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Your search keyword '"Stanley I. Gutiontov"' showing total 2 results
Start Over Author "Stanley I. Gutiontov" Journal scientific reports
2 results on '"Stanley I. Gutiontov"'

1. CDKN2A loss-of-function predicts immunotherapy resistance in non-small cell lung cancer

Author

Stanley I. Gutiontov, William Tyler Turchan, Liam F. Spurr, Sherin J. Rouhani, Carolina Soto Chervin, George Steinhardt, Angela M. Lager, Pankhuri Wanjari, Renuka Malik, Philip P. Connell, Steven J. Chmura, Aditya Juloori, Philip C. Hoffman, Mark K. Ferguson, Jessica S. Donington, Jyoti D. Patel, Everett E. Vokes, Ralph R. Weichselbaum, Christine M. Bestvina, Jeremy P. Segal, and Sean P. Pitroda

Subjects
Medicine, Science
Abstract

Abstract Immune checkpoint blockade (ICB) improves outcomes in non-small cell lung cancer (NSCLC) though most patients progress. There are limited data regarding molecular predictors of progression. In particular, there is controversy regarding the role of CDKN2A loss-of-function (LOF) in ICB resistance. We analyzed 139 consecutive patients with advanced NSCLC who underwent NGS prior to ICB initiation to explore the association of CDKN2A LOF with clinical outcomes. 73% were PD-L1 positive (≥ 1%). 48% exhibited high TMB (≥ 10 mutations/megabase). CDKN2A LOF was present in 26% of patients and was associated with inferior PFS (multivariate hazard ratio [MVA-HR] 1.66, 95% CI 1.02–2.63, p = 0.041) and OS (MVA-HR 2.08, 95% CI 1.21–3.49, p = 0.0087) when compared to wild-type (WT) patients. These findings held in patients with high TMB (median OS, LOF vs. WT 10.5 vs. 22.3 months; p = 0.069) and PD-L1 ≥ 50% (median OS, LOF vs. WT 11.1 vs. 24.2 months; p = 0.020), as well as in an independent dataset. CDKN2A LOF vs. WT tumors were twice as likely to experience disease progression following ICB (46% vs. 21%; p = 0.021). CDKN2A LOF negatively impacts clinical outcomes in advanced NSCLC treated with ICB, even in high PD-L1 and high TMB tumors. This novel finding should be prospectively validated and presents a potential therapeutic target.

Published
2021
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2. CDKN2A loss-of-function predicts immunotherapy resistance in non-small cell lung cancer

Author

Mark K. Ferguson, William Tyler Turchan, Sean P. Pitroda, Jessica S. Donington, Jyoti D. Patel, Renuka Malik, Sherin J. Rouhani, Steven J. Chmura, Christine M. Bestvina, Philip C. Hoffman, Angela M. Lager, Philip P. Connell, Carolina Soto Chervin, Aditya Juloori, George Steinhardt, Ralph R. Weichselbaum, Everett E. Vokes, Pankhuri Wanjari, Stanley I. Gutiontov, Jeremy P. Segal, and Liam F. Spurr

Subjects
Oncology, Adult, Male, medicine.medical_specialty, Lung Neoplasms, medicine.medical_treatment, Science, Article, CDKN2A Loss, CDKN2A, Loss of Function Mutation, Internal medicine, Carcinoma, Non-Small-Cell Lung, medicine, Biomarkers, Tumor, Cancer genomics, Humans, Lung cancer, Cyclin-Dependent Kinase Inhibitor p16, Aged, Retrospective Studies, Aged, 80 and over, Multidisciplinary, business.industry, Hazard ratio, Immunotherapy, Middle Aged, medicine.disease, Prognosis, Immune checkpoint, Blockade, Survival Rate, Drug Resistance, Neoplasm, Medicine, Female, Non small cell, business, Non-small-cell lung cancer, Follow-Up Studies
Abstract

Immune checkpoint blockade (ICB) improves outcomes in non-small cell lung cancer (NSCLC) though most patients progress. There are limited data regarding molecular predictors of progression. In particular, there is controversy regarding the role of CDKN2A loss-of-function (LOF) in ICB resistance. We analyzed 139 consecutive patients with advanced NSCLC who underwent NGS prior to ICB initiation to explore the association of CDKN2A LOF with clinical outcomes. 73% were PD-L1 positive (≥ 1%). 48% exhibited high TMB (≥ 10 mutations/megabase). CDKN2A LOF was present in 26% of patients and was associated with inferior PFS (multivariate hazard ratio [MVA-HR] 1.66, 95% CI 1.02–2.63, p = 0.041) and OS (MVA-HR 2.08, 95% CI 1.21–3.49, p = 0.0087) when compared to wild-type (WT) patients. These findings held in patients with high TMB (median OS, LOF vs. WT 10.5 vs. 22.3 months; p = 0.069) and PD-L1 ≥ 50% (median OS, LOF vs. WT 11.1 vs. 24.2 months; p = 0.020), as well as in an independent dataset. CDKN2A LOF vs. WT tumors were twice as likely to experience disease progression following ICB (46% vs. 21%; p = 0.021). CDKN2A LOF negatively impacts clinical outcomes in advanced NSCLC treated with ICB, even in high PD-L1 and high TMB tumors. This novel finding should be prospectively validated and presents a potential therapeutic target.

Published
2021

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