538P Single-center retrospective analysis of patients with brain metastases included in early phase clinical trials

Historically patients (pts) with brain metastases (BM) were excluded from early phase clinical trials due to concerns over prognosis, risk of toxicity or lack of brain penetrance. Recent trials allow the inclusion of pts with stable (asymptomatic and/or treated) BM, as recommended by the ASCO and Friends of Cancer Research Brain Metastases Working Group. We aimed to describe the outcomes of patients with BM enrolled in early phase clinical trials. Retrospective cohort analysis of clinical and treatment (trt) response data of pts included in early phase clinical trials at Vall d'Hebron Institute of Oncology between January 2012 and April 2023. Objective response rate (ORR) and disease control rate (DCR) were calculated. Median progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, survival between groups was compared using log-rank test and cox regression. A total of 815 pts treated at our center were analyzed; 51 pts had stable BM at inclusion, 28 (54.9%) male and 23 (45.1%) female. Most frequent types: lung (51.0%), melanoma/skin (23.5%). Forty-one pts (80.4%) received prior brain trt: 37 radiotherapy, 3 surgery and 1 both. Ten pts (19.6%) were included with asymptomatic untreated BM. Type of experimental trt: immunotherapy 72.5%, targeted therapy 21.6%, antibody-drug conjugates 5.9%. Phase of clinical trial in which pts were included: phase 1 dose escalation 23.5%, phase 1 expansion cohorts 70.6%, and phase 2 basket studies 5.6%. Median OS in pts without BM was comparable to those with: 9.1 months vs 6.3 (p=not significant); median PFS was superior in BM pts: 1.8 vs 2.6 (HR 0.52, p<0.0001). The rate of OS<3 months was 31.4% in BM pts and 33.3% had PFS>4 months. ORR and DCR were respectively 19.6% and 54.9%, intracranial ORR and DCR were 7.8% and 72.7%. Only 4 pts discontinued treatment due to isolated intracranial progression (iPD), and 2 had iPD as best response. There were no statistically significant differences in PFS and OS of pts with treated BM and asymptomatic untreated BM. The trt response and survival data for pts with BM in our cohort support the recommendations of ASCO and Friends of Cancer Research on the inclusion of pts with BM in clinical trials.