An international, randomized, placebo-controlled, double-blind phase III study (MONET1) of motesanib plus carboplatin/paclitaxel (C/P) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC).

Abstract

LBA7512 Background: This study evaluated whether motesanib (a selective oral inhibitor of VEGFR 1, 2 and 3; PDGFR and Kit) plus C/P improved overall survival (OS) compared with placebo + C/P in patients (pts) with nonsquamous NSCLC and in a subset of pts with adenocarcinoma. Methods: Pts had stage IIIB/IV or recurrent nonsquamous NSCLC and no prior systemic therapy for advanced NSCLC. The study initially enrolled all histologies but was amended to exclude pts with squamous NSCLC owing to a high rate of hemoptysis. Pts were randomized 1:1 to receive up to six 3-wk cycles of C (AUC 6 mg/mL·min) and P (200 mg/m2) with either motesanib 125 mg QD (Arm A) or placebo QD (Arm B) orally continuously. The primary endpoint was OS; secondary endpoints included progression-free survival (PFS), adverse events (AEs), objective response rate (ORR) and association between placental growth factor (PLGF) change and OS. OS was evaluated using a stratified Cox model and 2-sided log-rank test (α=0.03 for nonsquamous pts and α=0.02 for adenocarcinoma pts). Results: 1090 pts with nonsquamous NSCLC were randomized (Arm A/B, n=541/549); 890 had adenocarcinoma (n=448/442). 61% were men; median age was 60 years (range 21–87); 83% had stage IV disease. At the time of analysis, 753 pts had died (608 pts with adenocarcinoma). Median follow-up was 10.6 mo. OS was not significantly improved in Arm A compared with Arm B (Table). In Arm A, PLGF analysis did not show an association with OS. The incidence of grade ≥3 AEs in Arms A/B was 73/59%. Grade ≥3 AEs occurring more frequently in Arm A than B included neutropenia (22/15%), diarrhea (9/1%), hypertension (7/1%) and cholecystitis (3/0%). The incidence of grade 5 AEs was 14/9% in Arms A/B. Conclusions: In pts with advanced nonsquamous NSCLC, treatment with motesanib + C/P did not significantly improve OS compared with C/P alone. [Table: see text]