Effects of Co-occurring Genomic Alterations on Outcomes in Patients with KRAS-Mutant Non-Small Cell Lung Cancer

Publication Date:
2018-01-17
Publisher:
The American Association for Cancer Research (AACR)
Print ISSN:
1078-0432
Electronic ISSN:
1557-3265
Topics:
Medicine
Published by:
http://www.aacr.org/
_version_ 1836398751801933825
autor Arbour, K. C., Jordan, E., Kim, H. R., Dienstag, J., Yu, H. A., Sanchez-Vega, F., Lito, P., Berger, M., Solit, D. B., Hellmann, M., Kris, M. G., Rudin, C. M., Ni, A., Arcila, M., Ladanyi, M., Riely, G. J.
beschreibung Purpose: KRAS mutations occur in approximately 25% of patients with non–small cell lung cancer (NSCLC). Despite the uniform presence of KRAS mutations, patients with KRAS -mutant NSCLC can have a heterogeneous clinical course. As the pattern of co-occurring mutations may describe different biological subsets of patients with KRAS -mutant lung adenocarcinoma, we explored the effects of co-occurring mutations on patient outcomes and response to therapy. Experimental Design: We identified patients with advanced KRAS -mutant NSCLC and evaluated the most common co-occurring genomic alterations. Multivariate analyses were performed incorporating the most frequent co-mutations and clinical characteristics to evaluate association with overall survival as well as response to platinum–pemetrexed chemotherapy and immune checkpoint inhibitors. Results: Among 330 patients with advanced KRAS -mutant lung cancers, the most frequent co-mutations were found in TP53 (42%), STK11 (29%), and KEAP1 / NFE2L2 (27%). In a multivariate analysis, there was a significantly shorter survival in patients with co-mutations in KEAP1 / NFE2L2 [HR, 1.96; 95% confidence interval (CI), 1.33–2.92; P ≤ 0.001]. STK11 (HR, 1.3; P = 0.22) and TP53 (HR 1.11, P = 0.58) co-mutation statuses were not associated with survival. Co-mutation in KEAP1 / NFE2L2 was also associated with shorter duration of initial chemotherapy (HR, 1.64; 95% CI, 1.04–2.59; P = 0.03) and shorter overall survival from initiation of immune therapy (HR, 3.54; 95% CI, 1.55–8.11; P = 0.003). Conclusions: Among people with KRAS -mutant advanced NSCLC, TP53, STK11 , and KEAP1 / NFE2L2 are the most commonly co-occurring somatic genomic alterations. Co-mutation of KRAS and KEAP1 / NFE2L2 is an independent prognostic factor, predicting shorter survival, duration of response to initial platinum-based chemotherapy, and survival from the start of immune therapy. Clin Cancer Res; 24(2); 334–40. ©2017 AACR .
citation_standardnr 6139898
datenlieferant ipn_articles
feed_id 9363
feed_publisher The American Association for Cancer Research (AACR)
feed_publisher_url http://www.aacr.org/
insertion_date 2018-01-17
journaleissn 1557-3265
journalissn 1078-0432
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The American Association for Cancer Research (AACR)
quelle Clinical Cancer Research
relation http://clincancerres.aacrjournals.org/cgi/content/short/24/2/334?rss=1
search_space articles
shingle_author_1 Arbour, K. C., Jordan, E., Kim, H. R., Dienstag, J., Yu, H. A., Sanchez-Vega, F., Lito, P., Berger, M., Solit, D. B., Hellmann, M., Kris, M. G., Rudin, C. M., Ni, A., Arcila, M., Ladanyi, M., Riely, G. J.
shingle_author_2 Arbour, K. C., Jordan, E., Kim, H. R., Dienstag, J., Yu, H. A., Sanchez-Vega, F., Lito, P., Berger, M., Solit, D. B., Hellmann, M., Kris, M. G., Rudin, C. M., Ni, A., Arcila, M., Ladanyi, M., Riely, G. J.
