCLUSION: Combined ICI and EP therapy demonstrated favorable intracranial efficacy. OS was similar regardless of upfront BRT, supporting this regimen as a valuable treatment option for ED-SCLC with brain metastases.