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Survival benefit with checkpoint inhibitors versus chemotherapy is modified by brain metastases in patients with recurrent small cell lung cancer

INTRODUCTION: Small cell lung cancer (SCLC) is a rapidly growing malignancy with early distant metastases. Up to 70% will develop brain metastases, and the poor prognosis of these patients has not changed considerably. The potential of checkpoint inhibitors (CPI) in treating recurrent (r/r) SCLC and...

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Detalles Bibliográficos
Autores principales: Althoff, Friederike C., Schäfer, Lisa V., Acker, Fabian, Aguinarte, Lukas, Heinzen, Sophie, Rost, Maximilian, Atmaca, Akin, Rosery, Vivian, Alt, Jürgen, Waller, Cornelius F., Reinmuth, Niels, Rohde, Gernot, Saalfeld, Felix C., Becker von Rose, Aaron, Möller, Miriam, Frost, Nikolaj, Sebastian, Martin, Stratmann, Jan A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10556470/
https://www.ncbi.nlm.nih.gov/pubmed/37810988
http://dx.doi.org/10.3389/fonc.2023.1273478
Descripción
Sumario:INTRODUCTION: Small cell lung cancer (SCLC) is a rapidly growing malignancy with early distant metastases. Up to 70% will develop brain metastases, and the poor prognosis of these patients has not changed considerably. The potential of checkpoint inhibitors (CPI) in treating recurrent (r/r) SCLC and their effect on brain metastases remain unclear. METHODS: In this retrospective multicenter study, we analyzed r/r SCLC patients receiving second or further-line CPI versus chemotherapy between 2010 and 2020. We applied multivariable-adjusted Cox regression analysis to test for differences in 1-year mortality and real-world progression. We then used interaction analysis to evaluate whether brain metastases (BM) and/or cranial radiotherapy (CRT) modified the effect of CPI versus chemotherapy on overall survival. RESULTS: Among 285 patients, 99 (35%) received CPI and 186 (65%) patients received chemotherapy. Most patients (93%) in the CPI group received nivolumab/ipilimumab. Chemotherapy patients were entirely CPI-naïve and only one CPI patient had received atezolizumab for first-line treatment. CPI was associated with a lower risk of 1-year mortality (adjusted Hazard Ratio [HR(adj)] 0.59, 95% CI 0.42 to 0.82, p=0.002). This benefit was modified by BM and CRT, indicating a pronounced effect in patients without BM (with CRT: HR(adj) 0.34, p=0.003; no CRT: HR(adj) 0.50, p=0.05), while there was no effect in patients with BM who received CRT (HR(adj) 0.85, p=0.59). CONCLUSION: CPI was associated with a lower risk of 1-year mortality compared to chemotherapy. However, the effect on OS was significantly modified by intracranial disease and radiotherapy, suggesting the benefit was driven by patients without BM.