| General information |
| Database: | DB00146 |
| Objective: | a phase 2 study evaluated efficacy and safety of refametinib plus sorafenib in Asian patients with hepatocellular carcinoma |
| Authors: | Lim HY, et al |
| Title: | a phase II study of the efficacy and safety of the combination therapy of the MEK inhibitor refametinib (BAY 869766) plus sorafenib for Asian patients with unresectable hepatocellular carcinoma. |
| Journal: | Clin Cancer Res |
| Year: | 2014 |
| PMID: | 25294897 |
| Trial Design |
| Clinical Trial Id: | NCT01204177 |
| Agent: | BAY 869766
|
| Target: | Dual specificity mitogenactivated protein kinase kinase
|
| Cancer Type: | liver cancer |
| Cancer Subtype: | advanced hepatocellular carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | refametinib (BAY 869766)+sorafenib |
| Study Type: | a phase II study |
| Key Patients Feature: | All patients were aged 18 years or over and had a histologically or cytologically confirmed diagnosis of unresectable advanced or metastatic hepatocellular carcinoma from 14 centers in South Korea, Taiwan, Hong Kong, and Singapore |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Eligible patients received twicedaily refametinib 50 mg plus twicedaily sorafenib 200 mg (morning)/400 mg (evening), with dose escalation to sorafenib 400 mg twice daily from cycle 2 if no grade more than and equal to 2 handfoot skin reaction, fatigue, or gastrointestinal toxicity occurred. |
| Primary End Point: | DCR. |
| Secondary End Point: | OS, TTP, progression free survival, response rate, and duration of response. |
| Patients Number: | 95 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Best clinical responders had RAS mutations; majority of poor responders had wildtype RAS. |
| Disease Control Rate: | Disease control rate was 44.8% (primary efficacy analysis; n = 58). |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median time to progression was 122 days |
| Median OS A vs. C: | median overall survival was 290 days (n = 70). |
| Adverse Event(agent arm): | Most frequent drugrelated adverse events were diarrhea, rash, aspartate aminotransferase elevation, vomiting, and nausea. Dose modifications due to adverse events were necessary in almost all patients. |
| Conclusions: | Refametinib plus sorafenib showed antitumor activity in patients with hepatocellular carcinoma and was tolerated at reduced doses by most patients. Frequent dose modifications due to grade 3 adverse events may have contributed to limited treatment effect. Patients with RAS mutations appear to benefit from refametinibsorafenib combination. |