50th Annual Meeting of the American Society of Clinical Oncology (ASCO):

Axitinib Active in Advanced Radioactive Iodine-Resistant Differentiated Thyroid Cancer and Refractory Medullary Thyroid Cancer

Axitinib appears to be active in patients with progressive advanced radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC) or unresectable medullary thyroid cancer (MTC), according to results of a retrospective analysis of a compassionate use program in Spain.

The findings were presented by Jaume Capdevila, MD, of the Vall d’Hebron University Hospital in Barcelona, Spain, and colleagues, on June 2, 2014, at the Annual Meeting of the American Society of Clinical Oncology in Chicago, Illinois.

Axitinib Response Rate
Axitinib, an oral inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, -2, and -3, is currently approved for the second-line treatment of patients with advanced renal cell carcinoma. In a phase 2 study of patients with advanced thyroid cancer of any histology, axitinib demonstrated an overall response rate of 30%.

Compassionate Use Outcomes
To further evaluate the efficacy and safety of axitinib in patients with advanced thyroid cancer, Dr. Capdevila and colleagues assessed outcomes with axitinib in a national compassionate use program in Spain.

The analysis included 41 patients with advanced RAI-refractory DTC (29 patients) or unresectable MTC (12 patients) with documented disease progression. The median age of enrolled patients was 62 years (range, 26-82 years); 51% of patients were male. The most common sites of metastasis were the lymph nodes (61%) and lung (56%). Ninety percent of patients had undergone prior surgery and 61% had received at least 1 prior multikinase inhibitor, including 24% who had received 2 or 3 prior multikinase inhibitors.

Patients received axitinib 5 mg twice daily until disease progression or intolerable adverse effects. The median duration of axitinib therapy was 6.2 months in patients with DTC and 4.9 months in patients with MTC. Dose reductions were required in 7 patients with DTC (26%) and in 4 patients with MTC (33%). There was a significant trend toward a shorter median treatment duration in more heavily pretreated patients (P < .05).

Axitinib was associated with an overall response rate of 41% in patients with DTC and 30% in patients with MTC. This difference was not statistically significant. Higher response rate was significantly associated with earlier line of treatment (P < .005), with axitinib showing the greatest activity as first-line therapy.  Response rates declined from 69.2% in the first-line setting (9 of 13 patients, including 1 complete response) to 20% in the second-line setting (2 of 10 patients), 0% in the third-line (0 of 8 patients), and 100% (1 of 1) in the fourth-line setting.

The median progression-free survival (PFS) was not significantly different in patients with DTC or MTC, at 6.5 months and 12.6 months, respectively. However, as was observed with response rate, median PFS declined with increasing lines of therapy. The median PFS observed with axitinib in the first-line, second-line, and third-line setting was 12.6 months, 8.6 months, and 3.9 months, respectively.

“To our knowledge,” the researchers noted, “this is the first time that resistance to sequential MKI [multikinase inhibitor] therapy in advanced thyroid cancer is suggested.”

Adverse Events
Axitinib was fairly well tolerated, with most adverse events grade 1-2 in severity and reflecting the safety profile observed in patients with metastatic renal cell carcinoma. The most common grade 3-4 adverse events included diarrhea, anorexia, and cardiac toxicity, each reported in 2 patients (5%). However, neither cardiac event was considered drug-related and both patients recovered.

The researchers concluded that prospective studies are warranted to further evaluate the role of axitinib in the treatment of patients with thyroid cancer.

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