Addition of Motesanib to Paclitaxel/Carboplatin in East Asian Patients With Advanced NSCLC

Key Points

  • The addition of motesanib to paclitaxel and carboplatin did not significantly improve progression-free survival in East Asian patients with stage IV/recurrent nonsquamous NSCLC.
  • Severe adverse events were more common in the motesanib group.

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. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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