Real-world outcomes and clinical characteristics of patients with brain metastases from EGFR mutated non-small cell lung cancer: Data from a large retrospective study (REFLECT).
Authors: Janzic Urska , Addeo Alfredo , Dudnik Elizabeth , Charpidou Andriani , Pluzanski Adam , Ciuleanu Tudor-Eliade , Donev Ivan , Rigney Una , Elbaz Judith , Aaroe Jorgen , Peled Nir , Hochmair Maximilian 
Published: June 2021

9086 Background: Brain metastases (BM) frequently occur in patients (pts) with epidermal growth factor receptor mutated non-small cell lung cancer (EGFRm NSCLC) and represent a poor prognostic marker. This study aimed to describe the clinical characteristics, treatment patterns and survival outcomes in EGFRm NSCLC pts treated with 1st or 2nd generation tyrosine-kinases inhibitors (TKIs) in first-line (1L). Methods: The retrospective real-world study REFLECT (NCT04031898) collected data from 896 pts initiating 1L TKI between 1 January 2015-30 June 2018 in Europe and Israel. Descriptive statistics were used to assess demographic and clinical characteristics in subgroups of patients with and without BM. Kaplan-Meier methods were used to estimate median real world progression free survival (mPFS) and overall survival (mOS) from start of 1L. Results: Out of 896 pts, 198 (22.1%) had BM at start of 1L, 134 (15%) developed BM later (any time), and 564 (62.9%) had no sign of BM at the time of data collection. Among pts who later developed BM the median time between the start of 1L and first diagnosis of BM was 13.5 months. Median duration of follow-up was 21.5 months. Of 332 pts with BM at any time 64.2% were female, similar to the ratio in pts without BM (64.0%). At diagnosis, median age was 65 years in pts with BM vs. 70 in those who never developed BM. Of pts with BM at any time, 50.9% had exon 19 deletion, 30.4% L858R point mutation and 18.7 % uncommon EGFR mutations at baseline, compared to 56.6%, 31.7% and 11.7% in pts without BM, respectively. At data collection, 94.9% of the pts with BM at diagnosis had progressed compared to 79.8% among those with no BM. Overall, whole brain radiation was the most frequently used treatment for BM (31.0%) followed by stereotactic radiosurgery (18.1%) and targeted therapies (13.3%). T790M testing rates were highest among pts developing BM later (85.7%) and lowest among those with BM from start (66.1%). The T790M positivity rate was highest in pts developing BM later (65.7%) and lowest among those with BM from start (50.4%). More pts received osimertinib in later lines among those with BM at any time compared to those without BM (51.3% vs 43.8%). Median real world PFS and OS (95% CI) were shorter among pts with BM at baseline compared to those never developing BM: 10.2 (8.8, 11.5) vs 15.2 (13.7, 16.1) months, and 19.4 (17.1, 22.1) vs 30.3 (27.1, 33.8) months, respectively. At the time of data collection, 77.3% of pts with BM at baseline were deceased compared to 52.5% pts with no BM. Conclusions: More than one third of pts included in REFLECT had BM at any time. Uncommon EGFR variants at baseline were observed more frequently in pts with BM. mPFS and mOS were shorter in pts with BM at baseline compared to those never developing BM. These data highlight the need for improved treatment and CNS control in pts with EGFRm NSCLC. Clinical trial information: NCT04031898.