Axitinib in Progressive Metastatic Pheochromocytoma and Paraganglioma: Results of a Phase II Study
- 1Department of Surgery, Columbia University, New York, NY, Department of Medicine, Columbia University, New York, NY
Abstract
PurposeMetastatic pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine malignancies with limited systemic treatment options. Although vascular endothelial growth factor (VEGF) pathway inhibition has demonstrated activity in metastatic PPGL, prospective data evaluating selective VEGF receptor inhibition are limited. Axitinib is a potent, selective inhibitor of VEGFR-1, -2, and -3. We evaluated the efficacy and safety of axitinib in patients with progressive metastatic PPGL.
MethodsPatients with progressive metastatic or unresectable PPGL were enrolled in a prospective, open-label, single-arm, phase II study (NCT03839498). Eligible patients had measurable disease by RECIST version 1.1 and no prior treatment with a tyrosine kinase inhibitor. Axitinib was administered orally at an initial dose of 5 mg twice daily with protocol-defined dose modifications based on tolerability. The primary end points were objective response rate (ORR) and progression-free survival (PFS). Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE).
ResultsNineteen patients were enrolled, and 17 received study treatment and were evaluable for efficacy and safety. Six patients achieved a confirmed partial response, with an ORR of 35.3%. Median progression-free survival was 7.9 months (95% CI, 6.1-16.8 months), median duration of response was 7.4 months, median duration of treatment was 9.5 months, and median overall survival was 29 months. Hypertension, the most common treatment-related adverse event, occurred in 79% of patients, was effectively managed with antihypertensive therapy and dose modifications. Other common treatment-related adverse events included fatigue, diarrhea, oral mucositis, and palmar-plantar erythrodysesthesia. No patient permanently discontinued treatment because of treatment-related toxicity.
ConclusionsAxitinib demonstrated clinically meaningful antitumor activity in patients with progressive metastatic PPGL with a safety profile consistent with VEGF pathway inhibition and manageable with supportive care and dose modification. The observed activity was comparable to that reported with other VEGF-targeted therapies, including sunitinib. These findings support axitinib as a potential treatment option for patients with metastatic PPGL and warrant further evaluation.
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BibTeX
@misc{rivero2026axitinib,
title = {{Axitinib in Progressive Metastatic Pheochromocytoma and Paraganglioma: Results of a Phase II Study}},
author = {J. Del Rivero and A. Apolo and M. Edgerly and W. D. Figg and J. Lee and J. Ausiello and K. Pacak and S. E. Bates and T. Fojo},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.28.26364204},
url = {https://www.medrxiv.org/content/10.64898/2026.09.28.26364204v1},
note = {CC0},
}
RIS
TY - UNPB
TI - Axitinib in Progressive Metastatic Pheochromocytoma and Paraganglioma: Results of a Phase II Study
AU - J. Del Rivero
AU - A. Apolo
AU - M. Edgerly
AU - W. D. Figg
AU - J. Lee
AU - J. Ausiello
AU - K. Pacak
AU - S. E. Bates
AU - T. Fojo
PY - 2026
DA - 2026/09/28
PB - medRxiv
DO - 10.64898/2026.09.28.26364204
UR - https://www.medrxiv.org/content/10.64898/2026.09.28.26364204v1
AB - PurposeMetastatic pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine malignancies with limited systemic treatment options. Although vascular endothelial growth factor (VEGF) pathway inhibition has demonstrated activity in metastatic PPGL, prospective data evaluating selective VEGF receptor inhibition are limited. Axitinib is a potent, selective inhibitor of VEGFR-1, -2, and -3. We evaluated the efficacy and safety of axitinib in patients with progressive metastatic PPGL. MethodsPatients with progressive metastatic or unresectable PPGL were enrolled in a prospective, open-label, single-arm, phase II study (NCT03839498). Eligible patients had measurable disease by RECIST version 1.1 and no prior treatment with a tyrosine kinase inhibitor. Axitinib was administered orally at an initial dose of 5 mg twice daily with protocol-defined dose modifications based on tolerability. The primary end points were objective response rate (ORR) and progression-free survival (PFS). Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). ResultsNineteen patients were enrolled, and 17 received study treatment and were evaluable for efficacy and safety. Six patients achieved a confirmed partial response, with an ORR of 35.3%. Median progression-free survival was 7.9 months (95% CI, 6.1-16.8 months), median duration of response was 7.4 months, median duration of treatment was 9.5 months, and median overall survival was 29 months. Hypertension, the most common treatment-related adverse event, occurred in 79% of patients, was effectively managed with antihypertensive therapy and dose modifications. Other common treatment-related adverse events included fatigue, diarrhea, oral mucositis, and palmar-plantar erythrodysesthesia. No patient permanently discontinued treatment because of treatment-related toxicity. ConclusionsAxitinib demonstrated clinically meaningful antitumor activity in patients with progressive metastatic PPGL with a safety profile consistent with VEGF pathway inhibition and manageable with supportive care and dose modification. The observed activity was comparable to that reported with other VEGF-targeted therapies, including sunitinib. These findings support axitinib as a potential treatment option for patients with metastatic PPGL and warrant further evaluation.
ER -