Motesanib boosts carboplatin/paclitaxel efficacy in NSCLC

By Laura Cowen, medwireNews Reporter

Adding motesanib to carboplatin/paclitaxel significantly improves overall survival in Asian patients with nonsquamous non-small-cell lung cancer (NSCLC) compared with carboplatin/paclitaxel alone, researchers report.

Asian patients enrolled in the phase III MONET1 study who received carboplatin/paclitaxel plus motesanib (n=110) had a median overall survival (OS) of 20.9 months, compared with 14.5 months among those who received carboplatin/paclitaxel plus placebo (n=117).

Keunchil Park (Samsung Medical Center, Seoul, South Korea) and co-authors note that the results of this subset analysis of MONET1 data contrast with the main study findings, which showed no significant improvement in overall survival among patients who received motesanib versus those who did not.

“The reason for the differential effect of motesanib in the Asian subpopulation is unclear; however… There is evidence of epidemiologic, etiologic, and pharmacogenomic differences between Asian and Caucasian lung cancer patients, which may affect the impact of motesanib added to [carboplatin/paclitaxel],” they write in the Annals of Oncology.

Secondary study endpoints, including progression-free survival (PFS) and objective response rate (ORR) were also significantly greater in the patients who received carboplatin/paclitaxel plus motesanib compared with those who received carboplatin/paclitaxel plus placebo. Median PFS was 7.0 and 5.3 months, respectively and ORR (assessed by modified RECIST [Response Evaluation In Solid Tumours]) was 62% and 27%, respectively.

By contrast, no corresponding difference between treatment arms was observed in non-Asian patients (n=863) for OS (10.9 vs 10.7 months) or PFS (5.5 vs 5.4 months) and the difference in ORR was smaller (34 vs 25%).

A safety analysis showed that motesanib or placebo-related adverse events (AEs) were more common in Asian (n=222) than non-Asian (n=850) patients but fewer Asian patients discontinued motesanib treatment due to AEs than did non-Asian patients (26 vs 32%).

Among the Asian patients, grade 3 and above AEs were more common in the carboplatin/paclitaxel plus motesanib group compared with the carboplatin/paclitaxel plus placebo group (79 vs 61%), but the incidence of bleeding and thrombosis did not differ between the groups.

Park and team say that their findings are of “particular importance” because, based on market share, carboplatin/paclitaxel is the most commonly used first-line regimen for advanced NSCLC in Japan. In Korea, gemcitabine/cisplatin is more widely used than carboplatin/paclitaxel, they note.

A phase III study in Asian patients is ongoing to confirm these results.

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