Second-line cabozantinib shows efficacy in advanced renal cell carcinoma

Second-line cabozantinib (Cabometyx) with or without atezolizumab (Tecentriq) demonstrated efficacy and manageable safety in patients with advanced renal cell carcinoma (RCC) who progressed following treatment with an immunotherapy-based regimen, according to data from a subgroup analysis of the phase 3 CONTACT-03 trial (NCT04338269).¹

Data also showed that efficacy with cabozantinib was observed regardless of whether patients received a dual immuno-oncology (IO) combination or an IO plus tyrosine kinase inhibitor (TKI) in the first-line setting.

The safety profile of cabozantinib with or without atezolizumab was also consistent regardless of prior IO regimen.

The findings were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

In total, 129 patients randomly assigned to cabozantinib plus atezolizumab and 107 patients randomly assigned to cabozantinib alone had received prior treatment with any IO regimen. Of these, 80 vs 70 patients in each arm received a prior IO-IO combination, and 49 vs 37 patients in each arm received a prior IO-TKI regimen, respectively.

Among patients who received any IO regimen, the median progression-free survival (PFS) was 10.2 months (95% CI, 8.0 to 12.5) in the cabozantinib plus atezolizumab arm vs 10.2 months (95% CI, 8.3 to 10.6) in the cabozantinib alone arm (HR, 1.03; 95% CI, 0.75 to 1.41; P = .8746). The PFS rates at 6-, 12-, and 18-months were 73.6% vs 69.6%, 38.0% vs 44.6%, and 22.6% vs 30.1%, respectively.

In patients who received a dual IO regimen in the first-line setting, the median PFS was 10.4 months (95% CI, 8.3 to 12.7) in the cabozantinib plus atezolizumab arm vs 10.5 months (95% CI, 8.1 to 14.0) in the monotherapy arm (HR, 1.01; 95% CI, 0.67 to 1.51; P = .9806). The PFS rates in both arms at 6-, 12-, and 18-months were 77.8% vs 70.0%, 42.6% vs 47.7%, and 27.9% vs 33.3%, respectively.

Further, in patients who received an IO-TKI combination, the median PFS was 10.2 months (95% CI, 7.1 to 10.5) in the cabozantinib plus atezolizumab arm vs 10.4 months (95% CI, 6.3 to 12.5) in the cabozantinib alone arm (HR, 10.6; 95% CI, 0.64 to 1.77; P = .8150). The respective 6-, 12-, and 18-month PFS rates were 66.9% vs 68.7%, 30.0% vs 38.8%, and 13.7% vs 24.1%.

Median overall survival (OS) was also comparable across treatment arms.

In patients who received any IO combination, the median OS was 24.3 months (95% CI, 20.2 to not estimable [NE]) in the combination arm and NE (95% CI, 18.3 to NE) in the monotherapy arm (HR, 0.82; 95% CI, 0.54 to 1.26; P = .3684). The 6-, 12-, and 18-month OS rates were 89.0% vs 88.4%, 75.5% vs 67.7%, and 64.0% vs 61.4%, respectively.

Among patients who received a prior IO-IO regimen, median OS was 24.3 months (95% CI, 19.2 to NE) in the combination arm vs NE (95% CI, 16.5 to NE) in the monotherapy arm (HR, 0.77; 95% CI, 0.45 to 1.30; P = .3222). The respective OS rates at 6-, 12-, and 18-months were 92.3% vs 86.9%, 79.3% vs 65.6%, and 65.0% vs 59.6%.

Additionally, in those who received a prior IO-TKI, the median OS was NE (95% CI, 17.1 to NE) in the combination arm vs 20.7 months (95% CI, 15.3 to NE) in the monotherapy arm (HR, 0.92; 95% CI, 0.45 to 1.86; P = .8078). The respective OS rates were 83.7% vs 91.5%, 69.4% vs 71.5%, and 63.1% vs 64.6% at 6-, 12-, and 18-months, respectively.

The safety profile of cabozantinib with or without atezolizumab was also consistent regardless of prior IO regimen. Overall, grade 3 to 4 treatment-related adverse events (TRAEs) occurred in 58% of patients in the combination arm vs 48% of patients in the monotherapy arm. Serious TRAEs were reported in 25% and 13% of patients, respectively.

AEs led to dose modifications in 92% of patients in the cabozantinib plus atezolizumab arm vs 87% of patients in the monotherapy arm. Further, 17% and 5% of patients, respectively, discontinued treatment due to AEs.

“Results from this post-hoc subgroup analysis of CONTACT-03 suggest [second-line cabozantinib] is effective in patients with advanced RCC previously treated with [first-line] IO-IO or IO-TKI regimens,” the authors concluded. “These results can inform clinicians making [second-line] treatment decisions for patients who have progressed on contemporary [first-line] IO-containing combinations.”

REFERENCE

1. Suárez C, Choueiri TK, Albiges L, et al. Efficacy and safety of second-line cabozantinib ± atezolizumab for patients with advanced renal cell carcinoma after progression on immuno-oncology combinations: Subgroup analysis of CONTACT-03. J Clin Oncol. 2025;43(suppl 17):4523. doi:10.1200/JCO.2025.43.16_suppl.4523