Entry Detail
| General information | |
| Database: | DB00064 |
| Objective: | Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have had a significant impact on non small cell lung cancer (non small cell lung cancer) outcomes, particularly for patients with EGFR mutations. Resistance emerges after 9 to 12 months, primarily mediated by the T790M resistance mutation. they studied neratinib, an irreversible panErbB TKI that may overcome T790M. |
| Authors: | Sequist LV, et al |
| Title: | Neratinib, an irreversible panErbB receptor tyrosine kinase inhibitor: results of a phase II trial in patients with advanced non small cell lung cancer. |
| Journal: | J Clin Oncol. |
| Year: | 2010 |
| PMID: | 20479403 |
| Trial Design | |
| Clinical Trial Id: | Clinical Trials repository link available onJCO.org. |
| Agent: | neratinib |
| Target: | mRNA of human epidermal growth factor receptor 2 Vascular endothelial growth factor receptor 2 Epidermal growth factor receptor |
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced non small cell lung cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase II:an openlabel, nonrandomized, threearm study |
| Key Patients Feature: | international, multicenter(non small cell lung cancer patients thought likely to benefit from an irreversible EGFR TKI: patients previously benefiting from firstgeneration TKI therapy who developed acquired resistance and TKIna ve patients with clinical characteristics of TKI response. ) |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Those with > or = 12 weeks of prior TKI therapy were placed in arm A if were EGFR mutation positive or arm B if were wildtype. Arm C included TKIna ve patients with adenocarcinoma and light smoking histories (< or = 20 packyears). All patients received daily oral neratinib, initially at 320 mg but subsequently reduced to 240 mg because of excessive diarrhea. |
| Primary End Point: | objective response rate (RR). |
| Secondary End Point: | NA |
| Patients Number: | 167 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | The RR was 3% in arm A and zero in arms B and C. No patients with known T790M responded. Notably, three of four patients with an exon 18 G719X EGFR mutation had a partial response and the fourth had stable disease lasting 40 weeks. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 3.7 (Severe diarrhoea) |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Diarrhea(50%ยกรบ25%) |
| Conclusions: | Neratinib had low activity in patients with prior benefit from TKIs and in TKI naive patients, potentially because of insufficient bioavailability from diarrhea imposed dose limitation. Responses were seen in patients with the rare G719X EGFR mutation, highlighting the importance of obtaining comprehensive genetic information on trials of targeted agents |