Entry Detail
| General information | |
| Database: | DB00711 |
| Objective: | This randomized, doubleblind, placebocontrolled, phase IIb study evaluated adding sorafenib to firstline modified FOLFOX6 (mFOLFOX6) for metastatic colorectal cancer (mCRC). |
| Authors: | Tabernero J, et al |
| Title: | Sorafenib in combination with oxaliplatin, leucovorin, and fluorouracil (modified FOLFOX6) as firstline treatment of metastatic colorectal cancer: the RESPECT trial. |
| Journal: | Clin Cancer Res. |
| Year: | 2013 |
| PMID: | 23532888 |
| Trial Design | |
| Clinical Trial Id: | NCT00865709 |
| Agent: | sorafenib |
| Target: | Vascular endothelial growth factor receptor 1 BRaf protooncogene serine/threonineprotein kinase Protooncogene tyrosineprotein kinase receptor ret |
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced colorectal cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Sorafenib + oxaliplatin, leucovorin, and fluorouracil (modified FOLFOX6) |
| Study Type: | a phase IIb, randomized, doubleblind trial |
| Key Patients Feature: | Eligible patients were 18 years old, with histologicallyconfirmed, measurable metastatic adenocarcinoma of thecolon or rectum (stage IV; ref. 25), and an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.Prior radiotherapy was allowed, but at least 1 measurable, nonirradiated, metastatic lesion was required, as was atumor tissue sample for analysis of KRAS and BRAF mutations. Patients who had received prior chemotherapy formetastatic disease were not eligible, nor were patients withbrain metastases, active cardiac disease, or serious bonemarrow, liver, or renal dysfunction. Patients who hadreceived adjuvant treatment for CRC, including a FOLFOXregimen, were eligible provided that they had completedtreatment at least 12 months before randomization. |
| Biomarker: | KRAS and BRAF status |
| Biomark Analysis: | KRAS and BRAF status did not seem to impact treatment outcomes but the subgroups were small. |
| Control Group Info: | sorafenib (400 mg b.i.d.) VS placebo |
| Treatment Info: | patients were randomized to sorafenib (400 mg b.i.d.) or placebo, combined with mFOLFOX6 (oxaliplatin 85 mg/m(2); levoleucovorin 200 mg/m(2); fluorouracil 400 mg/m(2) bolus and 2400 mg/m(2) continuous infusion) every 14 days. |
| Primary End Point: | progression free survival (PFS). |
| Secondary End Point: | NA |
| Patients Number: | 198 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | 84.5% in sorafenib arm; 90.1 in placebo arm. |
| Median Time to Progression: | 9.2 months in the sorafenib arm and 9.0 months in the placebo arm (HR 0.83; 95% CI, 0.59- 1.17) |
| Median PFS A vs. C: | median PFS for sorafenib plus mFOLFOX6 was 9.1 months versus 8.7 months for placebo plus mFOLFOX6 (HR 0.88; 95% CI, 0.64-1.23; P 0.46). |
| Median OS A vs. C: | 17.6 months in the sorafenib arm and 18.1 months in the placebo arm (HR 1.13; 95% CI, 0.79-1.61; P 0.51). |
| Adverse Event(agent arm): | The most common grade 3/4 adverse events in the sorafenib and placebo arms were neutropenia (48% vs. 22%), peripheral neuropathy (16% vs. 21%), and grade 3 hand-foot skin reaction (20% vs. 0%). Treatment discontinuation because of adverse events was 9% and 6%, respectively. |
| Conclusions: | This study did not detect a PFS benefit with the addition of sorafenib to firstline mFOLFOX6 for mCRC. KRAS and BRAF status did not seem to impact treatment outcomes but the subgroups they were small. These results do not support further development of sorafenib in combination with mFOLFOX6 in molecularly unselected patients with mCRC. |