Entry Detail
| General information | |
| Database: | DB00712 |
| Objective: | This doubleblind, phase III study aimed to demonstrate that sunitinib plus FOLFIRI (fluorouracil, leucovorin, and irinotecan) was superior to placebo plus FOLFIRI in previously untreated metastatic colorectal cancer (mCRC). |
| Authors: | Carrato A, et al |
| Title: | Fluorouracil, leucovorin, and irinotecan plus either sunitinib or placebo in metastatic colorectal cancer: a randomized, phase III trial. |
| Journal: | J Clin Oncol. |
| Year: | 2013 |
| PMID: | 23358972 |
| Trial Design | |
| Clinical Trial Id: | NCT00457691 |
| Agent: | sunitinib |
| Target: | FL cytokine receptor Mast/stem cell growth factor receptor Vascular endothelial growth factor receptor 2 Plateletderived growth factor receptor |
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced colorectal cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Fluorouracil, leucovorin, and irinotecan plus sunitinib |
| Study Type: | randomized, doubleblind, placebocontrolledphase III study |
| Key Patients Feature: | patients were age 18 years, had Eastern Cooperative Oncology Groupperformance status (ECOG PS) of 0 or 1 and adequate organ function, and hadhistologically or cytologically confirmed colorectal adenocarcinoma with metastatic disease documented by diagnostic imaging. All patients had previouslyuntreated metastatic disease not amenable to surgery (although adjuvant therapy for primary CRC was permitted provided that 6 months had elapsedfrom the conclusion of adjuvant therapy to the documentation of recurrentdisease), were candidates for FOLFIRI therapy, and had one or more measurable lesions based on Response Evaluation Criteria in Solid Tumors, version1.0 (RECIST |
| Biomarker: | The correlation between genotype and clinical outcomes was also analyzed. |
| Biomark Analysis: | NA |
| Control Group Info: | sunitinib VS placebo |
| Treatment Info: | patients were randomly assigned to receive FOLFIRI and either sunitinib (37.5 mg per day) or placebo (4 weeks on treatment, followed by 2 weeks off [schedule 4/2]) until disease progression. |
| Primary End Point: | progression free survival (PFS) |
| Secondary End Point: | overall survival, safety, and patientreported outcomes |
| Patients Number: | 768 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median PFS for the sunitinib arm was 7.8 months (95% CI, 7.1 to 8.4 months) versus 8.4 months (95% CI, 7.6 to 9.2 months) for the placebo arm. |
| Median OS A vs. C: | 20.3 months (95% CI, 17.4 months to not reached [as a result of early study closure]) in the sunitinib plus FOLFIRI arm and 19.8 months (95% CI, 18.7 months to not reached) in the placebo plus FOLFIRI arm (HR, 1.171; 95% CI, 0.936 to 1.466; onesided stratified logrank P .916; Fig 2B). |
| Adverse Event(agent arm): | Sunitinib plus FOLFIRI was associated with more grade 3 adverse events and laboratory abnormalities than placebo (especially diarrhea, stomatitis/oral syndromes, fatigue, handfoot syndrome, neutropenia, thrombocytopenia, anemia, and febrile neutropenia). More deaths as a result of toxicity (12 v four) and significantly more dose delays, dose reductions, and treatment discontinuations occurred in the sunitinib arm. |
| Conclusions: | Sunitinib 37.5 mg per day (schedule 42) plus FOLFIRI is not superior to FOLFIRI alone and has a poorer safety profile. This combination regimen is not recommended for previously untreated mCRC. |