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A Retrospective Study of Brain Metastases From Solid Malignancies: The Effect of Immune Checkpoint Inhibitors
Wei Du1, Cristian Sirbu1, B Daniel Lucas1
1Charleston Area Medical Center (CAMC) Health Education and Research Institute, Charleston, WV, United States.
Introduction:
Brain metastases (BM) are associated with dismal prognosis, and there is a dearth of effective systemic therapy. In this study, patients with BM from multiple solid tumors were identified from TriNetX databases, their clinicopathological features were evaluated, and the effects of immune checkpoint inhibitor (ICI) therapy were assessed.
Methods:
Variables, including median overall survival (OS), Eastern Cooperative Oncology Group (ECOG) performance status, primary diagnosis, and date of diagnosis, were retrieved from TriNetX, a real-world database. Kaplan-Meier plots and log-rank tests were applied to assess significance of differences in survival. Hazard ratio (HR) and 95% confidence interval (CI) values were calculated. All patient data were deidentified.
Results:
A total of 227,255 patients with BM were identified in the TriNetX database; median OS was 12.3 months from initial cancer diagnosis and 7.1 months from development of BM. OS of BM from nonsmall-cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), melanoma, and renal cell carcinoma (RCC) were 8.7, 14.7, 17.8, and 15.6 months, respectively. After matching patient baseline characteristics, OS of cohorts with or without exposure to ICIs was evaluated. For all types of cancer, median OS durations for the ICI and no-ICI cohorts were 14.0 and 7.9 months, respectively (HR: 0.88; 95% CI: 0.85-0.91). More specifically, OS was remarkably prolonged in patients with NSCLC (14.4 vs. 8.2 months; HR: 0.86; 95% CI: 0.82-0.90), TNBC (23.9 vs. 11.6 months; HR: 0.87; 95% CI: 0.82-0.92), and melanoma (27.6 vs. 16.8 months; HR: 0.80; 95% CI: 0.73-0.88) if patients had exposure to ICIs. In contrast, there was no significant difference in OS of patients with RCC treated with and without ICIs (16.7 vs. 14.0 months; HR: 0.96; 95% CI: 0.86-1.10).
Conclusions:
Overall, BM indicates poor patient outcome. Treatment with ICIs improves survival of patients with NSCLC, TNBC, and melanoma and BM; however, no significant improvement was observed in RCC. Investigations to identify prognostic features, oncogenomic profiles, and predictive biomarkers are warranted.
Insights
Immune checkpoint inhibitors (ICIs) significantly improve survival for patients with brain metastases (BM) from non-small cell lung cancer, triple-negative breast cancer, and melanoma. However, ICIs did not show a survival benefit for renal cell carcinoma with BM.
Area of Science:
- Oncology
- Immunotherapy
- Clinical Research
Background:
- Brain metastases (BM) present a poor prognosis with limited effective systemic therapies.
- Real-world data on the efficacy of immune checkpoint inhibitors (ICIs) in diverse BM populations are crucial.
Purpose of the Study:
- To evaluate the clinicopathological features of patients with BM from various solid tumors.
- To assess the impact of ICI therapy on overall survival (OS) in patients with BM.
Main Methods:
- Retrieved deidentified data from the TriNetX real-world database for 227,255 patients with BM.
- Utilized Kaplan-Meier plots and log-rank tests to compare survival outcomes between cohorts with and without ICI exposure.
- Calculated hazard ratios (HR) and 95% confidence intervals (CI) to quantify treatment effects.
Main Results:
- Median OS from initial diagnosis was 12.3 months, and from BM development was 7.1 months.
- ICI therapy significantly prolonged OS in patients with BM from non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), and melanoma (median OS: 14.0 months with ICIs vs. 7.9 months without).
- No significant OS improvement was observed in patients with renal cell carcinoma (RCC) and BM treated with ICIs (16.7 months vs. 14.0 months).
Conclusions:
- BM is associated with poor outcomes, but ICI therapy offers a survival benefit for specific cancer types.
- ICI therapy demonstrates efficacy in improving survival for NSCLC, TNBC, and melanoma with BM.
- Further research is needed to identify prognostic features and predictive biomarkers for ICI response in BM.
