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Biomarkers predict enhanced clinical outcomes with afatinib versus methotrexate in patients with second-line recurrent and/or metastatic head and neck cancer

BACKGROUND: In the phase III LUX-Head & Neck 1 (LUX-H&N1) trial, second-line afatinib significantly improved progression-free survival (PFS) versus methotrexate in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Here, we evaluated association of prespeci...

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Autores principales: Cohen, E. E. W., Licitra, L. F., Burtness, B., Fayette, J., Gauler, T., Clement, P. M., Grau, J. J., del Campo, J. M., Mailliez, A., Haddad, R. I., Vermorken, J. B., Tahara, M., Guigay, J., Geoffrois, L., Merlano, M. C., Dupuis, N., Krämer, N., Cong, X. J., Gibson, N., Solca, F., Ehrnrooth, E., Machiels, J.-P. H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834024/
https://www.ncbi.nlm.nih.gov/pubmed/28961833
http://dx.doi.org/10.1093/annonc/mdx344
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author Cohen, E. E. W.
Licitra, L. F.
Burtness, B.
Fayette, J.
Gauler, T.
Clement, P. M.
Grau, J. J.
del Campo, J. M.
Mailliez, A.
Haddad, R. I.
Vermorken, J. B.
Tahara, M.
Guigay, J.
Geoffrois, L.
Merlano, M. C.
Dupuis, N.
Krämer, N.
Cong, X. J.
Gibson, N.
Solca, F.
Ehrnrooth, E.
Machiels, J.-P. H.
author_facet Cohen, E. E. W.
Licitra, L. F.
Burtness, B.
Fayette, J.
Gauler, T.
Clement, P. M.
Grau, J. J.
del Campo, J. M.
Mailliez, A.
Haddad, R. I.
Vermorken, J. B.
Tahara, M.
Guigay, J.
Geoffrois, L.
Merlano, M. C.
Dupuis, N.
Krämer, N.
Cong, X. J.
Gibson, N.
Solca, F.
Ehrnrooth, E.
Machiels, J.-P. H.
author_sort Cohen, E. E. W.
collection PubMed
description BACKGROUND: In the phase III LUX-Head & Neck 1 (LUX-H&N1) trial, second-line afatinib significantly improved progression-free survival (PFS) versus methotrexate in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Here, we evaluated association of prespecified biomarkers with efficacy outcomes in LUX-H&N1. PATIENTS AND METHODS: Randomized patients with R/M HNSCC and progression following ≥2 cycles of platinum therapy received afatinib (40 mg/day) or methotrexate (40 mg/m(2)/week). Tumor/serum samples were collected at study entry for patients who volunteered for inclusion in biomarker analyses. Tumor biomarkers, including p16 (prespecified subgroup; all tumor subsites), EGFR, HER2, HER3, c-MET and PTEN, were assessed using tissue microarray cores and slides; serum protein was evaluated using the VeriStrat(®) test. Biomarkers were correlated with efficacy outcomes. RESULTS: Of 483 randomized patients, 326 (67%) were included in the biomarker analyses; baseline characteristics were consistent with the overall study population. Median PFS favored afatinib over methotrexate in patients with p16-negative [2.7 versus 1.6 months; HR 0.70 (95% CI 0.50–0.97)], EGFR-amplified [2.8 versus 1.5 months; HR 0.53 (0.33–0.85)], HER3-low [2.8 versus 1.8 months; HR 0.57 (0.37–0.88)], and PTEN-high [1.6 versus 1.4 months; HR 0.55 (0.29–1.05)] tumors. Afatinib also improved PFS in combined subsets of patients with p16-negative and EGFR-amplified tumors [2.7 versus 1.5 months; HR 0.47 (0.28–0.80)], and patients with p16-negative tumors who were EGFR therapy-naïve [4.0 versus 2.4 months; HR 0.55 (0.31–0.98)]. PFS was improved in afatinib-treated patients who were VeriStrat ‘Good’ versus ‘Poor’ [2.7 versus 1.5 months; HR 0.71 (0.49–0.94)], but no treatment interaction was observed. Afatinib improved tumor response versus methotrexate in all subsets analyzed except for those with p16-positive disease (n = 35). CONCLUSIONS: Subgroups of HNSCC patients who may achieve increased benefit from afatinib were identified based on prespecified tumor biomarkers (p16-negative, EGFR-amplified, HER3-low, PTEN-high). Future studies are warranted to validate these findings. CLINICAL TRIAL REGISTRATION: NCT01345682.
