Entry Detail
| General information | |
| Database: | DB00766 |
| Objective: | they aimed to assess the effect of afatinib on overall survival of patients with EGFR mutationpositive lung adenocarcinoma through an analysis of data from two openlabel, randomised, phase 3 trials. |
| Authors: | Yang JC, et al |
| Title: | Afatinib versus cisplatinbased chemotherapy for EGFR mutationpositive lung adenocarcinoma (LUXLung 3 and LUXLung 6): analysis of overall survival data from two randomised, phase 3 trials. |
| Journal: | Lancet Oncol. |
| Year: | 2015 |
| PMID: | 25589191 |
| Trial Design | |
| Clinical Trial Id: | NCT00949650 NCT01121393 |
| Agent: | afatinib |
| Target: | Receptor proteintyrosine kinase erbB2 Epidermal growth factor receptor |
| Cancer Type: | lung cancer |
| Cancer Subtype: | EGFR mutationpositive lung adenocarcinoma (LUXLung 3 and LUXLung 6 |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | analysis of overall survival data from two randomised, phase III trials. |
| Key Patients Feature: | Previously untreated patients with EGFR mutationpositive stage IIIB or IV lung adenocarcinoma were enrolled in LUXLung 3 (n=345) and LUXLung 6 (n=364). |
| Biomarker: | EGFR mutationpositive |
| Biomark Analysis: | The absence of an effect in patients with Leu858Arg EGFR mutations suggests that EGFR del19positive disease might be distinct from Leu858Argpositive disease and that these subgroups should be analysed separately in future trials. |
| Control Group Info: | Afatinib versus cisplatinbased chemotherapy |
| Treatment Info: | patients were randomly assigned in a 2:1 ratio to receive afatinib or chemotherapy (pemetrexedcisplatin [LUXLung 3] or gemcitabinecisplatin [LUXLung 6]), stratified by EGFR mutation (exon 19 deletion [del19], Leu858Arg, or other) and ethnic origin (LUXLung 3 only). they planned analyses of mature overall survival data in the intentiontotreat population after 209 (LUXLung 3) and 237 (LUXLung 6) deaths. |
| Primary End Point: | analysis of overall survival data |
| Secondary End Point: | NA |
| Patients Number: | 709 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | In LUXLung 3, median overall survival was 28.2 months (95% CI 24.633.6) in the afatinib group and 28.2 months (20.733.2) in the pemetrexedcisplatin group (HR 0.88, 95% CI 0.661.17, p=0.39). In LUXLung 6, median overall survival was 23.1 months (95% CI 20.427.3) in the afatinib group and 23.5 months (18.025.6) in the gemcitabinecisplatin group (HR 0.93, 95% CI 0.721.22, p=0.61). |
| Adverse Event(agent arm): | In both trials, the most common afatinibrelated grade 3-4 adverse events were rash or acne (37 [16%] of 229 patients in LUXLung 3 and 35 [15%] of 239 patients in LUXLung 6), diarrhoea (33 [14%] and 13 [5%]), paronychia (26 [11%] in LUXLung 3 only), and stomatitis or mucositis (13 [5%] in LUXLung 6 only). In LUXLung 3, neutropenia (20 [18%] of 111 patients), fatigue (14 [13%]) and leucopenia (nine [8%]) were the most common chemotherapyrelated grade 3-4 adverse events, while in LUXLung 6, the most common chemotherapyrelated grade 3-4 adverse events were neutropenia (30 [27%] of 113 patients), vomiting (22 [19%]), and leucopenia (17 [15%]). |
| Conclusions: | Although afatinib did not improve overall survival in the whole population of either trial, overall survival was improved with the drug for patients with del19 EGFR mutations. The absence of an effect in patients with Leu858Arg EGFR mutations suggests that EGFR del19positive disease might be distinct from Leu858Argpositive disease and that these subgroups should be analysed separately in future trials. |