| General information |
| Database: | DB00073 |
| Objective: | No targeted therapies are available for KRASmutant non small cell lung cancer (non small cell lung cancer). Selumetinib is an inhibitor of MEK1/MEK2, downstream of KRAS, with preclinical evidence of synergistic activity with docetaxel in KRASmutant cancers. they did a prospective, randomised, phase 2 trial to assess selumetinib plus docetaxel in previously treated patients with advanced KRASmutant non small cell lung cancer. |
| Authors: | J nne PA, et al |
| Title: | Selumetinib plus docetaxel for KRASmutant advanced non small cell lung cancer: a randomised, multicentre, placebocontrolled, phase 2 study. |
| Journal: | Lancet Oncol. |
| Year: | 2013 |
| PMID: | 23200175 |
| Trial Design |
| Clinical Trial Id: | NCT00890825 |
| Agent: | selumetinib
|
| Target: | Dual specificity mitogenactivated protein kinase kinase
|
| 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: | a randomised, multicentre, placebocontrolled, phase II study |
| Key Patients Feature: | patients had histologically or cytologically confirmed stage IIIBIV KRASmutant non small cell lung cancer; had failed firstline therapy for advanced non small cell lung cancer |
| Biomarker: | KRASpositive |
| Biomark Analysis: | as in the conclusion |
| Control Group Info: | Aselumetinib group: selumetinib+docetaxel Cplacebo group: placebo+docetaxel |
| Treatment Info: | Patients were randomly assigned (in a 1:1 ratio) to either oral selumetinib (75 mg twice daily in a 21 day cycle) or placebo; all patients received intravenous docetaxel (75 mg/m(2) on day 1 of a 21 day cycle). |
| Primary End Point: | overall survival, analysed for all patients with confirmed KRAS mutations |
| Secondary End Point: | NA |
| Patients Number: | 83 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 37% vs none, p<0.0001 |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 5.3 vs 2.1, 0.58, 80% CI 0.420.79; onesided p=0.014 |
| Median OS A vs. C: | 9.4 vs 5.2, 0.80, 80% CI 0.561.14; onesided p=0.21 |
| Adverse Event(agent arm): | Adverse events of grade 3 or higher: 36 (82%)vs 28 (67%) grade 34 adverse events were neutropenia 67%;febrile neutropenia:18%, dyspnoea 2%;asthenia9% |
| Conclusions: | Selumetinib plus docetaxel has promising efficacy, albeit with a higher number of adverse events than with docetaxel alone, in previously treated advanced KRASmutant non small cell lung cancer. These findings warrant further clinical investigation of selumetinib plus docetaxel in KRASmutant non small cell lung cancer. |