Entry Detail
| General information | |
| Database: | DB00860 |
| Objective: | they evaluated whether motesanib (a selective oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3; plateletderived growth factor receptor; and Kit) combined with carboplatin/paclitaxel improved overall survival (OS) versus chemotherapy alone in patients with nonsquamous non small cell lung cancer (non small cell lung cancer) and in the subset of patients with adenocarcinoma. |
| Authors: | Scagliotti GV, et al |
| Title: | International, randomized, placebocontrolled, doubleblindphase III study of motesanib plus carboplatin/paclitaxel in patients with advanced nonsquamous non small cell lung cancer: MONET1. |
| Journal: | J Clin Oncol. |
| Year: | 2012 |
| PMID: | 22753922 |
| Trial Design | |
| Clinical Trial Id: | NCT00460317 |
| Agent: | motesanib |
| Target: | Mast/stem cell growth factor receptor Plateletderived growth factor receptor Vascular endothelial growth factor receptor 2 |
| 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: | Motesanib + carboplatin/paclitaxel |
| Study Type: | International, randomized, placebocontrolled, doubleblindphase III study |
| Key Patients Feature: | Patients with stage IIIB/IV or recurrent nonsquamous non small cell lung cancer (no prior systemic therapy for advanced disease) |
| Biomarker: | placental growth factor (PLGF) change |
| Biomark Analysis: | There was no association between PLGF change and OS in arm A. |
| Control Group Info: | motesanib plus carboplatin/paclitaxel versus placebo plus carboplatin/paclitaxel |
| Treatment Info: | patients were randomly assigned 1:1 to carboplatin (area under the curve, 6 mg/ml . min) and paclitaxel (200 mg/m(2)) intravenously for up to six 3week cycles plus either motesanib 125 mg (arm A) or placebo (arm B) once daily orally. |
| Primary End Point: | OS |
| Secondary End Point: | progression free survival (PFS), objective response rate (ORR), adverse events (AEs), and association between placental growth factor (PLGF) change and OS. |
| Patients Number: | 1090 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | ORR for all patients with nonsquamous histology (arm A, 40% v arm B, 26%) and for the adenocarcinoma subset (arm A, 39% v arm B, 25%) favored arm A. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 5.6 months versus 5.4 months (P = < .001); ORR was 40% versus 26% (P < .001). |
| Median OS A vs. C: | in arms A and B was 13.0 and 11.0 months, respectively (hazard ratio [HR], 0.90; 95% CI, 0.78 to 1.04; P = .14); median OS for the adenocarcinoma subset was 13.5 and 11.0 months, respectively (HR, 0.88; 95% CI, 0.75 to 1.03; P = .11). |
| Adverse Event(agent arm): | The incidence of AEs typically associated with VEGF pathway inhibitors was higher in arm A with respect to hypertension (Table 3) and grade more than and equal to 3 arterial thromboembolic (2% v < 1% in arm B) and hemorrhagic events (3% v 1%). Specific hemorrhagic events were gastrointestinal hemorrhage (n = 1 v n = 0), pulmonary hemorrhage (n = 2 v n = 1), and hemoptysis (n = 3 v n = 1). Grade more than and equal to 3 venous thromboembolic events occurred in 4% of patients in each treatment arm. |
| Conclusions: | Motesanib plus carboplatinpaclitaxel did not significantly improve OS over carboplatinpaclitaxel alone in patients with advanced nonsquamous non small cell lung cancer or in the adenocarcinoma subset. |