Clinical and molecular correlates of PD-L1 expression in patients with lung adenocarcinomas Journal Article
| Authors: | Schoenfeld, A. J.; Rizvi, H.; Bandlamudi, C.; Sauter, J. L.; Travis, W. D.; Rekhtman, N.; Plodkowski, A. J.; Perez-Johnston, R.; Sawan, P.; Beras, A.; Egger, J. V.; Ladanyi, M.; Arbour, K. C.; Rudin, C. M.; Riely, G. J.; Taylor, B. S.; Donoghue, M. T. A.; Hellmann, M. D. |
| Article Title: | Clinical and molecular correlates of PD-L1 expression in patients with lung adenocarcinomas |
| Abstract: | Background: Programmed death-ligand 1 (PD-L1) expression is the only FDA-approved biomarker for immune checkpoint inhibitors (ICIs) in patients with lung adenocarcinoma, but sensitivity is modest. Understanding the impact of molecular phenotype, clinical characteristics, and tumor features on PD-L1 expression is largely unknown and may improve prediction of response to ICI. Patients and methods: We evaluated patients with lung adenocarcinoma for whom PD-L1 testing and targeted next-generation sequencing (using MSK-IMPACT) was performed on the same tissue sample. Clinical and molecular features were compared across PD-L1 subgroups to examine how molecular phenotype associated with tumor PD-L1 expression. In patients treated with anti-PD-(L)1 blockade, we assessed how these interactions impacted efficacy. Results: A total of 1586 patients with lung adenocarcinoma had paired PD-L1 testing and targeted next-generation sequencing. PD-L1 negativity was more common in primary compared to metastatic samples (P < 0.001). The distribution of PD-L1 expression (lymph nodes enriched for PD-L1 high; bones predominantly PD-L1 negative) and predictiveness of PD-L1 expression on ICI response varied by organ. Mutations in KRAS, TP53, and MET significantly associated with PD-L1 high expression (each P < 0.001, Q < 0.001) and EGFR and STK11 mutations associated with PD-L1 negativity (P < 0.001, Q = 0.01; P = 0.001, Q < 0.001, respectively). WNT pathway alterations also associated with PD-L1 negativity (P = 0.005). EGFR and STK11 mutants abrogated the predictive value of PD-L1 expression on ICI response. Conclusion: PD-L1 expression and association with ICI response vary across tissue sample sites. Specific molecular features are associated with differential expression of PD-L1 and may impact the predictive capacity of PD-L1 for response to ICIs. © 2020 European Society for Medical Oncology |
| Keywords: | adult; controlled study; protein expression; aged; primary tumor; gene mutation; major clinical study; cancer patient; phenotype; vasculotropin receptor; metastasis; cohort analysis; tumor marker; tumor suppressor gene; lung adenocarcinoma; immunotherapy; lymph node; bone; egfr gene; oncogene k ras; wnt protein; predictive value; scatter factor receptor; pd-1; programmed death 1 ligand 1; nsclc; wnt signaling; pd-l1; protein kinase lkb1; met gene; cancer prognosis; high throughput sequencing; human; male; female; priority journal; article; stk11 gene |
| Journal Title: | Annals of Oncology |
| Volume: | 31 |
| Issue: | 5 |
| ISSN: | 0923-7534 |
| Publisher: | Oxford University Press |
| Date Published: | 2020-05-01 |
| Start Page: | 599 |
| End Page: | 608 |
| Language: | English |
| DOI: | 10.1016/j.annonc.2020.01.065 |
| PUBMED: | 32178965 |
| PROVIDER: | scopus |
| PMCID: | PMC7523592 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work