Impact of Metastatic Site in Favorable-Risk Renal Cell Carcinoma Receiving Sunitinib or Pazopanib.

BACKGROUND: Although in metastatic renal cell carcinoma (mRCC) patients with intermediate and poor risk the benefit of combination strategies versus tyrosine kinase inhibitor (TKI) has been ascertained, in those with favorable risk data are ambiguous. Herein, we investigated the impact of number and type of metastatic site in patients with favorable risk to contribute to the best therapeutic choice. MATERIAL AND METHODS: Multicenter data regarding patients with favorable risk mRCC carcinoma receiving first-line TKIs, sunitinib or pazopanib, were retrospectively collected. We divided our population into 2 groups based on the number of metastatic sites and analyzed its impact on tumor response and efficacy outcome. The Kaplan-Meier method was used to estimate efficacy outcomes and the log-rank test to examine differences between subgroups. RESULTS: A total of 107 patients with a median age of 69 years were included in the final analysis. Patients with 1 metastatic site, compared with patients with > 1 site, had a significantly longer overall survival (OS) (not reached vs. 66 months) and a trend, although not statistically significant, of better progression-free survival (PFS) (31 vs. 17 months). In patients with 1 metastatic site, liver involvement was correlated with worse PFS and OS at the univariate analysis (P = .01) and was confirmed as independent poor prognostic factor for PFS at multivariate analysis. CONCLUSION: In conclusion, we reported a longer OS in favorable risk mRCC patients receiving TKI with only 1 metastatic site. Nevertheless, in patients with a single metastatic site, hepatic involvement correlated with worse PFS compared to other metastatic sites.

Tyrosine kinase and immune checkpoints inhibitors in favorable risk metastatic renal cell carcinoma: Trick or treat?

Over the past decade, the management of metastatic renal cell carcinoma (RCC) has undergone rapid evolution, culminating in a significant improvement in prognosis with frontline immunotherapy. RCC is a highly immunogenic and pro-angiogenic cancer, and mounting evidence has established the immunosuppressive effects of pro-angiogenic factors on the host's immune system. Anti-angiogenic agents such as tyrosine kinase inhibitors (TKIs) and bevacizumab, which obstruct the vascular endothelial growth factor pathway, have demonstrated the potential to enhance antitumor activity and improve the efficacy of immune checkpoint inhibitors (ICIs). Consequently, various combinations of TKIs and ICIs have been assessed and are currently considered the preferred regimens for all metastatic RCC patients, regardless of their prognostic risk score. Nevertheless, some inquiries have arisen within the medical community, as metastatic RCC patients with favorable risk scores who received ICIs and TKIs in combination showed no statistically significant advantage in overall survival compared to those treated with sunitinib alone. Considering these concerns, this review aims to elucidate the rationale behind TKI and ICI combination therapies, provide a summary of current first-line metastatic RCC combinations approved for use, with a focus on favorable-risk patients, and outline present challenges and future perspectives in this context.