| General information |
| Database: | DB00791 |
| Objective: | Linifanib, a potent, selective inhibitor of vascular endothelial growth factor (VEGF) and plateletderived growth factor (PDGF) receptors, has singleagent activity in non small cell lung cancer (non small cell lung cancer). they evaluated linifanib with carboplatin and paclitaxel as firstline therapy of advanced nonsquamous non small cell lung cancer. |
| Authors: | Ramalingam SS, et al |
| Title: | Randomizedphase II study of carboplatin and paclitaxel with either linifanib or placebo for advanced nonsquamous non small cell lung cancer. |
| Journal: | J Clin Oncol. |
| Year: | 2015 |
| PMID: | 25559798 |
| Trial Design |
| Clinical Trial Id: | NCT00716534 |
| Agent: | linifanib
|
| Target: | Macrophage colonystimulating factor 1
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced nonsquamous non small cell lung cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | carboplatin + paclitaxel with linifanib |
| Study Type: | Randomizedphase II study |
| Key Patients Feature: | Patients with stage IIIB/IV nonsquamous non small cell lung cancer |
| Biomarker: | Baseline plasma carcinoembryonic antigen/cytokeratin 19 fragments biomarker signature |
| Biomark Analysis: | Baseline plasma carcinoembryonic antigen/cytokeratin 19 fragments biomarker signature was associated with PFS improvement and a trend toward OS improvement with linifanib 12.5 mg. |
| Control Group Info: | carboplatin (area under the curve 6) and paclitaxel (200 mg/m(2)) with daily placebo (arm A), linifanib 7.5 mg (arm B), or linifanib 12.5 mg (arm C) |
| Treatment Info: | patients were randomly assigned to 3week cycles of carboplatin (area under the curve 6) and paclitaxel (200 mg/m(2)) with daily placebo (arm A), linifanib 7.5 mg (arm B), or linifanib 12.5 mg (arm C). |
| Primary End Point: | progression free survival (PFS); |
| Secondary End Point: | overall survival (OS) and objective response rate. |
| Patients Number: | 138 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 26% of patients receiving placebo, 43% receiving linifanib 7.5 mg, and 32% receiving linifanib 12.5 mg. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 5.4 months (95% CI, 4.2 to 5.7 months) in arm A (n = 47), 8.3 months (95% CI, 4.2 to 10.8 months) in arm B (n = 44), and 7.3 months (95% CI, 4.6 to 10.8 months) in arm C (n = 47). |
| Median OS A vs. C: | 11.3, 11.4, and 13.0 months in arms A, B, and C, respectively. |
| Adverse Event(agent arm): | NA |
| Conclusions: | Addition of linifanib to chemotherapy significantly improved PFS (arm B), with a modest trend for survival benefit (arm C) and increased toxicity reflective of known VEGFPDGF inhibitory effects. |