shingle_author_3 Arbour, K. C., Jordan, E., Kim, H. R., Dienstag, J., Yu, H. A., Sanchez-Vega, F., Lito, P., Berger, M., Solit, D. B., Hellmann, M., Kris, M. G., Rudin, C. M., Ni, A., Arcila, M., Ladanyi, M., Riely, G. J.
shingle_author_4 Arbour, K. C., Jordan, E., Kim, H. R., Dienstag, J., Yu, H. A., Sanchez-Vega, F., Lito, P., Berger, M., Solit, D. B., Hellmann, M., Kris, M. G., Rudin, C. M., Ni, A., Arcila, M., Ladanyi, M., Riely, G. J.
shingle_catch_all_1 Effects of Co-occurring Genomic Alterations on Outcomes in Patients with KRAS-Mutant Non-Small Cell Lung Cancer
Purpose: KRAS mutations occur in approximately 25% of patients with non–small cell lung cancer (NSCLC). Despite the uniform presence of KRAS mutations, patients with KRAS -mutant NSCLC can have a heterogeneous clinical course. As the pattern of co-occurring mutations may describe different biological subsets of patients with KRAS -mutant lung adenocarcinoma, we explored the effects of co-occurring mutations on patient outcomes and response to therapy. Experimental Design: We identified patients with advanced KRAS -mutant NSCLC and evaluated the most common co-occurring genomic alterations. Multivariate analyses were performed incorporating the most frequent co-mutations and clinical characteristics to evaluate association with overall survival as well as response to platinum–pemetrexed chemotherapy and immune checkpoint inhibitors. Results: Among 330 patients with advanced KRAS -mutant lung cancers, the most frequent co-mutations were found in TP53 (42%), STK11 (29%), and KEAP1 / NFE2L2 (27%). In a multivariate analysis, there was a significantly shorter survival in patients with co-mutations in KEAP1 / NFE2L2 [HR, 1.96; 95% confidence interval (CI), 1.33–2.92; P ≤ 0.001]. STK11 (HR, 1.3; P = 0.22) and TP53 (HR 1.11, P = 0.58) co-mutation statuses were not associated with survival. Co-mutation in KEAP1 / NFE2L2 was also associated with shorter duration of initial chemotherapy (HR, 1.64; 95% CI, 1.04–2.59; P = 0.03) and shorter overall survival from initiation of immune therapy (HR, 3.54; 95% CI, 1.55–8.11; P = 0.003). Conclusions: Among people with KRAS -mutant advanced NSCLC, TP53, STK11 , and KEAP1 / NFE2L2 are the most commonly co-occurring somatic genomic alterations. Co-mutation of KRAS and KEAP1 / NFE2L2 is an independent prognostic factor, predicting shorter survival, duration of response to initial platinum-based chemotherapy, and survival from the start of immune therapy. Clin Cancer Res; 24(2); 334–40. ©2017 AACR .
