Phase 2 clinical trial of sunitinib as adjunctive treatment in patients with advanced differentiated thyroid cancer

Abstract

Objective: Our objective was to evaluate the efficacy and safety of sunitinib following at least one course of radioactive iodine treatment in patients with advanced differentiated thyroid cancer (DTC). The study endpoints included best response rate (including best objective response rate) and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, measurement of serum thyroglobulin (Tg), and toxicity evaluation. Design and methods: This was a single center, nonrandomized, open-label, phase 2 clinical trial. In total, 23 patients were enrolled and were treated with a starting daily, oral dose of 37.5 mg sunitinib. Patients were evaluated with imaging, laboratory tests, and physical examination periodically per protocol. Results: The mean best response was a decrease of 17.2% (S.D. 22.8) in tumor sum from baseline. Six (26%) patients achieved a partial response (PR), and 13 (57%) had stable disease (SD) for a clinical benefit rate (PRCSD) of 83%. The overall median PFS was 241 days (interquartile limits, 114-518). No statistically significant difference was observed between the medians of the baseline and post-treatment Tg values (PZ0.24). The most common adverse events included grades 1 and 2 decreases in blood cell counts (especially leukocytes), diarrhea, fatigue, hand-foot skin reaction, nausea, musculoskeletal pain, and hypertension.Conclusions: These data demonstrate that sunitinib exhibits significant anti-tumor activity in patients with advanced DTC. Since sunitinib was relatively well-tolerated, there is the potential for clinical benefit in these patients, and further investigation of this agent is warranted.

KinMap: a web-based tool for interactive navigation through human kinome data

“…Interestingly, a 2010 study of off-label use of both drugs demonstrated the efficacy in patients with widely metastatic, progressive differentiated thyroid cancer [23]. Subsequently, sorafenib was approved by the FDA for the treatment of metastatic differentiated thyroid cancer in 2013, while sunitinib is currently in phase 2 clinical trial as an adjunctive treatment for advanced differentiated thyroid cancer [24]. Moreover, off-label use of sorafenib showed positive results in personalized colon cancer therapy in a number of cases: e.g.…”

Novel targeted therapeutics for MEN2

“…Among the most advanced investigational compounds, sunitinib (Sutent, SU11248; Pfizer Ltd) has completed phase I and II trials in thyroid cancer (Dawson et al 2008, Carr et al 2010, Atallah et al 2016, Bikas et al 2016, Ravaud et al 2017 and is currently undergoing specific evaluation in RET fusion-positive tumors (NCT02450123). Sunitinib was part of a large indolinone compound collection at SUGEN Inc (later acquired by Pfizer), which was initially developed to block angiogenic kinases belonging to the split tyrosine kinase domain family (VEGFR, FGFR, PDGFR) (Sun et al 1998(Sun et al , 1999(Sun et al , 2000.…”

Immune responses in the thyroid cancer microenvironment: making immunotherapy a possible mission

“…sunitinib) and/or bisphosphonates, amongst others (Najjar & Finke 2013). Notably, sunitinib has recently demonstrated anti-tumor activity in advanced differentiated thyroid cancer (Bikas et al 2016). Although the benefit seen with sunitinib treatment has not been definitively attributed to MDSC depletion, it is known to augment MDSCs, which correlates with enhanced tumor-specific responses generated by cancer vaccines in preclinical models (Wesolowski et al 2013).…”