8077 Background: Sunitinib (SU), an oral, multitargeted inhibitor of VEGFRs, PDGFRs, KIT, FLT3, CSF-1R, and RET has promising single-agent antitumor activity in refractory non-small cell lung cancer (NSCLC) (Socinski JCO 2008). Brain metastases (BrMs) occur in ≥25% of NSCLC patients (pts); preclinical data suggest that VEGF signaling is required for the growth of BrMs, and that SU can cross the blood-brain barrier. This study assessed the safety and preliminary efficacy of SU in NSCLC pts with BrMs. Methods: NSCLC pts who had received ≤2 prior systemic therapies and prior whole brain radiation therapy (WBRT) were eligible to receive SU at a starting dose of 37.5 mg with continuous daily dosing (CDD) in 4-wk cycles. Antitumor efficacy was based on overall (RECIST) and intracranial (WHO) tumor assessments. Intracranial disease was assessed by MRI. Safety was assessed by monitoring adverse events (AEs) and health-related quality of life was assessed using FACT/NCCN Lung Symptom Index (FLSI) and Brain Symptom Index (FBrSI). Study termination was to occur when 3 cases of intracranial hemorrhage (ICH) associated with neurologic deficit were noted. Results: To date, 47 pts, including 28 with adenocarcinoma and 10 with squamous cell carcinoma, received SU for a median of 2 cycles (range: 1, 9). The median age of pts was 61 yrs (range: 35, 75), most were male (n=26, 55%), were ever smokers (n=36, 77%) and all had good performance status (ECOG 0/1). In total, 25 pts (53%) experienced non-neurologic grade (G) 3/4 AEs; the most frequent were fatigue/asthenia and dyspnea. Neurologic AEs occurred in 4 pts (9%), including intracranial pressure increased, mental impairment, and gait disturbance (each n=1 and G1) and 1 pt with G3 convulsion and peripheral motor neuropathy. Importantly, no cases of ICH were noted. Stable disease occurred in 7 (19%) of 36 measurable pts. Median PFS was 10.9 wks (95% CI: 6.4,15.4). Median OS was 19.6 wks (95% CI:13.1, NR). Mean change from baseline in FLSI and FBrSI scores did not differ significantly at any time point. Conclusions: Oral SU 37.5 mg on a CDD schedule had a manageable safety profile in NSCLC pts with BrMs. These data support the investigation of SU in combination with agents with known antitumor activity in pts with BrMs. [Table: see text]
Chemotherapeutic Agents for Brain Metastases in Non-Small Cell Lung Cancer: A Case Report with Eribulin Mesylate and Review of the Literature