Safety and efficacy analyses of atezolizumab in advanced non-small cell lung cancer (NSCLC) patients with or without baseline brain metastases

Abstract

Background: 20%-40% patients (pts) with advanced NSCLC develop brain metasta-ses (mets), which are associated with poor survival. Atezolizumab (atezo; anti-PD-L1) monotherapy has shown clinical benefit in pts with NSCLC regardless of PD-L1 expression status. Here we compare the safety and efficacy of atezo in NSCLC pts with or without baseline brain mets. Methods: Safety analyses were conducted on pts who received atezo as 2Lþ treatment in 5 studies: PCD4989g, BIRCH, FIR, POPLAR and OAK. Pts had previously treated stable/asymptomatic or no brain mets at baseline. Efficacy analyses were conducted on pts in the atezo and docetaxel (doc) arms of OAK. Results: The pooled safety cohort included 1452 pts; 79 (5%) had brain mets. The incidence of all AEs and SAEs was similar in pts with or without brain mets (Table). A numerically higher rate of neurological AEs and SAEs was reported in pts with vs those without brain mets. No treatment-related G4-5 neurological AEs or SAEs were seen in pts with brain mets. The most common treatment-related neurological AE was headache in 6 (8%) pts with and 42 (3%) pts without brain mets. Efficacy cohort included the first 850 pts with or without brain mets from OAK who were randomized to atezo or doc. Atezo showed survival benefit vs doc in pts with brain mets (HR ¼ 0.54, 95% CI: 0.31, 0.94; mOS 20.1 mo [n ¼ 38] vs 11.9 mo [n ¼ 47] with atezo vs doc) as well as in pts without brain mets (HR ¼ 0.75, 95% CI: 0.63, 0.89; mOS 13.0 mo [n ¼ 387] vs 9.4 mo [n ¼ 378] with atezo vs doc). The risk of developing new CNS lesions appeared to be lower with atezo vs doc (HR ¼ 0.42, 95% CI: 0.15, 1.18; median time to develop new CNS lesion, not reached vs 9.5 mo) in pts with baseline brain mets. Conclusions: Atezo demonstrated an acceptable safety profile and encouraging survival benefit in pts with NSCLC who had previously treated stable/asymptomatic brain mets. Results of this analyses warrant further investigation of atezo in advanced NSCLC pts with CNS mets. Background: Anti-PD-1/PD-L1 therapies have demonstrated meaningful clinical benefit in pts with EGFR/ALK wild-type (WT) advanced NSCLC. However, to our knowledge these agents have never been investigated in a study prospectively focusing on NSCLC pts with EGFR mutations or ALK alterations (EGFRmut/ALKþ), a distinct subgroup with clear biological and treatment outcome differences compared with EGFR/ALK WT pts. Durvalumab is an engineered human IgG1 mAb targeting PD-L1. Methods: ATLANTIC (NCT02087423) was a Phase 2, open-label, single-arm trial in pts with locally advanced or metastatic Stage IIIB-IV NSCLC (WHO PS 0 or 1; 2 prior systemic regimens, including 1 platinum-based and 1 TKI [EGFRmut/ALKþ pts]). There was no maximum number of prior treatments. The study initially enrolled all-comers and then was restricted to pts with PD-L1 high tumours (25% of tumour cells with membrane staining). The study included 3 pt cohorts defined by EGFR/ALK status and tumor PD-L1 expression; here we report results from EGFRmut/ALKþ pts (Cohort 1). The primary outcome was ORR (RECIST v1.1). Secondary outcomes included DCR, DoR, PFS, OS, and safety (CTCAE v4.03). Results: As of 3 June 2016, 111 pts (median age 61 years, 63% female, 59% WHO PS 1, 99% non-squamous histology; 59% never smokers; mean prior therapies 3.8) had received durvalumab (10 mg/kg i.v. q2w for 12 months). Responses were durable. Most AEs were low grade. Immune-mediated AEs were manageable with standard treatment guidelines; 5.4% of pts had Grade 3 treatment-related (TR) AEs and 0.9% had TRAEs leading to discontinuation.