Entry Detail
| General information | |
| Database: | DB00074 |
| Objective: | KRAS mutations are detected in 25% of non small cell lung cancer (non small cell lung cancer) and no targeted therapies are approved for this subset population. Trametinib, a selective allosteric inhibitor of MEK1/MEK2, demonstrated preclinical and clinical activity in KRASmutant non small cell lung cancer. they report a phase II trial comparing trametinib with docetaxel in patients with advanced KRASmutant non small cell lung cancer. |
| Authors: | Blumenschein GR Jr, et al. |
| Title: | A randomizedphase II study of the MEK1/MEK2 inhibitor trametinib (GSK1120212) compared with docetaxel in KRASmutant advanced non small cell lung cancer (non small cell lung cancer) |
| Journal: | Ann Oncol. |
| Year: | 2015 |
| PMID: | 25722381 |
| Trial Design | |
| Clinical Trial Id: | NCT01362296 |
| Agent: | trametinib |
| Target: | MEK2 Dual specificity mitogenactivated protein kinase kinase 1 |
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | KRASmutant non small cell lung cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase II |
| Key Patients Feature: | patients with histologically confirmed KRASmutant non small cell lung cancer previously treated with one prior platinumbased chemotherapy |
| Biomarker: | KRASmutant |
| Biomark Analysis: | as in the conclusion |
| Control Group Info: | docetaxel |
| Treatment Info: | pts were randomly assigned in a ratio of 2 : 1 to trametinib (2 mg orally once daily) or docetaxel (75 mg/m(2) i.v. every 3 weeks). Crossover to the other arm after disease progression was allowed |
| Primary End Point: | progression free survival (PFS). |
| Secondary End Point: | NA |
| Patients Number: | 129 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | PRs in the trametinib arm and 5 (12%) PRs in the docetaxel arm (P = 1.0000) |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 12weeks vs 11weeks, 1.14;0.751.75; P = 0.5197 |
| Median OS A vs. C: | 8(m) in the trametinib arm and was not reached in the docetaxel arm (0.97;0.521.83; P = 0.934). |
| Adverse Event(agent arm): | most common:rash, diarrhea, nausea, vomiting, and fatigue;most frequent grade 3 treatmentrelated Aes:hypertension, rash, diarrhea, and asthenia |
| Conclusions: | Trametinib showed similar(invalid) PFS and a response rate as docetaxel in patients with previously treated KRASmutantpositive non small cell lung cancer |