Entry Detail
| General information | |
| Database: | DB01000 |
| Objective: | The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib are approved for firstline treatment of EGFR mutationpositive non small cell lung cancer (non small cell lung cancer). they aimed to compare the efficacy and safety of afatinib and gefitinib in this setting. |
| Authors: | Park K, et al |
| Title: | Afatinib versus gefitinib as firstline treatment of patients with EGFR mutationpositive non small cell lung cancer (LUXLung 7): a phase 2B, openlabel, randomised controlled trial. |
| Journal: | Lancet Oncol |
| Year: | 2016 |
| PMID: | 27083334 |
| Trial Design | |
| Clinical Trial Id: | NCT01466660 |
| Agent: | afatinib |
| Target: | Receptor proteintyrosine kinase erbB2 Epidermal growth factor receptor |
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced non small cell lung cancer harboring epidermal growth factor receptor mutations |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase IIB, openlabel, randomised controlled trial |
| Key Patients Feature: | Treatmentnaive patients with stage IIIB or IV non small cell lung cancer and a common EGFR mutation (exon 19 deletion or Leu858Arg) |
| Biomarker: | EGFR mutationpositive |
| Biomark Analysis: | Afatinib significantly improved outcomes in treatmentnaive patients with EGFRmutated non small cell lung cancer compared with gefitinib, with a manageable tolerability profile. |
| Control Group Info: | gefitinib |
| Treatment Info: | pts were randomly assigned (1:1) to receive afatinib (40 mg per day) or gefitinib (250 mg per day) until disease progression, or beyond if deemed beneficial by the investigator. Randomisation, stratified by EGFR mutation type and status of brain metastases, was done centrally using a validated number generating system implemented via an interactive voice or theybbased response system with a block size of four. |
| Primary End Point: | progression free survival by independent central review, timetotreatment failure, and overall survival. Efficacy analyses were done in the intentiontotreat population and safety analyses were done in patients who received at least one dose of study drug. |
| Secondary End Point: | NA |
| Patients Number: | 319 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | 70% in Afatinib arm and 56% in Gefitinib arm. |
| Disease Control Rate: | 91% in Afatinib arm and 87% in Gefitinib arm. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | median 11.0 months [95% CI 10.612.9] with afatinib vs 10.9 months [9.111.5] with gefitinib; hazard ratio [HR] 0.73 [95% CI 0.570.95], p=0.017 |
| Median OS A vs. C: | 27.9 months (95% CI 25.1-32.2) with afatinib versus 25.0 months (20.6-29.3) with gefitinib (HR 0.87 [95% CI 0.66-1.15]; p=0.33). |
| Adverse Event(agent arm): | The most common treatmentrelated grade 3 or 4 adverse events were diarrhoea (20 [13%] of 160 patients given afatinib vs two [1%] of 159 given gefitinib) and rash or acne (15 [9%] patients given afatinib vs five [3%] of those given gefitinib) and liver enzyme elevations (no patients given afatinib vs 14 [9%] of those given gefitinib). Serious treatmentrelated adverse events occurred in 17 (11%) patients in the afatinib group and seven (4%) in the gefitinib group. Ten (6%) patients in each group discontinued treatment due to drugrelated adverse events. 15 (9%) fatal adverse events occurred in the afatinib group and ten (6%) in the gefitinib group. All but one of these deaths were considered unrelated to treatment; one patient in the gefitinib group died from drugrelated hepatic and renal failure. |
| Conclusions: | Afatinib significantly improved outcomes in treatmentnaive patients with EGFRmutated non small cell lung cancer compared with gefitinib, with a manageable tolerability profile. These data are potentially important for clinical decision making in this patient population |