Delayed central nervous system progression with atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer (LU23-15)

Abstract

BACKGROUND: The combination of atezolizumab with etoposide and carboplatin (AECb) has become a new standard of care for extensive-stage small-cell lung cancer (ES-SCLC). This study evaluates its impact on central nervous system (CNS) progression, specifically brain metastases. METHOD: We analyzed the outcomes of 550 ES-SCLC patients who received first-line therapy between 2016 and 2022, focusing on time to intracranial progression (TTicP), progression-free survival (PFS), and overall survival (OS). RESULTS: Of the 550 patients, 247 (44.9 %) received AECb, while 303 (55.1 %) received conventional chemotherapy (CTx). Intracranial progression occurred in 179 patients (32.5 %), with the AECb group showing a significantly prolonged TTicP compared to the CTx group (median 24.4 vs. 14.3 months; p = 0.038). In patients without brain metastasis at diagnosis (n = 408), TTicP was also longer in the AECb group (27.2 vs. 15.3 months; p = 0.016). This benefit persisted even after excluding patients who underwent prophylactic cranial irradiation (PCI) (27.2 vs. 15.2 months; p = 0.02) (n = 394). These findings remained consistent after adjusting for age, initial metastatic site, and PCI. Additionally, the AECb group showed improved PFS (5.0 vs. 4.7 months; p = 0.004) and OS (11.1 vs. 9.8 months; p = 0.003). CONCLUSION: Our findings suggest that the AECb regimen is superior to conventional chemotherapy in delaying CNS progression and controlling systemic disease in ES-SCLC. These results support the AECb regimen as the new standard of care. Further research is needed to explore the mechanisms behind these improved CNS outcomes and to reassess the necessity of PCI in this treatment era.