Evaluation of the impact of tumor HPV status on outcome in patients with locally advanced unresectable head and neck squamous cell carcinoma (HNSCC) receiving cisplatin, 5-fluorouracil with or without docetaxel: a subset analysis of EORTC 24971 study.

Autor:	Psyrri A; Section of Medical Oncology, Second Department of Internal Medicine, School of Medicine, 'Attikon' University Hospital, National and Kapodistrian University of Athens, Athens, Greece., Fortpied C; EORTC Headquarters, Brussels, Belgium., Koutsodontis G; Section of Medical Oncology, Second Department of Internal Medicine, School of Medicine, 'Attikon' University Hospital, National and Kapodistrian University of Athens, Athens, Greece., Avgeris M; Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece., Kroupis C; Department of Clinical Biochemistry, School of Medicine, 'Attikon' University Hospital, National and Kapodistrian University of Athens, Athens, Greece., Goutas N; Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece., Menis J; EORTC Headquarters, Brussels, Belgium., Herman L; EORTC Headquarters, Brussels, Belgium., Giurgea L; EORTC Headquarters, Brussels, Belgium., Remenár É; Department of Head and Neck Surgery, National Institute of Oncology, Budapest, Hungary., Degardin M; Department of Oncology, Centre Oscar Lambret, Lille, France., Pateras IS; Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece., Langendijk JA; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., van Herpen CML; Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands., Awada A; Medical Oncology Clinic, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium., Germà-Lluch JR; Institut Català d'Oncologia, ICO L'Hospitalet, L'Hospitalet de Llobregat, Barcelona, Spain., Kienzer HR; 3rd Medical Department, Oncology and Hematology Center, Kaiser Franz Josef Spital/SMZ Sud, Vienna, Austria., Licitra L; Head and Neck Cancer Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, and University of Milan, Milan, Italy., Vermorken JB; Department of Medical Oncology, Antwerp University Hospital, Edegem, Belgium.
Jazyk:	angličtina
Zdroj:	Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2017 Sep 01; Vol. 28 (9), pp. 2213-2218.
DOI:	10.1093/annonc/mdx320
Abstrakt:	Background: EORTC 24971 was a phase III trial demonstrating superiority of induction regimen TPF (docetaxel, cisplatin, 5-fluorouracil) over PF (cisplatin/5-fluorouracil), in terms of progression-free (PFS) and overall survival (OS) in locoregionally advanced unresectable head and neck squamous cell carcinomas. We conducted a retrospective analysis of prospectively collected data aiming to evaluate whether only HPV(-) patients (pts) benefit from adding docetaxel to PF, in which case deintensifying induction treatment in HPV(+) pts could be considered. Patients and Methods: Pretherapy tumor biopsies (blocks or slides) were assessed for high-risk HPV by p16 immunohistochemistry, PCR and quantitative PCR. HPV-DNA+ and/or p16+ tumors were subjected to in situ hybridization (ISH) and HPV E6 oncogene expression qRT-PCR analysis. Primary and secondary objectives were to evaluate the value of HPV/p16 status as predictive factor of treatment benefit in terms of PFS and OS. The predictive effect was analyzed based on the model used in the primary analysis of the study with the addition of a treatment by marker interaction term and tested at two-sided 5% significance level. Results: Of 358, 119 pts had available tumor samples and 58 of them had oropharyngeal cancer. Median follow-up was 8.7 years. Sixteen of 119 (14%) evaluable samples were p16+ and 20 of 79 (25%) evaluable tumors were HPV-DNA+. 13 of 40 pts (33%) assessed with HPV-DNA ISH and 12 of 28 pts (43%) assessed for HPV E6 mRNA were positive. The preplanned analysis showed no statistical evidence of predictive value of HPV/p16 status for PFS (P = 0.287) or OS (P = 0.118). Conclusions: The incidence of HPV positivity was low in the subset of EORTC 24971 pts analyzed. In this analysis only powered to detect a large treatment by marker interaction, there was no statistical evidence that treatment effect found overall was different in magnitude in HPV(+) or HPV(-) pts. These results do not justify selection of TPF versus PF according to HPV status. (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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