Entry Detail
| General information | |
| Database: | DB00359 |
| Objective: | They aimed to assess the efficacy and safety of afatinib compared with methotrexate as secondline treatment in patients with recurrent or metastatic HNSCC progressing on or after platinumbased therapy. |
| Authors: | Machiels JP, et al |
| Title: | Afatinib versus methotrexate as secondline treatment in patients with recurrent or metastatic squamouscell carcinoma of the head and neck progressing on or after platinumbased therapy (LUXHead & Neck 1): an openlabel, randomisedphase 3 trial. |
| Journal: | Lancet Oncol. |
| Year: | 2015 |
| PMID: | 25892145 |
| Trial Design | |
| Clinical Trial Id: | NCT01345682 |
| Agent: | afatinib |
| Target: | Receptor proteintyrosine kinase erbB2 Epidermal growth factor receptor |
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced head and neck squamous cell carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | andomised, global, phase III, openlabel trial |
| Key Patients Feature: | Eligible patients were aged 18 years or older;had histologically or cytologically confirmed squamouscell carcinomas of the oral cavity, oropharynx, hypopharynx, or larynx that was recurrent, metastatic, or both and werenot amenable for salvage surgery or radiotherapy; had anEastern Cooperative Oncology Group (ECOG) performancestatus of 0 or 1; and had a life expectancy of at least3 months. Patients had documented evidence ofprogression on the basis of investigator assessment(measurable disease according to Response EvaluationCriteria in Solid Tumors [RECIST] version 1.1)17 after two ormore cycles of cisplatin (more than and equal to 60 mg/m2 per cycle or totalmore than and equal to 120 mg/m2 over 8 weeks) or carboplatin (area under theconcentrationtime curve more than and equal to 4 per cycle or total more than and equal to 8 over8 weeks) for recurrent or metastatic disease; |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | A:afatinib B:methotrexate |
| Treatment Info: | They randomly assigned eligible patients in a 2:1 ratio to receive oral afatinib (40 mg/day) or intravenous methotrexate (40 mg/m(2) per week), stratified by ECOG performance status and previous EGFRtargeted antibody therapy for recurrent or metastatic disease. Randomisation was done centrally with an interactive voice or theybbased response system. Clinicians and patients were not masked to treatment allocation; independent review of tumour response was done in a blinded manner. |
| Primary End Point: | progression free survival. |
| Secondary End Point: | Efficacy analyses and safety analyses |
| Patients Number: | 483 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | between Jan 10, 2012, and Dec 12, 2013, they enrolled 483 patients and randomly assigned 322 to afatinib and 161 to methotrexate. After a median followup of 6.7 months (IQR 3.19.0), progression free survival was longer in the afatinib group than in the methotrexate group (median 2.6 months [95% CI 2.02.7] for the afatinib group vs 1.7 months [1.52.4] for the methotrexate group; hazard ratio [HR] 0.80 [95% CI 0.650.98], p=0.030). The most frequent grade 3 or 4 drugrelated adverse events were rash or acne (31 [10%] of 320 patients in the afatinib group vs none of 160 patients in the methotrexate group), diarrhoea (30 [9%] vs three [2%]), stomatitis (20 [6%] vs 13 [8%]), fatigue (18 [6%] vs five [3%]), and neutropenia (1 [<1%] vs 11 [7%]); serious adverse events occurred in 44 (14%) of afatinibtreated patients and 18 (11%) of methotrexatetreated patients. |
| Disease Control Rate: | 49% patients given afatinib compared with 39% patients given methotrexate |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | median 2.6 months [95% CI 2.0-2.7] for the afatinib group vs 1.7 months [1.5-2.4] for the methotrexate group; hazard ratio [HR] 0.80 [95% CI 0.65-0.98], p=0.030). |
| Median OS A vs. C: | 6.8 months (95% CI 6.1-7.7) with afatinib and 6.0 months (5.2-7.8) with methotrexate (HR 0.96 [95% CI 0.77-1.19], p=0.70) |
| Adverse Event(agent arm): | The most frequent grade 3 or 4 drugrelated adverse events were rash or acne (31 [10%] of 320 patients in the afatinib group vs none of 160 patients in the methotrexate group), diarrhoea (30 [9%] vs three [2%]), stomatitis (20 [6%] vs 13 [8%]), fatigue (18 [6%] vs fi ve [3%]), and neutropenia (1 [<1%] vs 11 [7%]); serious adverse events occurred in 44 (14%) of afatinibtreated patients and 18 (11%) of methotrexatetreated patients. |
| Conclusions: | Afatinib was associated with significant improvements in progression free survival and had a manageable safety profile. These findings provide important new insights into the treatment of this patient population and support further investigations with irreversible ERBB family blockers in HNSCC. |