In patients with metastatic clear cell renal cell carcinoma (ccRCC), vascular endothelial growth factor receptors (VEGFR) and immune checkpoints are 2 of the main therapeutic targets. Researchers from France recently investigated the impact of duration of exposure to antiangiogenics on immunotherapy clinical outcomes in metastatic ccRCC.
A total of 354 patients were recruited from the NIVOREN trial, which examined the impact of nivolumab in patients with metastatic RCC who had progressed during or after prior systemic antiangiogenic regimens. Patients who had received nivolumab after only 1 prior antiangiogenic therapy were enrolled.
Response rate, clinical benefit, progression-free survival (PFS), and overall survival (OS) were analyzed based on the duration of first-line therapy (<6 months, ≥6 months) and in patients with long first-line exposure (≥18 months). Levels of 8 different plasma proteins and cytokines were recorded and compared based on first-line antiangiogenic duration.
A total of 127 (36%) patients received a first-line antiangiogenic for <6 months, while 227 (64%) received it for ≥6 months. The duration of first-line therapy was not associated with objective response to nivolumab (20.5% vs 23.9%; P=.50) or PFS (hazard ratio [HR], 0.92; P=.421). The median OS was 16.6 months in the <6 months subgroup and 31.3 months in the ≥6 months subgroup. Patients who had a longer treatment duration in the first-line setting had longer OS (HR, 0.73; P=.017).
Nivolumab activity in the second line is independent from first-line duration of VEGFR, but first-line VEGFR duration ≥6 months was associated with longer OS.