MMOD-14 IMPACT OF SYSTEMIC THERAPY ACTIVITY ON BRAIN METASTASIS OUTCOMES IN A FEMALE AND HISPANIC-DOMINANT LUNG CANCER COHORT TREATED WITH STEREOTACTIC RADIOSURGERY

We analyzed the impact of systemic therapy on lung cancer (LC) patients treated with stereotactic radiosurgery (SRS) for brain metastasis (BM) in terms of objective response, intracranial progression-free survival (iPFS), and overall survival (OS). Response was calculated using chi-square analysis with adjusted residuals, while iPFS and OS were computed using the Kaplan-Meier method. A total of 426 BMs in 91 LC patients from 01/2017-07/2022 were included. The median age was 66 years (interquartile range [IQR] 58-73), in our predominantly female (57.1%) and Hispanic (76.9%) population. The median number of BMs was 4 (IQR: 2-8). Systemic therapy was grouped as no switch (no change; 15 patients, 34 BMs) or switch (change from pre- to post-SRS), with the latter classified as a switch-up (increased CNS activity; 76 patients, 392 BMs) or switch-down (decreased CNS activity; 0 patients). At first radiographic evaluation, rates of complete response, partial response, stable disease, or progressive disease were similar (switch-up [%]/no switch [%]) in 32.7%/50.0%, 23.0%/11.8%, 38.3%/32.4%, and 6.1%/5.9%, p<0.05). With a median follow-up of 18 months (IQR: 5-28), the estimated iPFS (95% CI) for the switch-up group was 7.0 months (4.5-9.5), and the no switch group was 10.0 months (2.5-17.5) (p=0.37). However, the estimated OS for the switch-up group was 21.0 months (18.5-23.5) vs. 19.0 months (15.0-23.0), for no switch (p=0.04). Multivariate analysis identified KPS, lesion number, burden of disease, and prescription dose as predictors for iPFS, and age, lesion number, KPS, and disease status (p<0.05) for OS. In conclusion, upgrading systemic therapy based on intracranial activity combined with SRS for BMs from LC is associated with a statistically significant improvement in OS, without impacting iPFS or first response, implying considerable potential for developing next-generation agents with better intracranial activity.