Motesanib Diphosphate in Progressive Differentiated Thyroid Cancer

Phase II Efficacy and Pharmacogenomic Study of Selumetinib (AZD6244; ARRY-142886) in Iodine-131 Refractory Papillary Thyroid Carcinoma with or without Follicular Elements

“…There were no complete responses reported in any of the studies. At the same time, using a modified definition of clinical benefit to standardize across studies (CB = CR + PR + SD) that has been previously suggested, selumetinib compares more favorably with other recent studies with CB of 57% versus published rates of 61% to 81% (27). Although IRPTC studies generally report SD outcomes, it is worth recalling that the natural history of the disease is frequently characterized by prolonged periods of slow progression.…”

“…Using prolonged SD measures as reported by other investigators, we observed 36% of patients with SD lasting over 24 weeks which compares favorably with the SD proportions with axitinib (38% over 16 weeks), sorafenib (53% from 14–89+ weeks), and motesanib (35% over 24 weeks; refs. 27–29). Similar to the case for response rates, patients treated with selumetinib showed PFS rates that were shorter than for the 3 comparator studies.…”

“…Only 16% of patients discontinued selumetinib therapy due to adverse events. Reported objective response rates have been greater in recent studies in advanced thyroid cancer of agents (axitinib, motesanib, sorafenib, and sunitinib) that target the vascular endothelial growth factor receptor (VEGFR) compared with agents such as selumetinib and gefitinib that do not target the VEGFR (27–29, 31, 32). This observation suggests that angiogenesis may be more important in progression of disease than signaling pathways known to be activated in the tumor such as RAS/RAF/MAPK activation.…”

An update on molecular biology of thyroid cancers

“…New smallmolecule protein-kinase inhibitors including axitinib [259], sorafenib [260,284,285], motesanib [262] and pazopanib [264] have shown promise in clinical trials on thyroid cancer. PLX4032 (also known as vemurafenib), a BRAF-V600E-specific inhibitor, has been recently approved by the FDA for the treatment of BRAFV600E-positive melanoma [286].…”

“…Both agents were determined to inhibit MAPK No study results posted yet [264] Motesanib Phase II completed Inhibits VEGF 14% [262] signaling and growth of human thyroid tumor cell lines and rat thyroid cells carrying the V600E BRAF and RET/PTC1 mutations. The growth of BRAF mutant tumor xenografts in nude mice was also shown to be suppressed [231].…”