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Single-arm, open label prospective trial to assess prediction of the role of ERCC1/XPF complex in the response of advanced NSCLC patients to platinum-based chemotherapy

BACKGROUND: Platinum-based therapy, combined or not with immune checkpoint inhibitors, represents a front-line choice for patients with non-small-cell lung cancer (NSCLC). Despite the improved outcomes in the last years for this malignancy, only a sub-group of patients have long-term benefit. Excisi...

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Autores principales: Ganzinelli, M., Linardou, H., Alvisi, M.F., Caiola, E., Lo Russo, G., Cecere, F.L., Bettini, A.C., Psyrri, A., Milella, M., Rulli, E., Fabbri, A., De Maglie, M., Romanelli, P., Murray, S., Broggini, M., Marabese, M., Garassino, M.C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809372/
https://www.ncbi.nlm.nih.gov/pubmed/33422766
http://dx.doi.org/10.1016/j.esmoop.2020.100034
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author Ganzinelli, M.
Linardou, H.
Alvisi, M.F.
Caiola, E.
Lo Russo, G.
Cecere, F.L.
Bettini, A.C.
Psyrri, A.
Milella, M.
Rulli, E.
Fabbri, A.
De Maglie, M.
Romanelli, P.
Murray, S.
Broggini, M.
Marabese, M.
Garassino, M.C.
author_facet Ganzinelli, M.
Linardou, H.
Alvisi, M.F.
Caiola, E.
Lo Russo, G.
Cecere, F.L.
Bettini, A.C.
Psyrri, A.
Milella, M.
Rulli, E.
Fabbri, A.
De Maglie, M.
Romanelli, P.
Murray, S.
Broggini, M.
Marabese, M.
Garassino, M.C.
author_sort Ganzinelli, M.
collection PubMed
description BACKGROUND: Platinum-based therapy, combined or not with immune checkpoint inhibitors, represents a front-line choice for patients with non-small-cell lung cancer (NSCLC). Despite the improved outcomes in the last years for this malignancy, only a sub-group of patients have long-term benefit. Excision repair cross-complementation group 1 (ERCC1) has been considered a potential biomarker to predict the outcome of platinum-based chemotherapy in NSCLC. However, the ERCC1 gene is transcribed in four splice variants where the isoform 202 was described as the only one active and able to complex Xeroderma pigmentosum group F-complementing protein (XPF). Here, we prospectively investigated if the active form of ERCC1, as assessed by the ERCC1/XPF complex (ERCC1/XPF), could predict the sensitivity to platinum compounds. PATIENTS AND METHODS: Prospectively enrolled, patients with advanced NSCLC treated with a first-line regimen containing platinum were centrally evaluated for ERCC1/XPF by a proximity ligation assay. Overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) were analyzed. RESULTS: The absence of the ERCC1/XPF in the tumor suggested a trend of worst outcomes in terms of both OS [hazard ratio (HR) 1.41, 95% confidence interval (CI) 0.67-2.94, P = 0.373] and PFS (HR 1.61, 95% CI 0.88-3.03, P = 0.123). ORR was marginally influenced in ERCC1/XPF-negative and -positive groups [odds ratio (stable disease + progressive disease versus complete response + partial response) 0.87, 95% CI 0.25-3.07, P = 0.832]. CONCLUSION: The lack of ERCC1/XPF complex in NSCLC tumor cells might delineate a group of patients with poor outcomes when treated with platinum compounds. ERCC1/XPF absence might well identify patients for whom a different therapeutic approach could be necessary.
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spelling pubmed-78093722021-01-22 Single-arm, open label prospective trial to assess prediction of the role of ERCC1/XPF complex in the response of advanced NSCLC patients to platinum-based chemotherapy Ganzinelli, M. Linardou, H. Alvisi, M.F. Caiola, E. Lo Russo, G. Cecere, F.L. Bettini, A.C. Psyrri, A. Milella, M. Rulli, E. Fabbri, A. De Maglie, M. Romanelli, P. Murray, S. Broggini, M. Marabese, M. Garassino, M.C. ESMO Open Original Research BACKGROUND: Platinum-based therapy, combined or not with immune checkpoint inhibitors, represents a front-line choice for patients with non-small-cell lung cancer (NSCLC). Despite the improved outcomes in the last years for this malignancy, only a sub-group of patients have long-term benefit. Excision repair cross-complementation group 1 (ERCC1) has been considered a potential biomarker to predict the outcome of platinum-based chemotherapy in NSCLC. However, the ERCC1 gene is transcribed in four splice variants where the isoform 202 was described as the only one active and able to complex Xeroderma pigmentosum group F-complementing protein (XPF). Here, we prospectively investigated if the active form of ERCC1, as assessed by the ERCC1/XPF complex (ERCC1/XPF), could predict the sensitivity to platinum compounds. PATIENTS AND METHODS: Prospectively enrolled, patients with advanced NSCLC treated with a first-line regimen containing platinum were centrally evaluated for ERCC1/XPF by a proximity ligation assay. Overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) were analyzed. RESULTS: The absence of the ERCC1/XPF in the tumor suggested a trend of worst outcomes in terms of both OS [hazard ratio (HR) 1.41, 95% confidence interval (CI) 0.67-2.94, P = 0.373] and PFS (HR 1.61, 95% CI 0.88-3.03, P = 0.123). ORR was marginally influenced in ERCC1/XPF-negative and -positive groups [odds ratio (stable disease + progressive disease versus complete response + partial response) 0.87, 95% CI 0.25-3.07, P = 0.832]. CONCLUSION: The lack of ERCC1/XPF complex in NSCLC tumor cells might delineate a group of patients with poor outcomes when treated with platinum compounds. ERCC1/XPF absence might well identify patients for whom a different therapeutic approach could be necessary. Elsevier 2021-01-07 /pmc/articles/PMC7809372/ /pubmed/33422766 http://dx.doi.org/10.1016/j.esmoop.2020.100034 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research
Ganzinelli, M.
Linardou, H.
Alvisi, M.F.
Caiola, E.
Lo Russo, G.
Cecere, F.L.
Bettini, A.C.
Psyrri, A.
Milella, M.
Rulli, E.
Fabbri, A.
De Maglie, M.
Romanelli, P.
Murray, S.
Broggini, M.
Marabese, M.
Garassino, M.C.
Single-arm, open label prospective trial to assess prediction of the role of ERCC1/XPF complex in the response of advanced NSCLC patients to platinum-based chemotherapy
title Single-arm, open label prospective trial to assess prediction of the role of ERCC1/XPF complex in the response of advanced NSCLC patients to platinum-based chemotherapy
title_full Single-arm, open label prospective trial to assess prediction of the role of ERCC1/XPF complex in the response of advanced NSCLC patients to platinum-based chemotherapy
title_fullStr Single-arm, open label prospective trial to assess prediction of the role of ERCC1/XPF complex in the response of advanced NSCLC patients to platinum-based chemotherapy
title_full_unstemmed Single-arm, open label prospective trial to assess prediction of the role of ERCC1/XPF complex in the response of advanced NSCLC patients to platinum-based chemotherapy
title_short Single-arm, open label prospective trial to assess prediction of the role of ERCC1/XPF complex in the response of advanced NSCLC patients to platinum-based chemotherapy
title_sort single-arm, open label prospective trial to assess prediction of the role of ercc1/xpf complex in the response of advanced nsclc patients to platinum-based chemotherapy
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809372/
https://www.ncbi.nlm.nih.gov/pubmed/33422766
http://dx.doi.org/10.1016/j.esmoop.2020.100034
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