Single agent axitinib in the management of patients with progressive pheochromocytoma and paraganglioma.

person Antonio Tito Fojo Columbia University College of Physicians and Surgeons, James J. Peters VAMC, New York, Bronx, NY info_outline Antonio Tito Fojo, Andrea B Apolo, Maureen Edgerly, Karel Pacak, William Douglas Figg, Susan Elaine Bates, Jaydira Del Rivero

Authors person Antonio Tito Fojo Columbia University College of Physicians and Surgeons, James J. Peters VAMC, New York, Bronx, NY info_outline Antonio Tito Fojo, Andrea B Apolo, Maureen Edgerly, Karel Pacak, William Douglas Figg, Susan Elaine Bates, Jaydira Del Rivero Organizations Columbia University College of Physicians and Surgeons, James J. Peters VAMC, New York, Bronx, NY, Genitourinary Malignancies Branch, CCR, NCI, NIH, Bethesda, MD, National Institutes of Health, Bethesda, MD, National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, MD, Clinical Pharmacology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, Developmental Therapeutics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD Abstract Disclosures Research Funding No funding sources reported Background: Malignant pheochromocytomas and paragangliomas remain diseases that present those caring for patients with these diseases the dual challenges of hormonal excess and malignant behavior. Radiolabeled therapy with meta-iodobenzguanine (MIBG) and chemotherapy with a combination of cyclophosphamide, vincristine and dacarbazine can help in the management of patients whose disease has metastasized, but additional options are needed. The phase II FIRSTMAPPP study provided support for use of the tyrosine kinase inhibitor, sunitinib, in these malignancies with median PFS values of 8.9 vs. 3.6 months and ORRs of 31% vs. 8% for sunitinib vs placebo.Median duration of sunitinib therapy was 11 months. Concurrent with this study we launched a single arm trial to examine the activity of a similar TKI, axitinib. We report here the results of that study. Methods: Axitinib was self-administered at a dose of 5 mg every 12 hours continuously in a 28-day cycle. All patients were evaluated for dose adjustments to levels of 2, 3, 7, and 10 mg bid as options with intervals of at least 4 weeks between any dose escalations. Efficacy evaluations using conventional imaging were performed every 12 weeks. Documented evidence of disease progression was required prior to study entry. Results: Nineteen patients were enrolled; two did not receive treatment or less than one week of treatment. A partial response was achieved in 35.3% of patients, with a median reduction of tumor measurements of 34% and a median duration of response of 7.4 months. Median PFS was 7.9 months. Median duration of treatment was 9.5 months. Median OS was 29 months. Axitinib was well-tolerated with treatment-emergent adverse events with an attribution of possible, probable, and definite similar to those previously reported for the agent, including G1/2 fatigue, diarrhea, mucositis, and PPE in 42% to 63% and G1/2/3 hypertension in 79%, all managed with adjustments in antihypertensive medications No patient discontinued axitinib for an adverse event, nor had a prolonged suspension of treatment. Unfortunately, the study has been prematurely terminated by the sponsor. Conclusions: These results together with similar results reported recently with sunitinib provide strong evidence for the efficacy of sunitinib and axitinib, two VEGF tyrosine kinase inhibitors with similar characteristics, in the management of malignant pheochromocytoma and paragangliomas. Axitinib should be started at a dose of 5 mg bid and adjusted as tolerated. Despite its use in individuals with often difficult to treat hypertension, blood pressure management did not present a difficult challenge. Clinical trial information: NCT03839498.

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