International, randomized, placebo-controlled, double-blind phase III study of motesanib plus carboplatin/paclitaxel in patients with advanced nonsquamous non-small-cell lung cancer: MONET1.
J Clin Oncol
; 30(23): 2829-36, 2012 Aug 10.
Article
in En
| MEDLINE
| ID: mdl-22753922
ABSTRACT
PURPOSE:
We evaluated whether motesanib (a selective oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3; platelet-derived 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 (NSCLC) and in the subset of patients with adenocarcinoma. PATIENTS ANDMETHODS:
Patients with stage IIIB/IV or recurrent nonsquamous NSCLC (no prior systemic therapy for advanced disease) were randomly assigned 11 to carboplatin (area under the curve, 6 mg/ml · min) and paclitaxel (200 mg/m(2)) intravenously for up to six 3-week cycles plus either motesanib 125 mg (arm A) or placebo (arm B) once daily orally. OS was the primary end point. Secondary end points included progression-free survival (PFS), objective response rate (ORR), adverse events (AEs), and association between placental growth factor (PLGF) change and OS.RESULTS:
A total of 1,090 patients with nonsquamous NSCLC were randomly assigned (arms A/B, n = 541 of 549); of those, 890 had adenocarcinoma (n = 448 of 442). Median OS 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). In descriptive analyses (arms A v B), median PFS was 5.6 months versus 5.4 months (P = < .001); ORR was 40% versus 26% (P < .001). There was no association between PLGF change and OS in arm A. The incidence of grade ≥ 3 AEs (arms A and B, 73% and 59%, respectively) and grade 5 AEs (14% and 9%, respectively) was higher with motesanib treatment.CONCLUSION:
Motesanib plus carboplatin/paclitaxel did not significantly improve OS over carboplatin/paclitaxel alone in patients with advanced nonsquamous NSCLC or in the adenocarcinoma subset.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Adenocarcinoma
/
Antineoplastic Combined Chemotherapy Protocols
/
Niacinamide
/
Carcinoma, Non-Small-Cell Lung
/
Receptors, Vascular Endothelial Growth Factor
/
Indoles
/
Lung Neoplasms
Type of study:
Clinical_trials
/
Prognostic_studies
Limits:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
J Clin Oncol
Year:
2012
Type:
Article
Affiliation country:
Italy