Joaquim Bellmunt1, Emilio Esteban2, Xabier García Del Muro3, Juan Manuel Sepúlveda4, Pablo Maroto5, Enrique Gallardo6, Aranzazu González Del Alba7, Olatz Etxaniz8, Marta Guix9, Jose Luis González Larriba10, Jose A Arranz11, Miriam Redrado12, Alfonso Calvo12. 1. University Hospital del Mar, Barcelona, Spain. Electronic address: jbellmunt@parcdesalutmar.cat. 2. Hospital Universitario Central de Asturias, Oviedo, Spain. 3. Instituto Catalán de Oncología, IDIBELL, Barcelona, Spain. 4. Hospital Universitario 12 de Octubre, Madrid, Spain. 5. Hospital de Sant Pau, Barcelona, Spain. 6. Institut d'Investigació i Innovació Parc Taulí, Parc Taulí Hospital Universitari, Barcelona, Spain. 7. Servicio de Oncologia Médica, Hospital Universitario Son Dureta, Palma de Mallorca, Spain. 8. Instituto Catalán de Oncología, Badalona, Spain. 9. University Hospital del Mar, Barcelona, Spain. 10. Hospital Clínico San Carlos, Madrid, Spain. 11. Hospital Gregorio Marañón, Madrid, Spain. 12. CIBERONC/IDISNA Program of Solid Tumours and Biomarkers, CIMA and Department of Histology and Pathology, School of Medicine, University of Navarra, Pamplona, Spain.
Abstract
Pazopanib is an oral angiogenesis tyrosine kinase inhibitor (TKI) recommended in metastatic renal cell carcinoma (mRCC) for treatment-naïve patients or those experiencing cytokine failure. We conducted a phase 2, open-label, single-arm study in ten Spanish centres among mRCC patients whose disease progressed on first-line TKI. Patients received pazopanib until disease progression, death, or unacceptable toxicity. Twenty-seven patients were included (median age 62yr, 51.9% male). The objective overall response rate was 14.8% (95% confidence interval [CI] 1.4-28.2%). Median progression-free survival was 6.7mo (95% CI 3.7-11.2) and median overall survival was 20.6mo (95% CI 12.6-27.4). Lower circulating levels of IL-10 (p=0.002) were observed in responding patients at 8 wk after treatment. The median pazopanib treatment duration was 6.0mo (range 1.0-47.0). Most patients (48.1%) had mild or moderate adverse events (AEs), while 44.4% had severe AEs. Pazopanib was clinically active and well tolerated as a second-line treatment in mRCC patients after TKI failure, and circulating IL-10 levels could predict response. PATIENT SUMMARY: Pazopanib could be used as a second-line therapy for the treatment of metastatic renal cell carcinoma after failure of tyrosine kinase inhibitor (TKI) therapy when drugs such as nivolumab and cabozantinib are not available. Now that immunotherapy plus antiangiogenic therapy is a first-line option, IL-10 levels deserve further exploration as a potential predictor of response to sequential TKI-TKI therapy.
Pazopanib is an oral angiogenesis tyrosine kinase inhibitor (TKI) recommended in metastatic renal cell carcinoma (mRCC) for treatment-naïve patients or those experiencing cytokine failure. We conducted a phase 2, open-label, single-arm study in ten Spanish centres among mRCC patients whose disease progressed on first-line TKI. Patients received pazopanib until disease progression, death, or unacceptable toxicity. Twenty-seven patients were included (median age 62yr, 51.9% male). The objective overall response rate was 14.8% (95% confidence interval [CI] 1.4-28.2%). Median progression-free survival was 6.7mo (95% CI 3.7-11.2) and median overall survival was 20.6mo (95% CI 12.6-27.4). Lower circulating levels of IL-10 (p=0.002) were observed in responding patients at 8 wk after treatment. The median pazopanib treatment duration was 6.0mo (range 1.0-47.0). Most patients (48.1%) had mild or moderate adverse events (AEs), while 44.4% had severe AEs. Pazopanib was clinically active and well tolerated as a second-line treatment in mRCC patients after TKI failure, and circulating IL-10 levels could predict response. PATIENT SUMMARY: Pazopanib could be used as a second-line therapy for the treatment of metastatic renal cell carcinoma after failure of tyrosine kinase inhibitor (TKI) therapy when drugs such as nivolumab and cabozantinib are not available. Now that immunotherapy plus antiangiogenic therapy is a first-line option, IL-10 levels deserve further exploration as a potential predictor of response to sequential TKI-TKI therapy.