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Activity and safety of afatinib in a window preoperative EORTC study in patients with squamous cell carcinoma of the head and neck (SCCHN).

M Guzzo, L F Licitra, E Hauben, R Coropciuc, P M Clement, N de Saint Aubain, M Quiriny, Y Lalami, T Duprez, F Crippa, P Quattrone, R Bianchi, J-P Machiels, L De Cecco, S Canevari, S Schmitz, M Lemort, R Lhommel, Y Liu, C Fortpied, M Lia, J Menis, P Bossi

Journal: Annals of oncology : official journal of the European Society for Medical Oncology 2019;29(4):985-991

PMID: 29346507

Free Full Text on Elsevier Science View on PubMed

Abstract

BACKGROUND

To investigate the activity and safety of afatinib in the preoperative treatment of squamous cell carcinoma of the head and neck (SCCHN).

PATIENTS AND METHODS

This study was an open-label, randomized, multicenter, phase II window of opportunity trial. Treatment-naïve SCCHN patients selected for primary curative surgery were randomized (5 : 1 ratio) to receive afatinib during 14 days (day -15 until day -1) before surgery (day 0) or no treatment. Tumor biopsies, 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET), and magnetic resonance imaging (MRI) were carried out at diagnosis and just before surgery. The primary end point was metabolic FDG-PET response (according to EORTC guidelines). Other end points included response assessment based on the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, dynamic contrast-enhanced (DCE)-MRI, diffusion weighted (DW)-MRI, safety, and translational research (TR).

RESULTS

Thirty patients were randomized: 25 to afatinib and 5 to control arm. Of the 23 eligible patients randomized to afatinib, 16 (70%; 95% CI: 47% to 87%) patients had a partial metabolic FDG-PET response (PMR). Five patients (22%; 95% CI: 8% to 44%) showed a partial response by RECISTv1.1. Responses assessed via DCE-MRI and DWI-MRI did not show a strong association with PMR or RECIST. One patient discontinued afatinib after 11 days for grade 3 diarrhea with subsequent renal failure and 24 days delay in surgery. No grade 4 toxicities or surgical comorbidities related to afatinib were reported. TR results indicated that PMR was more frequent in the tumors with high Cluster3-hypoxia score expression and with TP53 wild type.

CONCLUSION

Afatinib given for 2 weeks to newly diagnosed SCCHN patients induces a high rate of FDG-PET partial metabolic response and partial response according to RECISTv1.1. Afatinib can be safely administered before surgery. Although exploratory, the hypoxic gene signature needs further investigations as a predictive biomarker of afatinib activity.

CLINICAL TRIAL REGISTRATION

ClinicalTrials.gov: NCT01538381.

Address: Department of Medical Oncolog, Institut Roi Albert II, Cliniques Universitaires Saint-Luc, Brussels, Italy; Department of Head and Neck Surger, Institut Roi Albert II, Cliniques Universitaires Saint-Luc, Brussels, Italy; Institut de Recherche Clinique et Expérimentale, Université Catholique de Louvain, Brussels, Belgium. Electronic address: [email protected].; Department of Head and Neck Medical Oncolog, Fondazione IRCCS Istituto Nazionale dei Tumori, University of Milan, Milan, Italy.; European Organization for Research and Treatment of Cancer (EORTC), Brussels, Italy.; Institut de Recherche Clinique et Expérimentale, Université Catholique de Louvain, Brussels, Belgium; Department of Nuclear Medicine, Cliniques Universitaires Saint-Luc, Brussels, Italy.; Department of Radiology, Institute Jules Bordet, Brussels, Belgium, Italy.; Department of Medical Oncolog, Institut Roi Albert II, Cliniques Universitaires Saint-Luc, Brussels, Italy; Department of Head and Neck Surger, Institut Roi Albert II, Cliniques Universitaires Saint-Luc, Brussels, Italy; Institut de Recherche Clinique et Expérimentale, Université Catholique de Louvain, Brussels, Belgium.; Functional Genomics and Bioinformatic, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; Department of Head and Neck Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; Nuclear Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; Department of Radiology, Cliniques Universitaires Saint-Luc, Brussels, Belgium, Belgium.; Department of Medical Oncology, Université Libre de Bruxelles, Brussels, Belgium.; Department of Head and Neck Surgery, Université Libre de Bruxelles, Brussels, Belgium.; Department of Patholog, Institute Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.; Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium.; Department of Oral and Maxillofacial Surgery, University Hospitals Leuven, Leuven, Belgium.; Department of Pathology, UZ Leuven, Leuven, Belgium.
DOI: 10.1093/annonc/mdy013

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MeSH Terms: Adult, Afatinib, Aged, Antineoplastic Agents, Biomarkers, Female, Fluorodeoxyglucose F18, Head and Neck Neoplasms, Humans, Male, Middle Aged, Positron-Emission Tomography, Preoperative Care, Squamous Cell Carcinoma of Head and Neck
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