Tailored Therapies for Advanced Thyroid Cancers Move a Step Closer

research highlights cancer Tailored therapies for advanced thyroid cancers move a step closer

he findings of several recently year was 66%. a strong correlation was published phase ii trials suggest observed between individual response and tthat personalized treatment might the plasma concentration of pazopanib soon become a reality for patients with during the first treatment cycle. advanced thyroid cancers. in a second trial, Huan Ha et al. Few options are currently available to enrolled 11 patients with PDGFr-positive, treat advanced thyroid cancers, which advanced anaplastic thyroid cancer. tend to respond poorly to conventional the investigators aimed to evaluate the chemotherapy. as a consequence, response of these tumors to imatinib, an novel therapeutic strategies that exploit inhibitor of PDGFr, Kit and BCr–aBl. biological pathways involved in thyroid Participants received 400 mg imatinib cancer are now being explored. twice daily; the dosage was lowered to Formation of a de novo blood supply 300 mg if adverse events occurred. tumor is required to sustain tumor growth. responses were assessed every 8 weeks.

the process of angiogenesis occurs via response rate was evaluable in eight © Dreamstime activation of receptor tyrosine kinases, patients: two achieved a partial response including vascular endothelial growth and four exhibited stable disease. no significantly from baseline after 1 week factor receptor (veGFr) and platelet- patients achieved a complete response of treatment and correlated with tumor derived growth factor receptor (PDGFr), to imatinib. the 6-month, progression- response. a marked separation of patients proteins that are constitutively active in free survival rate was 27%, with an who achieved a partial response versus some thyroid tumors. Blocking the activity overall survival rate of 46%. three of the those who did not was observed at a of these kinases with multitarget drugs, participants required dose reductions after 4.7-fold increase in PlGF concentration. such as sorafenib, has already shown some experiencing adverse events. a serum PlGF level above this cut-off promise in the treatment of patients with the studies of Bible et al. and Ha et al. value was associated with a 30% response advanced thyroid cancers. provide proof of principle that targeting rate, compared with just a 3% response rate Keith Bible and colleagues investigated angiogenesis could be beneficial for below this level. the efficacy of pazopanib (an inhibitor of patients with advanced thyroid cancers. the next step will be to evaluate the veGFr, PDGFr and Kit) in 37 patients However, in order to truly tailor therapy, efficacy of these angiogenesis inhibitors with progressive, metastatic thyroid clinicians need to know who is most in phase iii clinical trials. the costs and cancers that were refractory to treatment likely to respond to these novel drugs. risks involved must also be assessed. with radioactive iodine. Participants this issue was addressed by michael Bass However, as Bass points out, “the ability received 800 mg pazopanib daily, and colleagues. these researchers had to quickly identify responders would administered continuously in 4-week previously shown that the concentration of allow exclusion of nonresponders, thereby cycles, until drug intolerance and/or placenta growth factor (PlGF; a member sparing them from potential side effects disease progression occurred. the primary of the veGF family) is elevated after and allowing them to more quickly end point was the tumor response rate. administration of motesanib—an inhibitor explore alternative therapies.” the study group included patients of veGFr, PDGFr and Kit—in a Vicky Heath with follicular, Hürthle cell and dose-dependent fashion. Furthermore, papillary thyroid cancers. treatment the increase in PlGF correlated with was discontinued in 22 patients owing a reduction in tumor size. the team, Original articles Bible, K. C. et al. Efficacy of pazopanib to disease progression; 16 patients therefore, decided to evaluate PlGF as in progressive, radioiodine-refractory, metastatic required dose reductions and two patients a potential biomarker of response to differentiated thyroid cancers: results of a phase 2 consortium study. Lancet Oncol. 11, 962–972 (2010) | withdrew from the study as the result of motesanib therapy. Ha, H. T. et al. A phase II study of imatinib in patients with adverse events. no patients had a complete Bass et al. measured circulating levels advanced anaplastic thyroid cancer. Thyroid 20, 975–980 response to pazopanib; however, 18 of PlGF in 184 patients who received (2010) | Bass, M. B. et al. Biomarkers as predictors of patients experienced a partial effect 125 mg motesanib daily to treat advanced response to treatment with motesanib in patients with (48% response rate). the probability differentiated or medullary thyroid progressive advanced thyroid cancer. J. Clin. Endocrinol. Metab. doi:10.1210/jc.2010-0947 of this response lasting for more than 1 cancers. mean serum PlGF levels increased