Arbour, K. C., Jordan, E., Kim, H. R., Dienstag, J., Yu, H. A., Sanchez-Vega, F., Lito, P., Berger, M., Solit, D. B., Hellmann, M., Kris, M. G., Rudin, C. M., Ni, A., Arcila, M., Ladanyi, M., Riely, G. J.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_2 Effects of Co-occurring Genomic Alterations on Outcomes in Patients with KRAS-Mutant Non-Small Cell Lung Cancer
Purpose: KRAS mutations occur in approximately 25% of patients with non–small cell lung cancer (NSCLC). Despite the uniform presence of KRAS mutations, patients with KRAS -mutant NSCLC can have a heterogeneous clinical course. As the pattern of co-occurring mutations may describe different biological subsets of patients with KRAS -mutant lung adenocarcinoma, we explored the effects of co-occurring mutations on patient outcomes and response to therapy. Experimental Design: We identified patients with advanced KRAS -mutant NSCLC and evaluated the most common co-occurring genomic alterations. Multivariate analyses were performed incorporating the most frequent co-mutations and clinical characteristics to evaluate association with overall survival as well as response to platinum–pemetrexed chemotherapy and immune checkpoint inhibitors. Results: Among 330 patients with advanced KRAS -mutant lung cancers, the most frequent co-mutations were found in TP53 (42%), STK11 (29%), and KEAP1 / NFE2L2 (27%). In a multivariate analysis, there was a significantly shorter survival in patients with co-mutations in KEAP1 / NFE2L2 [HR, 1.96; 95% confidence interval (CI), 1.33–2.92; P ≤ 0.001]. STK11 (HR, 1.3; P = 0.22) and TP53 (HR 1.11, P = 0.58) co-mutation statuses were not associated with survival. Co-mutation in KEAP1 / NFE2L2 was also associated with shorter duration of initial chemotherapy (HR, 1.64; 95% CI, 1.04–2.59; P = 0.03) and shorter overall survival from initiation of immune therapy (HR, 3.54; 95% CI, 1.55–8.11; P = 0.003). Conclusions: Among people with KRAS -mutant advanced NSCLC, TP53, STK11 , and KEAP1 / NFE2L2 are the most commonly co-occurring somatic genomic alterations. Co-mutation of KRAS and KEAP1 / NFE2L2 is an independent prognostic factor, predicting shorter survival, duration of response to initial platinum-based chemotherapy, and survival from the start of immune therapy. Clin Cancer Res; 24(2); 334–40. ©2017 AACR .
Arbour, K. C., Jordan, E., Kim, H. R., Dienstag, J., Yu, H. A., Sanchez-Vega, F., Lito, P., Berger, M., Solit, D. B., Hellmann, M., Kris, M. G., Rudin, C. M., Ni, A., Arcila, M., Ladanyi, M., Riely, G. J.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_3 Effects of Co-occurring Genomic Alterations on Outcomes in Patients with KRAS-Mutant Non-Small Cell Lung Cancer
Purpose: KRAS mutations occur in approximately 25% of patients with non–small cell lung cancer (NSCLC). Despite the uniform presence of KRAS mutations, patients with KRAS -mutant NSCLC can have a heterogeneous clinical course. As the pattern of co-occurring mutations may describe different biological subsets of patients with KRAS -mutant lung adenocarcinoma, we explored the effects of co-occurring mutations on patient outcomes and response to therapy. Experimental Design: We identified patients with advanced KRAS -mutant NSCLC and evaluated the most common co-occurring genomic alterations. Multivariate analyses were performed incorporating the most frequent co-mutations and clinical characteristics to evaluate association with overall survival as well as response to platinum–pemetrexed chemotherapy and immune checkpoint inhibitors. Results: Among 330 patients with advanced KRAS -mutant lung cancers, the most frequent co-mutations were found in TP53 (42%), STK11 (29%), and KEAP1 / NFE2L2 (27%). In a multivariate analysis, there was a significantly shorter survival in patients with co-mutations in KEAP1 / NFE2L2 [HR, 1.96; 95% confidence interval (CI), 1.33–2.92; P ≤ 0.001]. STK11 (HR, 1.3; P = 0.22) and TP53 (HR 1.11, P = 0.58) co-mutation statuses were not associated with survival. Co-mutation in KEAP1 / NFE2L2 was also associated with shorter duration of initial chemotherapy (HR, 1.64; 95% CI, 1.04–2.59; P = 0.03) and shorter overall survival from initiation of immune therapy (HR, 3.54; 95% CI, 1.55–8.11; P = 0.003). Conclusions: Among people with KRAS -mutant advanced NSCLC, TP53, STK11 , and KEAP1 / NFE2L2 are the most commonly co-occurring somatic genomic alterations. Co-mutation of KRAS and KEAP1 / NFE2L2 is an independent prognostic factor, predicting shorter survival, duration of response to initial platinum-based chemotherapy, and survival from the start of immune therapy. Clin Cancer Res; 24(2); 334–40. ©2017 AACR .
