Purpose: This phase II study investigated the efficacy and tolerability of motesanib, an investigational, highly selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit in advanced medullary thyroid cancer (MTC). Patients and Methods: Patients with locally advanced or metastatic, progressive or symptomatic MTC received motesanib 125 mg/d orally for up to 48 weeks or until unacceptable toxicity or disease progression. The primary end point was objective response by independent review. Other end points included duration of response, progression-free survival, safety, pharmacokinetics, and changes in tumor markers. Results: Of 91 enrolled patients who received motesanib, two (2%) achieved objective response (95% CI, 0.3% to 7.7%); their duration of response was 32 weeks (censored) and 21 weeks (disease progressed). Eighty-one percent of patients had stable disease (48% had durable stable disease ≥ 24 weeks), 8% had disease progression as best response, and 9% were not evaluated; 76% experienced a decrease from baseline in target lesion measurement. Median progression-free survival was 48 weeks (95% CI, 43 to 56 weeks). Among patients with tumor marker analysis, 69 (83%) of 83 and 63 (75%) of 84 had decreased serum calcitonin and carcinoembryonic antigen during treatment, respectively, compared with baseline. The most common treatment-related adverse events were diarrhea (41%), fatigue (41%), hypothyroidism (29%), hypertension (27%), and anorexia (27%). In pharmacokinetic analyses, motesanib trough concentrations were lower compared with differentiated thyroid cancer patients from the same study. Conclusion: Although the objective response rate was low, a significant proportion of MTC patients (81%) achieved stable disease while receiving motesanib.

Distant metastases are the main cause of death in patients with medullary thyroid cancer (MTC). These 21 recommendations focus on MTC patients with distant metastases and a detailed follow-up protocol of patients with biochemical or imaging evidence of disease, selection criteria for treatment, and treatment modalities, including local and systemic treatments based on the results of recent trials. Asymptomatic patients with low tumor burden and stable disease may benefit from local treatment modalities and can be followed up at regular intervals of time. Imaging is usually performed every 6–12 months, or at longer intervals of time depending on the doubling times of serum calcitonin and carcinoembryonic antigen levels. Patients with symptoms, large tumor burden and progression on imaging should receive systemic treatment. Indeed, major progress has recently been achieved with novel targeted therapies using kinase inhibitors directed against RET and VEGFR, but further research is needed to improve the outcome of these patients.

The incidence of thyroid cancer and the number of patients who die from this disease are increasing globally. Differentiated thyroid cancer (DTC) is the histologic subtype present in most patients and is primarily responsible for the increased overall incidence of thyroid cancer. Sorafenib is a multikinase inhibitor that targets several molecular signals believed to be involved in the pathogenesis of thyroid cancer, including those implicated in DTC. In phase II studies of patients with DTC, sorafenib treatment has yielded a median progression-free survival (PFS) of 58 to 84 weeks and disease control rates of 59% to 100%. The DECISION trial was designed to assess the ability of sorafenib to improve PFS in patients with locally advanced or metastatic, radioactive iodine (RAI)-refractory DTC.

Background: Anti-angiogenic Tyrosine Kinase Inhibitors (TKI) are the mainstay of advanced thyroid cancer (TC) treatment. Concern is rising about TKI-related toxicity. Objective: to determine the incidence and to investigate the risk factors of hemoptysis in TC patients during TKI treatment. Methods: We analyzed consecutive TC patients treated with TKI in our center between 2005 and 2013 and performed an independent review of CT-scan images for airway invasion assessment. Occurrence of grade 1–2 or grade 3–5 hemoptysis according to CTCAE version 4.03 and risk factors for hemoptysis were investigated. Results: 140 patients (89 males, median age: 52 years) with medullary (56%), differentiated (33%) and poorly differentiated TC (11%) were enrolled. Thyroidectomy±neck dissection was performed in 123 patients and neck/mediastinum external-beam radiotherapy (EBRT) in 41 (32% with therapeutic purpose and 68% with adjuvant purpose). Patients received from 1 to 4 lines of TKI (median 1). Median follow-up was 24 months. Airway invasion was found in 65 (46%) cases. Hemoptysis occurred in 9 patients: grade 1–2 in 7 cases (5%) and grade 3–5 in 2 (1.4%) cases (fatal in one). Hemoptysis was associated with presence of airway invasion [p= 0.04], poorly differentiated pathology [0.03], history of therapeutic EBRT [p= 0.003] and thyroidectomy without neck dissection [p= 0.02]. Conclusion: Airway invasion, poorly differentiated pathology, therapeutic EBRT and thyroidectomy without neck dissection are associated with and increased risk of hemoptysis in TC patients during anti-angiogenic TKI treatment. Further research is needed to confirm this data and to sort out interactions between these risk factors. A careful assessment of airway invasion is mandatory before TKI introduction.