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spelling pubmed-58340242018-10-01 Biomarkers predict enhanced clinical outcomes with afatinib versus methotrexate in patients with second-line recurrent and/or metastatic head and neck cancer Cohen, E. E. W. Licitra, L. F. Burtness, B. Fayette, J. Gauler, T. Clement, P. M. Grau, J. J. del Campo, J. M. Mailliez, A. Haddad, R. I. Vermorken, J. B. Tahara, M. Guigay, J. Geoffrois, L. Merlano, M. C. Dupuis, N. Krämer, N. Cong, X. J. Gibson, N. Solca, F. Ehrnrooth, E. Machiels, J.-P. H. Ann Oncol Original Articles BACKGROUND: In the phase III LUX-Head & Neck 1 (LUX-H&N1) trial, second-line afatinib significantly improved progression-free survival (PFS) versus methotrexate in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Here, we evaluated association of prespecified biomarkers with efficacy outcomes in LUX-H&N1. PATIENTS AND METHODS: Randomized patients with R/M HNSCC and progression following ≥2 cycles of platinum therapy received afatinib (40 mg/day) or methotrexate (40 mg/m(2)/week). Tumor/serum samples were collected at study entry for patients who volunteered for inclusion in biomarker analyses. Tumor biomarkers, including p16 (prespecified subgroup; all tumor subsites), EGFR, HER2, HER3, c-MET and PTEN, were assessed using tissue microarray cores and slides; serum protein was evaluated using the VeriStrat(®) test. Biomarkers were correlated with efficacy outcomes. RESULTS: Of 483 randomized patients, 326 (67%) were included in the biomarker analyses; baseline characteristics were consistent with the overall study population. Median PFS favored afatinib over methotrexate in patients with p16-negative [2.7 versus 1.6 months; HR 0.70 (95% CI 0.50–0.97)], EGFR-amplified [2.8 versus 1.5 months; HR 0.53 (0.33–0.85)], HER3-low [2.8 versus 1.8 months; HR 0.57 (0.37–0.88)], and PTEN-high [1.6 versus 1.4 months; HR 0.55 (0.29–1.05)] tumors. Afatinib also improved PFS in combined subsets of patients with p16-negative and EGFR-amplified tumors [2.7 versus 1.5 months; HR 0.47 (0.28–0.80)], and patients with p16-negative tumors who were EGFR therapy-naïve [4.0 versus 2.4 months; HR 0.55 (0.31–0.98)]. PFS was improved in afatinib-treated patients who were VeriStrat ‘Good’ versus ‘Poor’ [2.7 versus 1.5 months; HR 0.71 (0.49–0.94)], but no treatment interaction was observed. Afatinib improved tumor response versus methotrexate in all subsets analyzed except for those with p16-positive disease (n = 35). CONCLUSIONS: Subgroups of HNSCC patients who may achieve increased benefit from afatinib were identified based on prespecified tumor biomarkers (p16-negative, EGFR-amplified, HER3-low, PTEN-high). Future studies are warranted to validate these findings. CLINICAL TRIAL REGISTRATION: NCT01345682. Oxford University Press 2017-10 2017-07-14 /pmc/articles/PMC5834024/ /pubmed/28961833 http://dx.doi.org/10.1093/annonc/mdx344 Text en © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Articles
Cohen, E. E. W.
Licitra, L. F.
Burtness, B.
Fayette, J.
Gauler, T.
Clement, P. M.
Grau, J. J.
del Campo, J. M.
Mailliez, A.
Haddad, R. I.
Vermorken, J. B.
Tahara, M.
Guigay, J.
Geoffrois, L.
Merlano, M. C.
Dupuis, N.
Krämer, N.
Cong, X. J.
Gibson, N.
Solca, F.
Ehrnrooth, E.
Machiels, J.-P. H.
Biomarkers predict enhanced clinical outcomes with afatinib versus methotrexate in patients with second-line recurrent and/or metastatic head and neck cancer
title Biomarkers predict enhanced clinical outcomes with afatinib versus methotrexate in patients with second-line recurrent and/or metastatic head and neck cancer
title_full Biomarkers predict enhanced clinical outcomes with afatinib versus methotrexate in patients with second-line recurrent and/or metastatic head and neck cancer
title_fullStr Biomarkers predict enhanced clinical outcomes with afatinib versus methotrexate in patients with second-line recurrent and/or metastatic head and neck cancer
title_full_unstemmed Biomarkers predict enhanced clinical outcomes with afatinib versus methotrexate in patients with second-line recurrent and/or metastatic head and neck cancer
title_short Biomarkers predict enhanced clinical outcomes with afatinib versus methotrexate in patients with second-line recurrent and/or metastatic head and neck cancer
title_sort biomarkers predict enhanced clinical outcomes with afatinib versus methotrexate in patients with second-line recurrent and/or metastatic head and neck cancer
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834024/
https://www.ncbi.nlm.nih.gov/pubmed/28961833
http://dx.doi.org/10.1093/annonc/mdx344
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