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-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.

• Authors: 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 Clement, R Coropciuc, E Hauben, L F Licitra
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 29 Issue 4 Pg. 985-991 (04 01 2018) ISSN: 1569-8041 [Electronic] England
• PMID: 29346507 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Biomarkers
• Fluorodeoxyglucose F18
• Afatinib

Topics

• Adult
• Afatinib (adverse effects, therapeutic use)
• Aged
• Antineoplastic Agents (adverse effects, therapeutic use)
• Biomarkers (metabolism)
• Female
• Fluorodeoxyglucose F18 (administration & dosage)
• Head and Neck Neoplasms (diagnostic imaging, drug therapy, metabolism, surgery)
• Humans
• Male
• Middle Aged
• Positron-Emission Tomography
• Preoperative Care
• Squamous Cell Carcinoma of Head and Neck (diagnostic imaging, drug therapy, metabolism, surgery)