Phase III Study of Motesanib Plus Carboplatin/Paclitaxel in Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer: MONET1

J Clin Oncol. 2012 Jul 2. [Epub ahead of print]

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.

Scagliotti GV, Vynnychenko I, Park K, Ichinose Y, Kubota K, Blackhall F, Pirker R, Galiulin R, Ciuleanu TE, Sydorenko O, Dediu M, Papai-Szekely Z, Banaclocha NM, McCoy S, Yao B, Hei YJ, Galimi F, Spigel DR.

Source

Giorgio V. Scagliotti, University of Turin, S. Luigi Hospital, Turin, Italy; Ihor Vynnychenko, Sumy State University, Sumy; Oleksandr Sydorenko, Zaporizhzhya State Medical University, Zaporizhzhya, Ukraine; Keunchil Park, Sungkyunkwan University School of Medicine, Seoul, Korea; Yukito Ichinose, National Kyushu Cancer Center, Fukuoka; Kaoru Kubota, Nippon Medical School, Tokyo, Japan; Fiona Blackhall, The Christie National Health Services Foundation Trust, Manchester, United Kingdom; Robert Pirker, Medical University Vienna, Vienna, Austria; Rinat Galiulin, Omsk Regional Oncology Center, Omsk, Russia; Tudor-Eliade Ciuleanu, Oncology Institute Ion Chiricuta, Cluj-Napoca; Mircea Dediu, Institute of Oncology, Bucharest, Romania; Zsolt Papai-Szekely, St George Hospital, Szekesfehervar, Hungary; Natividad Martinez Banaclocha, Hospital General Universitario, Elche, Spain; Sheryl McCoy, Bin Yao, Yong-jiang Hei, Francesco Galimi, Amgen, Thousand Oaks, CA; and David R. Spigel, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN.

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 AND METHODS

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.

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.