Entry Detail
| General information | |
| Database: | DB00919 |
| Objective: | Afatinib, an oral irreversible ErbB Family Blocker, has demonstrated efficacy and safety in epidermal growth factor receptor (EGFR) mutationpositive advanced lung adenocarcinoma. It is unknown whether such activity also occurs in patients with EGFR gene overexpression, regardless of mutation status. Thisphase II study investigated the activity and safety of afatinib in advanced non small cell lung cancer with increased EGFR gene copy number and/or gene amplification by fluorescence in situ hybridization (FISH), with or without EGFR mutation. |
| Authors: | Cappuzzo F, et al |
| Title: | Phase II study of afatinib, an irreversible ErbB family blocker, in EGFR FISHpositive non small cell lung cancer. |
| Journal: | J Thorac Oncol. |
| Year: | 2015 |
| PMID: | 25514804 |
| Trial Design | |
| Clinical Trial Id: | NCT00796549 |
| 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: | Phase II study |
| Key Patients Feature: | pts with advanced non small cell lung cancer with increased EGFR gene copy number and/or gene amplification by fluorescence in situ hybridization (FISH), with or without EGFR mutation. |
| Biomarker: | EGFR gene overexpression |
| Biomark Analysis: | The DCR was 50.7% overall (n = 35 of 69; median duration: 24.9 weeks) with higher DCRs observed in patients with gene amplification 64.0%; (n = 16 of 25), and in patients with EGFR mutationpositive tumors 66.7% (n = 8 of 12) |
| Control Group Info: | single arm |
| Treatment Info: | Patients received daily afatinib less than or equal to 50 mg (monotherapy). |
| Primary End Point: | objective response rate (ORR; primary), disease control rate (DCR), progression free survival (PFS), overall survival (OS), and safety |
| Secondary End Point: | NA |
| Patients Number: | 223 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | 13.00% |
| Disease Control Rate: | 50.70% |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 8.4 weeks (95% CI: 7.4-15.7) |
| Median OS A vs. C: | 50.4 weeks (95% CI: 33.4-64.0) |
| Adverse Event(agent arm): | Drugrelated AEs were reported in 64 out of 69 treated patients (92.8%), the most frequently occurring were rash/acne (82.6%), diarrhea (78.3%), and stomatitis (37.7%;).Treatment discontinuations due to AEs occurred in 24 patients (34.8%). The most common AEs leading to discontinuation were diarrhea (7.2%) and rash/acne (7.2%); in four patients (5.8%) the AEs were diseaserelated. Overall, 13 patients (18.8%) experienced AEs that led to the patient's death. None of the AEs leading to death were considered to be drugrelated. |
| Conclusions: | First or secondline afatinib demonstrated preliminary activity and manageable safety in EGFR FISHpositive patients with advanced non small cell lung cancer |