Related Experiment Video
Updated: Feb 8, 2026
A Melanoma Patient-Derived Xenograft Model
Published on: May 20, 2019
Phase II study of pazopanib in combination with paclitaxel in patients with metastatic melanoma
John P Fruehauf1, Monica El-Masry2, Katherine Osann2
1Division of Hematology/Oncology, Chao Family Comprehensive Cancer Center, University of California, 101 The City Drive South, Bldg 56, Orange, Irvine, CA, 92868, USA. jfruehau@uci.edu.
Purpose:
This phase II study evaluated the safety and clinical activity of pazopanib, a potent and mutlitargeted tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptors (VEGFRs)-1, -2 and -3, platelet-derived growth factor receptor (PDGFR)-α and β, and cKit, in combination with metronomic paclitaxel in patients with metastatic melanoma.
Experimental Design:
Sixty chemotherapy-naive patients received pazopanib at a starting dose of 800 mg daily in combination with metronomic dosing of paclitaxel 80 mg/m2 weekly thrice every 4 weeks. The primary endpoint was 6-month progression-free survival (PFS) rate, while secondary endpoints included 1-year overall survival rate, RECIST response rates, progression-free survival rates and median overall survival. Prior BRAF-targeted therapy or checkpoint inhibitors were permitted.
Results:
The 6-month PFS rate was 68%, with a 1-year OS rate of 48%. Objective response rate was 37% comprising one complete and 20 partial responses. Stable disease at 8 weeks was noted in 32 patients (55%) with an overall clinical benefit rate of 93%. Six-month median progression-free survival was 8 months and median OS was 12.7 months. The most frequently (> 15%) reported non-hematologic, treatment-related adverse events were fatigue, diarrhea, hypertension, transaminitis and peripheral neuropathy. Treatment-related non-fatal bowel perforation, a known class effect, occurred in one patient. No significant association was noted between plasma levels of pazopanib and response.
Conclusions:
The combination of pazopanib and metronomic paclitaxel was well-tolerated, demonstrating significant activity in metastatic melanoma. Further evaluation of this combination is warranted.
Insights
Pazopanib combined with metronomic paclitaxel showed significant activity and was well-tolerated in metastatic melanoma patients. This combination therapy warrants further investigation for advanced skin cancer treatment.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Metastatic melanoma remains a significant challenge in cancer treatment.
- Targeted therapies and immunotherapies have improved outcomes, but novel combinations are needed.
Purpose of the Study:
- To evaluate the safety and clinical activity of pazopanib, a multi-targeted tyrosine kinase inhibitor, in combination with metronomic paclitaxel.
- To assess the efficacy of this combination in patients with metastatic melanoma.
Main Methods:
- A phase II study involving sixty chemotherapy-naive metastatic melanoma patients.
- Patients received pazopanib (800 mg daily) plus metronomic paclitaxel (80 mg/m² weekly).
- Primary endpoint: 6-month progression-free survival (PFS) rate; secondary endpoints: overall survival (OS), response rates.
Main Results:
- 6-month PFS rate was 68%, 1-year OS rate was 48%.
- Objective response rate (ORR) was 37% (1 complete, 20 partial responses).
- Clinical benefit rate was 93%; median PFS was 8 months, median OS was 12.7 months.
Conclusions:
- Pazopanib and metronomic paclitaxel combination is well-tolerated and demonstrates significant activity in metastatic melanoma.
- This combination therapy shows promise and warrants further clinical evaluation.
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