P2.03b-014 Atezolizumab in Advanced NSCLC Patients with Baseline Brain Metastases: A Pooled Cohort Safety Analysis: Topic: Brain Meta

Abstract

Brain metastases, occurring in 20% to 40% of patients with advanced NSCLC, are associated with poor survival. Atezolizumab (anti-PDL1) inhibits PD-L1/PD-1 signaling and restores tumor-specific T-cell immunity. Clinical benefits have been observed in patients with NSCLC across PD-L1 expression levels following atezolizumab monotherapy, but the safety profile in NSCLC patients with brain metastases has not previously been explored. Pooled safety analyses were conducted in 843 patients who received atezolizumab as 2L+ treatment in 4 studies (PCD4989g: NCT01375842 [N = 76]; BIRCH: NCT02031458 [N = 520]; FIR: NCT01846416 [N = 105]; POPLAR: NCT01903993 [N = 142]). Patients had asymptomatic untreated brain metastases or stable previously treated brain metastases at baseline. 27 (3%) of 843 patients in the pooled cohort had baseline brain metastases; 23 of whom were previously treated with radiation to the brain. Among the 27 patients, mean age was 60 years, 41% were male, 85% had non-squamous NSCLC, and 70% had received 3L+ therapy. Median number of atezolizumab cycles (21d/cycle) was 4 (range, 1-39). Neurological AEs occurred in 12 (44%) patients with and 229 (28%) patients without baseline brain metastases (Table). The incidence of treatment-related neurological AEs was 4 (15%) in patients with and 77 (9%) in patients without baseline brain metastases, including the most common treatment-related AE of headache in 2 (7%) and 27 (3%) patients, respectively. The most common all-cause AEs in patients with baseline brain metastases were fatigue, nausea, and vomiting (7 [26%] each); 3 (11%) patients developed new brain lesions on study, none during treatment. No treatment discontinuations occurred due to AEs. The current analyses indicate that atezolizumab has an acceptable safety profile in patients with NSCLC who have asymptomatic or previously treated stable brain metastases. Further investigation is needed to fully assess the efficacy of atezolizumab in this patient population.Tabled 1Summary of safety data in patients with advanced NSCLC with and without baseline brain metastases following atezolizumab as 2L+ treatmentPooled Cohort (N = 843)Patients Without Baseline Brain Metastases (n = 816) n (%)Patients With Baseline Brain Metastases (n = 27) n (%)Any AE779 (96%)26 (96%)Any neurological AE229 (28%)12 (44%)Treatment-related AEs548 (67%)16 (59%)Treatment-related neurological AEs77 (9%)4 (15%)Serious AE311 (38%)9 (33%)Serious neurological AEs21 (3%)1 (4%)Treatment-related SAEs78 (10%)1 (4%)Discontinued treatment due to AE47 (6%)0 (0%) Open table in a new tab