Rationale and design of LUX-Head & Neck 1: a randomised, Phase III trial of afatinib versus methotrexate in patients with recurrent and/or metastatic head and neck squamous cell carcinoma who progressed after platinum-based therapy
| العنوان: | Rationale and design of LUX-Head & Neck 1: a randomised, Phase III trial of afatinib versus methotrexate in patients with recurrent and/or metastatic head and neck squamous cell carcinoma who progressed after platinum-based therapy |
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| المؤلفون: | Lisa Licitra, Robert I. Haddad, Ezra E.W. Cohen, Makoto Tahara, Jean-Pascal Machiels |
| المساهمون: | UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Unité d'oncologie médicale, UCL - (SLuc) Centre du cancer |
| المصدر: | BMC Cancer, Vol. 14, no.1, p. 473 (2014) BMC Cancer BMC cancer, vol 14, iss 1 |
| بيانات النشر: | BioMed Central Ltd., 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Oncology, Cancer Research, Afatinib, medicine.medical_treatment, law.invention, Study Protocol, Randomized controlled trial, Clinical Protocols, law, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, Neoplasm Metastasis, 6.2 Cellular and gene therapies, Cancer, Cetuximab, Local, Head and Neck Neoplasms, 6.1 Pharmaceuticals, Retreatment, Public Health and Health Services, Carcinoma, Squamous Cell, Disease Progression, Metastatic, Recurrent, medicine.drug, medicine.medical_specialty, Clinical Trials and Supportive Activities, Oncology and Carcinogenesis, Head and neck, Rare Diseases, Phase III, Clinical Research, Internal medicine, medicine, Genetics, Humans, Oncology & Carcinogenesis, Dental/Oral and Craniofacial Disease, Platinum, Chemotherapy, business.industry, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Evaluation of treatments and therapeutic interventions, medicine.disease, Head and neck squamous-cell carcinoma, Clinical trial, Orphan Drug, Neoplasm Recurrence, Methotrexate, Squamous Cell, Quinazolines, Neoplasm Recurrence, Local, business, Progressive disease |
| الوصف: | BackgroundPatients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) receiving platinum-based chemotherapy as their first-line treatment have a dismal prognosis, with a median overall survival (OS) of ~7 months. Methotrexate is sometimes used following platinum failure or in patients not fit enough for platinum therapy, but this agent has not demonstrated any OS improvement. Targeted therapies are a novel approach, with the EGFR-targeting monoclonal antibody cetuximab (plus platinum-based chemotherapy) approved in the US and Europe in the first-line R/M setting, and as monotherapy following platinum failure in the US. However, there is still a high unmet medical need for new treatments that improve outcomes in the second-line R/M setting following failure on first-line platinum-containing regimens. Afatinib, an irreversible ErbB family blocker, was recently approved for the first-line treatment of EGFR mutation-positive metastatic non-small cell lung cancer. Afatinib has also shown clinical activity similar to cetuximab in a Phase II proof-of-concept HNSCC trial. Based on these observations, the Phase III, LUX-Head & Neck 1 study is evaluating afatinib versus methotrexate in R/M HNSCC patients following progression on platinum-based chemotherapy in the R/M setting.Methods/designPatients with progressive disease after one first-line platinum-based chemotherapy are randomised 2:1 to oral afatinib (starting dose 40 mg once daily) or IV methotrexate (starting dose 40 mg/m(2) once weekly) administered as monotherapy with best supportive care until progression or intolerable adverse events. Efficacy of afatinib versus methotrexate will be assessed in terms of progression-free survival (primary endpoint). Disease progression will be evaluated according to RECIST v1.1 by investigator and independent central review. Secondary endpoints include OS, tumour response and safety. Health-related quality of life and biomarker assessments will also be performed.DiscussionIf the LUX-Head & Neck 1 trial meets its primary endpoint, it will demonstrate the ability of afatinib to elicit an improved treatment benefit versus a commonly used chemotherapy agent in the second-line treatment of R/M HNSCC patients who have failed on first-line platinum-based therapy, confirm the clinical efficacy of afatinib observed in the Phase II proof-of-concept study, and establish a new standard of care for this patient population. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bd91181fc94fa7c2e6f6074db671bc75Test https://hdl.handle.net/2078.1/147206Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....bd91181fc94fa7c2e6f6074db671bc75 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |