Afatinib versus placebo as adjuvant therapy after chemoradiation in a double-blind, phase III study (LUX-Head & Neck 2) in patients with primary unresected, clinically intermediate-to-high-risk head and neck cancer: study protocol for a randomized contro

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• 作者：Barbara Burtness (74)
  Jean P Bourhis (75)
  Jan B Vermorken (76)
  Kevin J Harrington (77) (78)
  Ezra EW Cohen (79)
  
  74. Yale University School of Medicine ; 333 Cedar Street ; New Haven ; CT ; 06520 ; USA
  75. Centre Hospitalier Universitaire Vaudois ; Lausanne ; Switzerland
  76. Antwerp University Hospital ; Edegem ; Belgium
  77. Head and Neck Unit ; The Royal Marsden Hospital ; London ; UK
  78. Division of Radiotherapy and Imaging ; Institute of Cancer Research ; London ; UK
  79. University of California San Diego Moores Cancer Center ; La Jolla ; CA ; USA
  
• 关键词：Adjuvant ; Afatinib ; Head and neck ; Local advanced ; Phase III ; Unfavourable risk
• 刊名：Trials
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：15
• 期：1
• 全文大小：716 KB
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• 刊物主题：Medicine/Public Health, general; Biomedicine general; Statistics for Life Sciences, Medicine, Health Sciences;
• 出版者：BioMed Central
• ISSN：1745-6215

文摘

Background Over 50% of patients with head and neck squamous cell carcinoma (HNSCC) present with locoregionally advanced disease. Those at intermediate-to-high risk of recurrence after definitive therapy exhibit advanced disease based on tumour size or lymph node involvement, non-oropharynx primary sites, human papillomavirus (HPV)-negative oropharyngeal cancer, or HPV-positive oropharynx cancer with smoking history (>10-pack-years). Non-surgical approaches include concurrent chemoradiotherapy, induction chemotherapy followed by definitive radiotherapy or chemoradiotherapy, or radiotherapy alone. Following locoregional therapies (including surgical salvage of residual cervical nodes), no standard intervention exists. Overexpression of epidermal growth factor receptor (EGFR), an ErbB family member, is associated with poor prognosis in HNSCC. EGFR-targeted cetuximab is the only targeted therapy that impacts overall survival and is approved for HNSCC in the USA or Europe. However, resistance often occurs, and new approaches, such as targeting multiple ErbB family members, may be required. Afatinib, an irreversible ErbB family blocker, demonstrated antiproliferative activity in preclinical models and comparable clinical efficacy with cetuximab in a randomized phase II trial in recurrent or metastatic HNSCC. LUX-Head & Neck 2, a phase III study, will assess adjuvant afatinib versus placebo following chemoradiotherapy in primary unresected locoregionally advanced intermediate-to-high-risk HNSCC. Methods/design Patients with primary unresected locoregionally advanced HNSCC, in good clinical condition with unfavourable risk of recurrence, and no evidence of disease after chemoradiotherapy will be randomized 2:1 to oral once-daily afatinib (40 mg starting dose) or placebo. As HPV status will not be determined for eligibility, unfavourable risk is defined as non-oropharynx primary site or oropharynx cancer in patients with a smoking history (>10 pack-years). Treatment will continue for 18 months or until recurrence or unacceptable adverse events occur. The primary endpoint measure is duration of disease-free survival; secondary endpoint measures are disease-free survival rate at 2 years, overall survival, health-related quality of life and safety. Discussion Given the unmet need in the adjuvant treatment of intermediate-to-high-risk HNSCC patients, it is expected that LUX-Head & Neck 2 will provide new insights into treatment in this setting and might demonstrate the ability of afatinib to significantly improve disease-free survival, compared with placebo. Trial registration ClinicalTrials.gov NCT01345669.