Pazopanib alternating with bevacizumab in patients with metastatic clear-cell renal cell carcinoma naive to treatment: a multicentre, single-arm, phase 1/2 trial.

In treatment-naive metastatic clear-cell renal cell carcinoma, alternating pazopanib with bevacizumab yields a median progression-free survival of 24·8 months after 63·7 months follow-up.

• Why it matters: VEGFR TKIs are the backbone for metastatic clear-cell renal cell carcinoma, but tolerability limits continuous dosing; scheduled bevacizumab breaks were hypothesized to improve both tolerability and outcomes versus historical controls.
• What they did: In a single-arm phase 1/2 trial across five US academic centers, phase 1 established an RP2D of pazopanib 800 mg daily (days 1–28) alternating with bevacizumab 10 mg/kg (days 36 and 50) on a 10-week cycle.
• The result: In phase 2, median progression-free survival was 24·8 months (95% CI 17·2–34·3) with grade 3–4 treatment-related hypertension in 34% (20/59) and no treatment-related deaths, supporting phase 3 confirmation.