| General information |
| Database: | DB00805 |
| Objective: | Selumetinib (AZD6244, ARRY142886)+docetaxel increases median overall survival (OS) and significantly improves progression free survival (PFS) and objective response rate (ORR) compared with docetaxel alone in patients with KRAS mutant, stage IIIB/IV non small cell lung cancer (non small cell lung cancer; NCT00890825). |
| Authors: | J nne PA, et al |
| Title: | Impact of KRAS codon subtypes from a randomisedphase II trial of selumetinib plus docetaxel in KRAS mutant advanced non small cell lung cancer. |
| Journal: | Br J Cancer. |
| Year: | 2015 |
| PMID: | 26125448 |
| Trial Design |
| Clinical Trial Id: | NCT00890825 |
| Agent: | selumetinib
|
| Target: | Dual specificity mitogenactivated protein kinase kinase
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced non small cell lung cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | selumetinib + docetaxel |
| Study Type: | Retrospective analysis of a randomisedphase II trial |
| Key Patients Feature: | patients with histologically or cytologically confirmed, locally advanced or metastatic, KRAS mutant non small cell lung cancer (stage IIIB/IV), following failure of firstline chemotherapy. |
| Biomarker: | KRAS mutation status |
| Biomark Analysis: | In patients receiving selumetinib+docetaxel and harbouring KRAS G12C or G12V mutations there were trends towards greater improvement in OS, PFS and ORR compared with other KRAS mutations. |
| Control Group Info: | single arm |
| Treatment Info: | Treatment consisted of intravenous docetaxel 75 mg m 2 on day 1 of every 21day cycle in combination with either selumetinib hydrogen sulphate capsules 75 mg orally twice daily or matched placebo until disease progression or unacceptable toxic effects occurred. |
| Primary End Point: | Impact of KRAS codon subtypes |
| Secondary End Point: | NA |
| Patients Number: | 44 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | The ORR by KRAS mutation type in the selumetinib+docetaxel arm showed a numerically higher rate in MG1 compared with MG2 (46% and 26%, respectively; P=0.189) |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | for the selumetinib+docetaxel arm vs the placebo+docetaxel arm in MG1 and MG2 was 5.7 vs 1.4 months (HR 0.48, 80% CI: 0.31-0.74) and 4.9 vs 2.6 months (HR 0.72, 80% CI: 0.44-1.16), respectively |
| Median OS A vs. C: | for the selumetinib+docetaxel arm vs the placebo+docetaxel arm in MG1 and MG2 was 9.6 vs 4.4 months (HR 0.69, 80% CI: 0.44-1.09) and 8.6 vs 7.1 months (HR 0.96, 80% CI: 0.54-1.70), respectively |
| Adverse Event(agent arm): | NA |
| Conclusions: | Different KRAS mutations in non small cell lung cancer may influence selumetinibdocetaxel sensitivity. |