Reducing Dose of First-Line TKI Improves Survival in Metastatic Renal Cell Carcinoma

Patients with metastatic renal cell carcinoma (RCC) who receive a reduced dose of the vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI) sunitinib or pazopanib in the first-line setting live longer than patients who receive the standard dose. This is according to a retrospective analysis of outcomes of 591 patients across 11 Italian centers that was recently published in Urologic Oncology. While all patients in this analysis began treatment at the standard dose of these agents, 45.7% received a reduced dose due to toxicity after a median treatment time of 3.6 months at the standard dose. Dose reductions were more commonly associated with patients who were older, had undergone nephrectomy, did not have metastatic disease at diagnosis, and who had favorable prognostic features.

Dose reduction of first-line treatment was associated with a significant improvement in unadjusted median overall survival (OS), from 24.0 months at standard dose to 49.4 months with reduced dose (HR 1.8, P<.001). The unadjusted median progression-free survival (PFS) was also improved with dose reduction (9.2 months vs 18.1 months; HR 1.74, P<.001). The benefit for dose reduction was seen across all patient subgroups, regardless of first-line treatment received, and was consistent even when correcting for positive prognostic features in the dose reduction group.

In the 45% of patients who received second-line therapy (TKIs or mTOR inhibitors), those who had received a reduced dose first-line lived an average of 8 months longer than those who received standard dose first-line (unadjusted median OS from start of second-line therapy, 19.8 months vs 11.8 months, P = .007). This benefit was independent of class of therapy selected for second-line treatment.

The authors concluded that this study demonstrated that reduced dose of first-line therapy with sunitinib or pazopanib for metastatic RCC does not adversely impact outcomes and may, in fact, serve as a positive prognostic factor. While these results should be verified prospectively, they may help refine decision-making for first-line treatment of metastatic RCC in the future.


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