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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)985-991
Number of pages7
JournalAnnals of oncology : official journal of the European Society for Medical Oncology
Volume29
Issue number4
DOIs
Publication statusPublished - Apr 1 2018

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Safety
Positron-Emission Tomography
Magnetic Resonance Imaging
Glucose
Translational Medical Research
BIBW 2992
Carcinoma, squamous cell of head and neck
Diffusion Magnetic Resonance Imaging
Fluorine
Ambulatory Surgical Procedures
Renal Insufficiency
Comorbidity
Diarrhea
Neoplasms
Therapeutics
Biomarkers
Clinical Trials
Guidelines
Biopsy
Genes

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

In: Annals of oncology : official journal of the European Society for Medical Oncology, Vol. 29, No. 4, 01.04.2018, p. 985-991.

Research output: Contribution to journalArticle

Machiels, J-P, Bossi, P, Menis, J, Lia, M, Fortpied, C, Liu, Y, Lhommel, R, Lemort, M, Schmitz, S, Canevari, S, De Cecco, L, Guzzo, M, Bianchi, R, Quattrone, P, Crippa, F, Duprez, T, Lalami, Y, Quiriny, M, de Saint Aubain, N, Clement, PM, Coropciuc, R, Hauben, E & Licitra, LF 2018, 'Activity and safety of afatinib in a window preoperative EORTC study in patients with squamous cell carcinoma of the head and neck (SCCHN)', Annals of oncology : official journal of the European Society for Medical Oncology, vol. 29, no. 4, pp. 985-991. https://doi.org/10.1093/annonc/mdy013
Machiels, J-P ; Bossi, P ; Menis, J ; Lia, M ; Fortpied, C ; Liu, Y ; Lhommel, R ; Lemort, M ; Schmitz, S ; Canevari, S ; De Cecco, L ; Guzzo, M ; Bianchi, R ; Quattrone, P ; Crippa, F ; Duprez, T ; Lalami, Y ; Quiriny, M ; de Saint Aubain, N ; Clement, P M ; Coropciuc, R ; Hauben, E ; Licitra, L F. / Activity and safety of afatinib in a window preoperative EORTC study in patients with squamous cell carcinoma of the head and neck (SCCHN). In: Annals of oncology : official journal of the European Society for Medical Oncology. 2018 ; Vol. 29, No. 4. pp. 985-991.
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title = "Activity and safety of afatinib in a window preoperative EORTC study in patients with squamous cell carcinoma of the head and neck (SCCHN)",
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-na{\"i}ve 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.",
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T1 - Activity and safety of afatinib in a window preoperative EORTC study in patients with squamous cell carcinoma of the head and neck (SCCHN)

AU - Machiels, J-P

AU - Bossi, P

AU - Menis, J

AU - Lia, M

AU - Fortpied, C

AU - Liu, Y

AU - Lhommel, R

AU - Lemort, M

AU - Schmitz, S

AU - Canevari, S

AU - De Cecco, L

AU - Guzzo, M

AU - Bianchi, R

AU - Quattrone, P

AU - Crippa, F

AU - Duprez, T

AU - Lalami, Y

AU - Quiriny, M

AU - de Saint Aubain, N

AU - Clement, P M

AU - Coropciuc, R

AU - Hauben, E

AU - Licitra, L F

PY - 2018/4/1

Y1 - 2018/4/1

N2 - 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.

AB - 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.

U2 - 10.1093/annonc/mdy013

DO - 10.1093/annonc/mdy013

M3 - Article

C2 - 29346507

VL - 29

SP - 985

EP - 991

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 4

ER -