Arbour, K. C., Jordan, E., Kim, H. R., Dienstag, J., Yu, H. A., Sanchez-Vega, F., Lito, P., Berger, M., Solit, D. B., Hellmann, M., Kris, M. G., Rudin, C. M., Ni, A., Arcila, M., Ladanyi, M., Riely, G. J.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_4 Effects of Co-occurring Genomic Alterations on Outcomes in Patients with KRAS-Mutant Non-Small Cell Lung Cancer
Purpose: KRAS mutations occur in approximately 25% of patients with non–small cell lung cancer (NSCLC). Despite the uniform presence of KRAS mutations, patients with KRAS -mutant NSCLC can have a heterogeneous clinical course. As the pattern of co-occurring mutations may describe different biological subsets of patients with KRAS -mutant lung adenocarcinoma, we explored the effects of co-occurring mutations on patient outcomes and response to therapy. Experimental Design: We identified patients with advanced KRAS -mutant NSCLC and evaluated the most common co-occurring genomic alterations. Multivariate analyses were performed incorporating the most frequent co-mutations and clinical characteristics to evaluate association with overall survival as well as response to platinum–pemetrexed chemotherapy and immune checkpoint inhibitors. Results: Among 330 patients with advanced KRAS -mutant lung cancers, the most frequent co-mutations were found in TP53 (42%), STK11 (29%), and KEAP1 / NFE2L2 (27%). In a multivariate analysis, there was a significantly shorter survival in patients with co-mutations in KEAP1 / NFE2L2 [HR, 1.96; 95% confidence interval (CI), 1.33–2.92; P ≤ 0.001]. STK11 (HR, 1.3; P = 0.22) and TP53 (HR 1.11, P = 0.58) co-mutation statuses were not associated with survival. Co-mutation in KEAP1 / NFE2L2 was also associated with shorter duration of initial chemotherapy (HR, 1.64; 95% CI, 1.04–2.59; P = 0.03) and shorter overall survival from initiation of immune therapy (HR, 3.54; 95% CI, 1.55–8.11; P = 0.003). Conclusions: Among people with KRAS -mutant advanced NSCLC, TP53, STK11 , and KEAP1 / NFE2L2 are the most commonly co-occurring somatic genomic alterations. Co-mutation of KRAS and KEAP1 / NFE2L2 is an independent prognostic factor, predicting shorter survival, duration of response to initial platinum-based chemotherapy, and survival from the start of immune therapy. Clin Cancer Res; 24(2); 334–40. ©2017 AACR .
Arbour, K. C., Jordan, E., Kim, H. R., Dienstag, J., Yu, H. A., Sanchez-Vega, F., Lito, P., Berger, M., Solit, D. B., Hellmann, M., Kris, M. G., Rudin, C. M., Ni, A., Arcila, M., Ladanyi, M., Riely, G. J.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_title_1 Effects of Co-occurring Genomic Alterations on Outcomes in Patients with KRAS-Mutant Non-Small Cell Lung Cancer
shingle_title_2 Effects of Co-occurring Genomic Alterations on Outcomes in Patients with KRAS-Mutant Non-Small Cell Lung Cancer
shingle_title_3 Effects of Co-occurring Genomic Alterations on Outcomes in Patients with KRAS-Mutant Non-Small Cell Lung Cancer
shingle_title_4 Effects of Co-occurring Genomic Alterations on Outcomes in Patients with KRAS-Mutant Non-Small Cell Lung Cancer
timestamp 2025-06-30T23:32:04.178Z
titel Effects of Co-occurring Genomic Alterations on Outcomes in Patients with KRAS-Mutant Non-Small Cell Lung Cancer
titel_suche Effects of Co-occurring Genomic Alterations on Outcomes in Patients with KRAS-Mutant Non-Small Cell Lung Cancer
topic WW-YZ
uid ipn_articles_6139898