Abstract 3697: High PD-L1 expression and targetable mutations occur independently in NSCLC and are not influenced by smoking or race
Authors: Choudhury Noura J. , Eghtesad Mansooreh , Cursio John , Kadri Sabah , Ritterhouse Lauren , Segal Jeremy , Husain Aliya , Patel Jyoti D. 
Published: August 2018

Background: Targeted therapies such as EGFR tyrosine kinase inhibitors (TKIs), and immunotherapy (IO) with PD-L1 inhibitors have revolutionized first-line treatment options for advanced non-small cell lung cancer (NSCLC). Several small studies suggest that high PD-L1 expression rarely overlaps with classic driver mutations, yet it remains unclear how smoking history, race, and stage may influence the interaction between PD-L1 expression and targetable driver mutations. In our racially diverse population with a high proportion of African American patients, we investigated whether high PD-L1 expression occurs concurrently with targetable mutations in EGFR, BRAF, and MET and whether smoking history, stage, or race alters this distribution.

Methods: In this retrospective study, we selected all NSCLC patients of any stage at our institution whose tumor samples had undergone both in-house next-generation sequencing (NGS) and PD-L1 staining with the Dako Clone 28.8 antibody between March 2016 to July 2017. Our validated NGS assay, the OncoPlus, detects mutations, deletions, and insertions in 147 clinically reported genes, including all classic driver mutations in lung cancer. Patient demographics, treatments and response data were extracted from the electronic medical record through October 1, 2017. We then used Wilson proportion test and chi-squared analysis to analyze whether PD-L1 expression and actionable mutations varied by race, smoking, age and stage.

Results: 114 cases had both PD-L1 staining and NGS analysis available. 71 (62.2%) patients had ≥10 pack year smoking history while 21 (18.4%) patients were never smokers. 41 (35.9%) patients were African American, 62 (54.4%) Caucasian and 7 (6.1%) were Asian. 26 (22.8%) had high expression of PD-L1 (≥50% cells staining positive), and 15 (13.2%), 1 (0.8%), 4 (3.5%), and 6 (5.2%) patients, respectively, had an EGFR, BRAF (V600E), ERBB2, and MET exon 14 skip mutation. 4/26 patients with high PD-L1 expression had a targetable mutation, compared to 22/88 patients with low PD-L1 expression (p&lt;0.001, Wilson test). This distribution did not vary significantly when stratified by race, stage, or smoking history.

Conclusions: We present here our institution's novel workflow of obtaining both in-house NGS and PD-L1 staining at time of initial biopsy, in a diverse population with 1/3 African American patients. We demonstrate that high PD-L1 expression and actionable driver mutations infrequently coexist in the same tumor, and this relationship is not driven by smoking, race, or stage. Our results strongly suggest the necessity of obtaining both PD-L1 staining and NGS at time of initial biopsy to identify optimal therapies for patients with advanced disease. Our results imply that patients with actionable driver mutations are unlikely to benefit from later treatment with IO, which we hope to test explicitly in future studies.

Citation Format: Noura J. Choudhury, Mansooreh Eghtesad, John Cursio, Sabah Kadri, Lauren Ritterhouse, Jeremy Segal, Aliya Husain, Jyoti D. Patel. High PD-L1 expression and targetable mutations occur independently in NSCLC and are not influenced by smoking or race [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3697.