Clinical Outcomes of Sequential Cabozantinib and Axitinib After First-Line Nivolumab Plus Ipilimumab in Advanced Renal Cell Carcinoma: A Single-Center Exploratory Study.

BACKGROUND

Evidence regarding sequential vascular endothelial growth factor receptor tyrosine kinase inhibitor therapy after first-line nivolumab plus ipilimumab in advanced renal cell carcinoma (RCC) remains limited. This exploratory study described the clinical outcomes of sequential cabozantinib and axitinib administered as second- and third-line therapy, with additional analyses according to treatment order and early progressive disease (PD) status.

PATIENTS AND

METHODS

We retrospectively reviewed 12 patients with advanced RCC who sequentially received cabozantinib and axitinib as second- and third-line therapy after first-line nivolumab plus ipilimumab between September 2018 and January 2026. Patients were categorized into cabozantinib-to-axitinib (n=8) and axitinib-to-cabozantinib (n=4) groups. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors version 1.1. Combined time to treatment failure (TTF) was measured from second-line initiation to progression during third-line therapy or death; event-free patients were censored at last follow-up.

RESULTS

Among patients receiving second-line cabozantinib, three (37.5%) had stable disease and five (62.5%) had PD; among those receiving axitinib, three (75.0%) had a partial response and one (25.0%) had stable disease. Median second-line TTF was 5.1 months (interquartile range [IQR], 2.6-8.6) with cabozantinib and 10.1 months (IQR, 8.9-10.4) with axitinib (p=0.154). Median third-line TTF was 3.0 months (IQR, 1.6-13.6) with cabozantinib and 3.5 months (IQR, 2.7-5.7) with axitinib (p=0.808). Median combined TTF was 14.2 months for axitinib-to-cabozantinib and 10.4 months for cabozantinib-to-axitinib (p=0.359), and 8.3 versus 13.9 months in patients with early versus non-early PD (p=0.113).

CONCLUSION

Sequential cabozantinib and axitinib therapy after nivolumab plus ipilimumab was feasible in selected patients with advanced RCC. Given the small exploratory cohort, no firm conclusion regarding the comparative efficacy of the two sequences can be drawn. Patients with early PD showed a numerical trend toward shorter combined TTF, although this comparison was statistically inconclusive.