Axitinib in Progressive Metastatic Pheochromocytoma and Paraganglioma: Results of a Phase II Study
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Purpose
Metastatic 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.
Methods
Patients 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).
Results
Nineteen 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.
Conclusions
Axitinib 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.
