Addition of Motesanib to Paclitaxel/Carboplatin in East Asian Patients With Advanced NSCLC
The phase III MONET-A trial has shown that the addition of the multikinase/vascular endothelial growth factor receptor inhibitor motesanib to paclitaxel and carboplatin did not significantly improve progression-free survival in East Asian patients with stage IV/recurrent nonsquamous non–small cell lung cancer (NSCLC). These trial results were reported in the Journal of Clinical Oncology by Kubota et al. Findings of an earlier trial suggested a benefit with this approach in the subgroup of East Asian patients with advanced NSCLC.
Study Details
In the double-blind trial, 401 patients from 52 sites in Japan, Korea, Taiwan, and Hong Kong (71% enrolled in Japan) were randomized between July 2012 and March 2015 to receive motesanib plus paclitaxel/carboplatin (n = 197) or placebo plus paclitaxel/carboplatin (n = 204). Randomization was stratified by epidermal growth factor receptor (EGFR) status, region, and weight loss in the prior 6 months. Treatment consisted of oral motesanib at 125 mg or placebo once daily plus paclitaxel at 200 mg/m2 and carboplatin AUC = 6 mg/mL x min for up to six 3-week cycles. The primary endpoint was progression-free survival.
Progression-Free Survival
Median follow-up was 10.3 months in the motesanib group and 10.1 months in the placebo group. Median progression-free survival was 6.1 months in the motesanib group vs 5.6 months in the placebo group (stratified hazard ratio = 0.81, P = .0820). Median overall survival was not reached vs 21.6 months (P = .5514). Objective response rates were 60.1% vs 41.6% (P < .001), median time to response was 1.4 vs 1.6 months, and median duration of response was 5.3 vs 4.1 months. Subgroup analyses showed trends toward progression-free survival benefit with motesanib among subgroups with mutant EGFR, ≥ 5% prior weight loss, no prior adjuvant therapy, and prior radiation therapy.
Adverse Events
Grade 3 or 4 adverse events occurred in 86.7% vs 67.6% of patients, serious adverse events occurred in 48% vs 32.4%, and adverse events led to discontinuation of motesanib vs placebo in 32.7% vs 14.2% and to paclitaxel/carboplatin in 37.8% vs 25.5%. Adverse events that were more common in the motesanib group were gastrointestinal disorders, hypertension, and gallbladder-related disorders.
The investigators concluded: “Motesanib plus [paclitaxel/carboplatin] did not significantly improve [progression-free survival] versus placebo plus [paclitaxel/carboplatin] in East Asian patients with stage IV/recurrent nonsquamous non–small-cell lung cancer.”
Kaoru Kubota, MD, of the Nippon Medical School, Tokyo, is the corresponding author of the Journal of Clinical Oncology article.
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