Entry Detail
| General information | |
| Database: | DB00060 |
| Objective: | Afatinib, an irreversible ErbBfamily blocker, has shown preclinical activity when tested in EGFR mutant models with mutations that confer resistance to EGFR tyrosinekinase inhibitors. they aimed to assess its efficacy in patients with advanced lung adenocarcinoma with previous treatment failure on EGFR tyrosinekinase inhibitors. |
| Authors: | Miller VA, et al |
| Title: | Afatinib versus placebo for patients with advanced, metastatic non small cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUXLung 1): a phase 2b/3 randomised trial. |
| Journal: | Lancet Oncol. |
| Year: | 2012 |
| PMID: | 22452896 |
| Trial Design | |
| Clinical Trial Id: | NCT00656136 |
| Agent: | afatinib |
| Target: | Receptor proteintyrosine kinase erbB2 Epidermal growth factor receptor |
| Cancer Type: | lung cancer |
| Cancer Subtype: | advanced lung adenocarcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase IIb/III |
| Key Patients Feature: | 86 centres in 15 countries (from three continents: Asia [China, Hong Kong, Korea, Singapore, Taiwan, Thailand], Europe [Belgium, Germany, France, Italy, The Netherlands, UK, Spain], and North America [Canada, USA]). |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | placebo |
| Treatment Info: | they used a computergenerated sequence to randomly allocate patients (2:1) to either afatinib (50 mg per day) or placebo; all patients received best supportive care. |
| Primary End Point: | overall survival (from date of randomisation to death), analysed on an intentiontotreat basis |
| Secondary End Point: | NA |
| Patients Number: | 585 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | No complete responses to treatmentwere noted; 29 (7%) patients had a partial response in the afatinib group, as did one patient in the placebo group.Confirmed objective responses were noted in 29 (7%)patients treated with afatinib by independent review andin 42 (11%) patients by investigator assessment |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 3.3 vs 1.1;0.38, 95% CI 0.310.48; p<0.0001 |
| Median OS A vs. C: | 10.8 vs 12.0;HR:1.08, 95% CI 0.861.35; p=0.74 |
| Adverse Event(agent arm): | diarrhoea (339 [87%] of 390 patients; 66 [17%] were grade 3) and rash or acne (305 [78%] patients; 56 [14%] were grade 3). (2 deaths) |
| Conclusions: | Although they recorded no benefit in terms of overall survival with afatinib (which might have been affected by cancer treatments given after progression in both groups), our findings for progression free survival and response to treatment suggest that afatinib could be of some benefit to patients with advanced lung adenocarcinoma who have failed at least 12 weeks of previous EGFR tyrosinekinase inhibitor treatment. |