TKI-Based Therapy Is Associated With Improved Disease Control in Metastatic Translocation RCC

A real-world analysis demonstrated TKI-based regimens were associated with higher disease control and longer treatment durability compared with dual immuno-oncology (IO) combinations or monotherapy in patients with metastatic translocation renal cell carcinoma (tRCC).

Data presented at the 2026 Kidney Cancer Research Summit showed that patients treated with a TKI-containing regimen in the first-line setting (n = 10) achieved an overall response rate (ORR) of 20% compared with 25% for patients treated with a non–TKI-containing regimen (n = 4; P = .80). The disease control rate (DCR) was 80% for the TKI group vs 25% for the non-TKI group (P = .05).

Covering all lines of therapy, TKI-based therapy (n = 18) produced an ORR of 27.8% and a DCR of 83.3%; these respective rates were 25.0% (P = .88) and 50.0% (P = .08) for patients treated without a TKI (n = 8).

In the first-line setting, the ORRs were 33% for dual IO regimens (n = 3), 17% for IO plus a TKI (n = 6), 100% for a TKI plus an mTOR inhibitor (n = 1), and 0% for monotherapy with either a TKI or IO agent (n = 4); the respective DCRs were 33%, 83%, 100%, and 50%. Across all lines of therapy, the ORRs 33% for dual IO (n = 6), 42.9% for IO plus TKI (n = 7), 66.7% for TKI plus an mTOR inhibitor (n = 3), and 0% for IO or TKI monotherapy (n = 10); the DCRs were 50%, 100%, 100%, and 60%, respectively.

“We evaluated outcomes of commonly used systemic therapies in metastatic tRCC across Mayo Clinic sites,” lead study author Oluwatayo Adeoye, MD, and colleagues wrote in a poster presentation of the data. “These findings are hypothesis-generating and support further evaluation of TKI-based treatment strategies in metastatic tRCC.”

Adeoye is a third-year fellow in the Division of Hematology and Medical Oncology in the Department of Medicine at Mayo Clinic in Jacksonville, Florida.

What is the trial about and who is eligible?

Prospective, randomized trials remain challenging due to the rarity and molecular heterogeneity of tRCC, which is a molecularly distinct subtype of RCC driven by MiT family gene fusions. Due to its rarity, evidence regarding the use of systemic therapy is limited, and the optimal treatment approach remains undefined. Thus, investigators sought to examine outcomes for patients with metastatic tRCC treated with standard-of-care regimens.

The real-world study included patients with pathologically confirmed tRCC treated across Mayo Clinic sites, whose data were retrospectively reviewed. Clinicopathologic, treatment, and radiographic response data were collected from the EMR.

Patients were grouped based on therapy received: dual IO, IO plus TKI, TKI plus mTOR inhibitor, and monotherapy. Along with assessing ORR and DCR, investigators examined time to next treatment (TTNT) within the subgroups.

Baseline characteristics for the overall population included a median age of 38 years (interquartile range [IQR], 31-56). Most patients were male (67%) and underwent prior nephrectomy (94%); notably, only 6% of patients had de novo metastatic disease. The median follow-up was 34.8 months (IQR, 16.4-58.7), covering a treatment period from 2011 to 2025. Fusion partners comprised MiT TFE3 (56%), MiT TFEB (17%), and other/unknown (28%).

What did the TTNT data show?

In the first-line setting, the median TTNT was 3.5 months for dual IO, 10.0 months for IO plus TKI, 10.2 months for TKI plus and mTOR inhibitor, and 8.4 months for monotherapy. Across all lines, these respective values were 6.0 months, not reached, 13.6 months, and 6.9 months.

Were there any study limitations?

Study authors pointed to the small sample size, due to the rarity of metastatic tRCC, limiting statistical power. The retrospective design with potential selection bias and treatment heterogeneity was also noted.

Reference

Adeoye O, Bolarinwa A, Jang A, et al. Outcomes of systemic therapy in metastatic translocation renal cell carcinoma (tRCC): a Mayo Clinic retrospective study. Presented at: Kidney Cancer Research Summit; July 23-24, 2026; Boston, MA. Abstract 26.