Nexavar sorafenib: Phase II data

Researchers from the M.D. Anderson Cancer Center reported data from the adaptive, open-label, U.S. Phase II BATTLE trial evaluating biomarker-integrated approaches of targeted therapy in 255 stage IV NSCLC patients receiving Tarceva erlotinib, Zactima vandetanib, Nexavar sorafenib or Tarceva plus Targretin bexarotene. Each treatment had the highest DCR at 8 weeks in certain biomarker subgroups. For example, Nexavar did the best against K-Ras mutations, Tarceva did the best against EGFR mutations (p=0.04), Zactima did the best against tumors with high VEGFR-2 expression (p=0.05), and Tarceva plus Targretin did the best against cyclin D1 ( CCND1; BCL1) expression (p=0.001) or EGFR amplifications (p=0.006). Patients with EGFR mutations or EGFR high polysomy did significantly worse on Nexavar (p=0.012 and p=0.048, respectively).

DCR at 8 weeks was 46% for all patients; 34% for Tarceva (n=58); 33% for Zactima (n=52); 58% for Nexavar (n=98); and 50% for Tarceva plus Targretin (n=36). The researchers also looked at the probability that a drug would yield >30% DCR for biomarkers subgroups. Nexavar had 100% probability of achieving >30% DCR in patients with K-Ras/ BRAF mutations (79% DCR); VEGF expression (64% DCR); and no biomarkers (61% DCR). Tarceva plus Targretin had 99% and 92% probabilities of achieving >30% DCR in patients with EGFR mutations, high polysomy, amplification or high gene copy number (55% DCR) and no biomarkers (56% DCR), respectively. Zactima had a 92% probability of achieving >30% DCR in the EGFR group (41% DCR). ...