81O - Safety and efficacy analyses of atezolizumab in advanced non-small cell lung cancer (NSCLC) patients with or without baseline brain metastases

Date 07 May 2017
Event ELCC 2017
Session ESMO-IASLC Best Abstracts
Topics Non-Small-Cell Lung Cancer, Locally Advanced
Non-Small-Cell Lung Cancer, Metastatic
Cancer Immunology and Immunotherapy
Lung and other Thoracic Tumours
Presenter Rimas Lukas
Citation Annals of Oncology (2017) 28 (suppl_2): ii28-ii51. 10.1093/annonc/mdx091
Authors R.V. Lukas1, M. Gandhi2, C. O’hear2, S. Hu2, C. Lai2, J.D. Patel3
  • 1Department Of Neurology And Section Of Hematology & Oncology, University of Chicago, 60637 - Chicago/US
  • 2Genentech, Inc., South San Francisco/US
  • 3Section Of Hematology/oncology, University of Chicago, Chicago/US

Abstract

Background

≈ 20%-40% patients (pts) with advanced NSCLC develop brain metastases (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 2L+ 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 = 0.54, 95% CI: 0.31, 0.94; mOS 20.1 mo [n = 38] vs 11.9 mo [n = 47] with atezo vs doc) as well as in pts without brain mets (HR = 0.75, 95% CI: 0.63, 0.89; mOS 13.0 mo [n = 387] vs 9.4 mo [n = 378] with atezo vs doc). The risk of developing new CNS lesions appeared to be lower with atezo vs doc (HR = 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.rnTable: 81O

Summary of safety data in advanced NSCLC patients with and without baseline brain metastases following atezolizumab as 2L+ treatment

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SafetyPooled cohorta (N = 1452)
Patients with baseline brain mets (n = 79) n (%)patients without baseline brain mets (n = 1373) n (%)
Any AE75 (95%)1261 (92%)
Any neurological AE37 (47%)414 (30%)
Treatment-related AEs55 (70%)876 (64%)
Treatment-related neurological AEs14 (18%)128 (9%)
Any SAE26 (33%)492 (36%)
Any neurological SAEs5 (6%)36 (3%)
Treatment-related SAEs7 (9%)135 (10%)
Treatment-related neurological SAEs07 (0.5%)
Discontinued treatment due to AE8 (10%)99 (7%)
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From PCD4989g (NCT01375842), BIRCH (NCT02031458), FIR (NCT01846416), POPLAR (NCT01903993) and OAK (NCT02008227) trials.

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Clinical trial identification

NCT01375842, NCT02031458, NCT01846416, NCT01903993, NCT02008227

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd/Genentech Inc., a member of the Roche Group

Funding

F. Hoffmann-La Roche Ltd/Genentech Inc., a member of the Roche Group

Disclosure

R.V. Lukas: Advisory board (2016) for Astra-Zeneca and advisory Board (2013) for Novocure. M. Gandhi: Genentech employee. C. O’Hear: Employee of Genentech and have stock in Roche. S. Hu: Employee and stockholder in Roche. C. Lai: Employee of and have stock in Roche. All other authors have declared no conflicts of interest.