VEGF inhibitor fails to improve nonsquamous NSCLC overall survival

By Lynda Williams

Adding motesanib to carboplatin-paclitaxel does not boost overall survival (OS) in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC), including those with adenocarcinoma, say MONET1 investigators.

For patients with stage III/IV or recurrent NSCLC and no prior systemic treatment for advanced disease, median OS was a comparable 13.0 and 11.0 months in patients treated with motesanib 125 mg once daily (n=531) and placebo (n=541).

Nor did motesanib increase OS in a subset of patients with adenocarcinoma, at 13.5 versus 11.0 months, report Giorgio Scagliotti (University of Turin, Italy) and MONET1 (Motesanib NSCLC Efficacy and Tolerability) co-authors.

Treatment with the selective oral inhibitor of vascular endothelial growth factor (VEGF) 1, 2, and 3, platelet-derived growth factor receptor, and Kit did meet the secondary endpoints of significantly improved progression-free survival (median 5.6 vs 5.4 months) and objective response rate (40 vs 26%) compared with placebo.

However, motesanib was also associated with a significantly higher rate of grade 3 or greater adverse events than placebo (73 vs 59%), and grade 5 events (14 vs 9%), including nausea, vomiting, and gallbladder disorders. Indeed, motesanib-treated patients had a significantly higher rate of discontinuation due to adverse events than controls (31 vs 15%).

For the phase III trial, patients from Europe and the USA were randomly assigned to receive motesanib or placebo alongside 1:1 treatment with carboplatin to an area under the curve of 6 mg/mL per minute and paclitaxel 200 mg/m² for up to six 3-week cycles.

"The results from MONET1 add to the growing body of evidence that VEGF pathway inhibitors in combination with chemotherapy do not provide a significant clinical benefit to unselected patients with (nonsquamous) NSCLC," Scagliotti et al write.

"Additional studies do not seem to be warranted unless better patient selection using biomarkers, for example, can be achieved."

While such biomarkers "remain elusive," the researchers note that group analysis indicated that Asian patients, who made up a quarter of MONET1 participants, may have had a better response to motesanib than White patients. This suggests further research could be considered in this population, they say.

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