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

• Published in: Journal of clinical oncology Vol. 30; no. 23; pp. 2829 - 2836
• Main Authors: Scagliotti, Giorgio V, Vynnychenko, Ihor, Park, Keunchil, Ichinose, Yukito, Kubota, Kaoru, Blackhall, Fiona, Pirker, Robert, Galiulin, Rinat, Ciuleanu, Tudor-Eliade, Sydorenko, Oleksandr, Dediu, Mircea, Papai-Szekely, Zsolt, Banaclocha, Natividad Martinez, McCoy, Sheryl, Yao, Bin, Hei, Yong-Jiang, Galimi, Francesco, Spigel, David R
• Format: Journal Article
• Language: English
• Published: United States American Society of Clinical Oncology 10.08.2012
• Subjects: Adenocarcinoma - drug therapy; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carboplatin - administration & dosage; Carcinoma, Non-Small-Cell Lung - drug therapy; Double-Blind Method; Female; Humans; Indoles - administration & dosage; Lung Neoplasms - drug therapy; Male; Middle Aged; Niacinamide - administration & dosage; Niacinamide - analogs & derivatives; Paclitaxel - administration & dosage; Receptors, Vascular Endothelial Growth Factor - antagonists & inhibitors; Young Adult
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2011.41.4987

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 with stage IIIB/IV or recurrent nonsquamous NSCLC (no prior systemic therapy for advanced disease) 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 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. 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. Motesanib plus carboplatin/paclitaxel did not significantly improve OS over carboplatin/paclitaxel alone in patients with advanced nonsquamous NSCLC or in the adenocarcinoma subset.