Pazopanib as second-line antiangiogenic treatment in metastatic renal cell carcinoma after Tyrosine Kinase Inhibitor (TKI) failure: a phase 2 trial exploring immune-related biomarkers for testing in the post-immunotherapy/TKI era

Resumen:
Pazopanib is an oral angiogenesis tyrosine kinase inhibitor (TKI) recommended in metastatic renal cell carcinoma (mRCC) for treatment-naive 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 62 yr, 51.9% male). The objective overall response rate was 14.8% (95% confidence interval [CI] 1.4-28.2%). Median progression-free survival was 6.7 mo (95% CI 3.7-11.2) and median overall survival was 20.6 mo (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 6.0 mo (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.