(ChemotherapyAdvisor) – No significant improvement in overall survival (OS) was observed when patients with advanced nonsquamous non-small cell lung cancer (NSCLC) were treated with motesanib plus carboplatin/paclitaxel compared with carboplatin/paclitaxel alone, a randomized phase 3 study published in the Journal of Clinical Oncology online July 2 concluded.
The subset of patients with adenocarcinoma also did not benefit, noted Giorgio V. Scagliotti, MD, of the University of Turin, Torino, Italy, in reporting results of the MONET1 (Motesanib NSCLC Efficacy and Tolerability) trial on behalf of his colleagues.
Motesanib is a selective oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit. A total of 1,090 patients with stage IIIB/IV or recurrent nonsquamous NSCLC (890 with adenocarcinoma) who had received no prior systemic therapy for advanced disease were randomly assigned to carboplatin AUC6 and paclitaxel 200 mg/m2 IV for up to six 3-week cycles plus either oral motesanib 125mg/day or placebo.
Median OS in the motesanib arm was 13.0 months compared with 11.0 months in the placebo arm (HR 0.90 [95% CI, 0.78–1.04]; P=0.14); for those in the adenocarcinoma subset, median OS was 13.5 months and 11.0 months, respectively (HR 0.88 [95% CI, 0.75–1.03]; P=0.11). Median progression-free survival (PFS) was 5.6 months in the motesanib arm vs 5.4 months in the placebo arm (P<0.001) and objective response rate (ORR), 40% vs 26%, respectively (P<0.001).
No association between placental growth factor change and OS was observed in the motesanib arm. The incidence of grade 3 or higher adverse events (AEs) was 73% in the motesanib arm and 59% in the placebo arm; grade 5 AEs were higher with motesanib than with placebo (14% and 9%, respectively).
The authors noted that although the study did not meet its primary end point of OS, improvements in PFS and ORR in the motesanib arm “suggest some antitumor activity of the combination in this setting. However, the study also showed that motesanib treatment was associated with increased toxicity, which may have affected efficacy.”