| General information |
| Database: | DB00827 |
| Objective: | EGFRmutant lung cancers responsive to reversible EGFR inhibitors (gefitinib/erlotinib) develop acquired resistance, mediated by secondsite EGFR T790M mutation in >50% of cases |
| Authors: | Janjigian YY, et al |
| Title: | Dual inhibition of EGFR with afatinib and cetuximab in kinase inhibitorresistant EGFRmutant lung cancer with and without T790M mutations. |
| Journal: | Cancer Discov. |
| Year: | 2014 |
| PMID: | 25074459 |
| Trial Design |
| Clinical Trial Id: | NCT01090011 |
| Agent: | afatinib and cetuximab
|
| Target: | NA
|
| Cancer Type: | lung cancer |
| Cancer Subtype: | kinase inhibitorresistant EGFRmutant lung cancer with and without T790M mutations |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | afatinib + cetuximab |
| Study Type: | a phase Ib, openlabel, uncontrolled, multicenter study |
| Key Patients Feature: | heavily pretreated patients with advanced EGFRmutant lung cancer and acquired resistance to erlotinib/gefitinib. |
| Biomarker: | Patients provided postacquiredresistance tumor samples for profiling EGFR mutations. |
| Biomark Analysis: | Afatinibcetuximab demonstrated robust clinical activity and a manageable safety profile in EGFRmutant lung cancers with acquired resistance to gefitinib or erlotinib, both with and without T790M mutations, warranting further investigation. |
| Control Group Info: | single arm |
| Treatment Info: | Afatinib was administered daily as oral medication, while cetuximab was administered intravenously. Initially, 10 patients were enrolled in the dosefindingphase: 4 patients received afatinib 40 mg daily plus cetuximab 250 mg/m2 every 2 weeks and 6 received the prespecified maximum dose of afatinib 40 mg daily plus cetuximab 500 mg/m2 every 2 weeks. The MTD was rapidly identified as afatinib 40 mg daily plus cetuximab 500 mg/m2 every 2 weeks |
| Primary End Point: | OR; PFS; duration of disease control; and duration of response, adverse events |
| Secondary End Point: | NA |
| Patients Number: | 126 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 0.29 |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 4.7 months (95% confidence interval, 4.36.4) |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | most common being rash (90%), diarrhea (71%), nail effects (57%), stomatitis (56%), fatigue (47%), and nausea (42%; |
| Conclusions: | This article reports the results of a trial combining afatinib and cetuximab in patients with acquired resistance and details the first clinical proofofconcept for the preclinical hypothesis that a significant proportion of tumors in patients with acquired resistance to gefitiniberlotinib remain dependent on EGFR signaling for survival. |