457 Background: Malignant pheochromocytoma/paraganglioma (P/PG) is a rare malignancy. Management of metastatic disease includes surgery, external radiation, 131I-MIBG and systemic chemotherapy. CVD (cyclophosphamide, vincristine and dacarbazine) is the only chemotherapy commonly used to treat metastatic disease. Putative anti-angiogenic agents such as the tyrosine kinase inhibitor (TKI) axitinib target a well-recognized pathway thought to be active in many tumors. Methods: Patients with histologically confirmed P/PG previously treated or naive to treatment received axitinib at initial dose of 5 mg BID. Primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival, response rate and safety. Results: Between January and September 2014 nine patients have been enrolled. The median age was 54.7 years, (range 42.5 – 70.5); median number of previous systemic treatments was one (range 0 – 3). Three of the nine patients achieved a partial response. An additional 5 patients have had tumor shrinkage insufficient to qualify as a partial response with only one patient response scored as progression. Tumor shrinkage has been observed in lymph node, soft tissue and lung metastases; and has been associated with reductions in circulating cathecholamines. Median time to progression has not been reached. A total of 50 cycles have been administered. Toxicity has led to a reduction of the dose of axitinib from a starting dose of 5 mg BID to 3 mg BID in six and 2 mg BID in two patients. The axitinib dose could be increased to 7 mg BID in only one patient Principal grade 3-4 toxicities included hypertension (6 patients), fatigue (4 patients), diarrhea (1 patient) and mucositis (1 patient). Conclusions: Preliminary data shows axitinib can result in tumor shrinkage in patients with a diagnosis of malignant P/PG. The high rate of dose reduction related to toxicity may reflect a different pharmacokinetic profile of the drug in these patients a possibility now under investigation. Clinical trial information: NCT01967576.

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