Tumor characteristics associated with benefit from pembrolizumab in advanced non–small cell lung cancer Journal Article
| Authors: | Hu-Lieskovan, S.; Lisberg, A.; Zaretsky, J. M.; Grogan, T. R.; Rizvi, H.; Wells, D. K.; Carroll, J.; Cummings, A.; Madrigal, J.; Jones, B.; Gukasyan, J.; Shintaku, I. P.; Slamon, D.; Dubinett, S.; Goldman, J. W.; Elashoff, D.; Hellmann, M. D.; Ribas, A.; Garon, E. B. |
| Article Title: | Tumor characteristics associated with benefit from pembrolizumab in advanced non–small cell lung cancer |
| Abstract: | Purpose: Several biomarkers have been individually associated with response to PD-1 blockade, including PD-L1 and tumor mutational burden (TMB) in non–small cell lung cancer (NSCLC), and CD8 cells in melanoma. We sought to examine the relationship between these distinct variables with response to PD-1 blockade and long-term benefit. Experimental Design: We assessed the association between baseline tumor characteristics (TMB, PD-L1, CD4, and CD8) and clinical features and outcome in 38 patients with advanced NSCLC treated with pembrolizumab (median follow-up of 4.5 years, range 3.8–5.5 years). Results: PD-L1 expression and CD8 infiltration correlated with each other and each significantly associated with objective response rate (ORR) and progression-free survival (PFS). TMB was independent of PD-L1 and CD8 expression, and trended towards association with ORR and PFS. There was no association between CD4 infiltration and outcomes. Only PD-L1 expression was correlated with overall survival (OS). Among 5 patients with long-term survival >3 years with no additional systemic therapy, PD-L1 expression was the only discriminating feature. The increased predictive value for PFS and OS of composite biomarker inclusive of PD-L1, CD8, CD4, and TMB was limited. Conclusions: In patients with NSCLC treated with PD-1 blockade with long-term follow up, TMB, PD-L1, and CD8 were each associated with benefit from PD-1 blockade. Pretreatment PD-L1 expression was correlated with T lymphocyte infiltration and OS, whereas models incorporating TMB and infiltrating CD4 and CD8 lymphocytes did not substantially add to the predictive value of PD-L1 alone for OS. © 2019 American Association for Cancer Research. |
| Journal Title: | Clinical Cancer Research |
| Volume: | 25 |
| Issue: | 16 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2019-08-15 |
| Start Page: | 5061 |
| End Page: | 5068 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-18-4275 |
| PUBMED: | 31113840 |
| PROVIDER: | scopus |
| PMCID: | PMC6901027 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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