Active Therapy Improves Survival versus BSC After Disease Progression on Nivolumab and Cabozantinib

Nivolumab and cabozantinib are approved as monotherapies for patients with advanced renal-cell carcinoma (RCC). Nivolumab can be used in the second line and beyond, whereas cabozantinib is approved for all patients with advanced RCC. However, there is limited evidence regarding the optimal treatment approach after progression on both nivolumab and cabozantinib.¹

In this retrospective study, 42 patients with advanced RCC who had disease progression while receiving nivolumab and cabozantinib were enrolled from 8 Italian centers. Outcomes with active therapy were compared with outcomes with best supportive care (BSC). Overall survival (OS) was the primary end point. Overall response rate, progression-free survival, and OS for sorafenib versus everolimus were secondary end points.¹

After disease progression on nivolumab and cabozantinib, 42.9% and 57.1% of patients received BSC and active treatment, respectively. Of those patients who received active therapy, treatments included everolimus (28.6%), sorafenib (16.7%), sunitinib (4.8%), high-dose interleukin-2 (4.8%), and lenvatinib plus everolimus (2.4%). Most patients had clear-cell RCC (83%) and were intermediate or poor risk (85.7%). The median age was 65 years, and 76.2% of patients were male. The most common site of metastasis was lung in the overall population (73.8%), lung in those who received BSC (88.9%), and bone for those who received active treatment (70.8%). The most common treatment options were sunitinib in the first line (71.4%), nivolumab in the second line (64.3%), and cabozantinib in the third line (54.7%).¹

Median OS was longer in patients who received active treatment (13 months; 95% confidence interval, 4-not reached) compared with BSC (3 months; 95% confidence interval, 2-4; P = .001). When sorafenib was compared with everolimus, there was no significant difference in progression-free survival (5 vs 3 months, respectively; P = .5) or OS (not reached vs 13 months, respectively; P = .2). However, the rate of stable disease was higher with sorafenib than with everolimus (71.4% vs 16.7%, respectively; P = .03).¹

The researchers concluded that active treatment in late-line RCC after progression on nivolumab and cabozantinib confers a survival benefit versus BSC, with no significant advantage for the use of sorafenib or everolimus.¹

Reference

1. Giorgione R, Santini D, Stellato M, et al. Active therapy or best supportive care after disease progression to both nivolumab and cabozantinib in metastatic renal cell carcinoma: the BEYOND study (Meet-Uro 19). J Clin Oncol. 2021;39(suppl 6):Abstract 319.