Efficacy and safety of upfront radiotherapy with immune checkpoint inhibitors for brain metastasis in non-small cell lung cancer

Introduction

The optimal timing of radiotherapy (RT) for asymptomatic brain metastasis (aBM) in patients with non-small cell lung cancer (NSCLC) without targetable oncogenic drivers treated with immune checkpoint inhibitors (ICIs) remains unclear. This study aimed to assess the efficacy and safety of upfront (U)-RT combined with ICIs for aBM.

Methods

We retrospectively reviewed consecutive patients with aBM from NSCLC who received ICI-containing chemotherapy at National Cancer Center Hospital East between 2016 and 2021. The U-RT group was defined patients who received RT for aBM before or during the first ICI cycle, and the non-U-RT group otherwise.

Results

Of the 324 patients with NSCLC and aBM screened, 54 were enrolled, with 34 and 20 patients in the U-RT and non-U-RT groups, respectively. The median overall survival was 27.5 and 13.8 months (hazard ratio [HR] = 0.40, 95 % confidence interval [CI] 0.19–0.87), respectively, and median cranial progression-free survival was 9.2 and 6.0 months (HR = 0.50, 95 % CI 0.25–0.98), respectively, in the U-RT and non-U-RT groups. The U-RT group showed a significantly lower aBM progression rate than the non-U-RT group (P = 0.04). U-RT was an independent prognostic factor in the multivariate analysis using propensity score adjustment (HR = 0.42, 95 % CI 0.18–0.96). Although severe adverse events were observed in 47 % and 35 % of patients in the U-RT and non-U-RT groups, respectively, no treatment-related deaths occurred.

Conclusions

ICIs with U-RT demonstrated higher efficacy with acceptable tolerability for aBM than ICIs without U-RT. Our findings should be confirmed in future prospective trials.