Outcomes of Immune-Checkpoint Inhibitors (ICIs) and Stereotactic Radiosurgery (SRS) in Non-Small Cell Lung Cancer Brain Metastases (NSCLCBM) Patients

Abstract

<h3>Purpose/Objective(s)</h3> Non-small cell lung cancer (NSCLC) is the leading cause of brain metastases. Systemic therapies and radiation therapy are both potential treatment options for NSCLCBM patients. ICIs have been designated as a promising alternative in patients without targetable molecular alterations, while SRS has also grown into favor, as it is non-invasive and irradiates only the lesion. In our retrospective study, we evaluated overall survival (OS) and progression-free survival (PFS) between NSCLCBM patients who received ICIs, SRS, and a combination of both treatments. We hypothesize that the combination of ICIs and SRS will be associated with improved OS and PFS when compared to either treatment alone. <h3>Materials/Methods</h3> We investigated all NSCLCBM patients diagnosed between 2010 and 2019. Molecular marker status, types of therapies used, and dates of progression were collected. OS was defined as the start date of either type of therapy to the date of last follow-up or death. Most NSCLCBM patients who received SRS or ICIs therapies also received standard chemotherapy. The Cox proportional model was used to estimate OS and PFS. <h3>Results</h3> A total of 2989 NSCLCBM patients were analyzed. 286 patients received only ICIs, 916 received only SRS, and 469 were treated with both SRS and ICIs. The median OS (mOS) in patients treated with ICI was 17.2 months, while the mOS in patients treated with SRS or both ICI and SRS were 23.2 months (hazard ratio (HR) = 0.79 (95% confidence interval (CI) = 0.68, 0.92), <i>P</i>-value (<i>P</i>) < 0.002) and 48.2 months (HR = 0.45) (95% CI = 0.38, 0.54), <i>P</i> < 0.001), respectively. The median PFS (mPFS) in patients treated with ICIs, SRS, and both SRS and ICIs was 9.92 months, 23.25 months (HR = 0.56 (95% CI = 0.48, 0.64), <i>P</i> < 0.001), and 29.33 months (HR = 0.45 (95% CI = 0.39, 0.53), <i>P</i> < 0.001), respectively. <h3>Conclusion</h3> ICIs and SRS are both common therapies in the field of NSCLCBM. Our retrospective study data showed improved mOS and mPFS in patients who received SRS or the combination of SRS and ICIs when compared to those who received ICIs. Though there was longer mOS and mPFS in the combination group compared to the SRS group, the statistical significance has yet to be analyzed. However, our data is encouraging that there may be a synergistic survival benefit in the combination of SRS and ICIs cohort, which could be especially beneficial in patients with strong PDL1 expression.