The standard FDA-approved dosing of Fotivda (tivozanib) has demonstrated superior efficacy compared to reduced dosing in treating renal cell carcinoma (RCC), according to a comprehensive analysis presented at the 2025 ASCO Genitourinary Cancers Symposium. The study, which integrated data from three phase 3 trials - TIVO-1, TiNivo-2, and TIVO-3 - provides crucial insights into optimal dosing strategies for RCC treatment.
Dose-Response Relationship Findings
Dr. Bradley McGregor, Director of Clinical Research at Dana-Farber Cancer Institute's Lank Center of Genitourinary Oncology, presented compelling evidence showing a strong correlation between Fotivda exposure and clinical outcomes. Patients receiving higher concentrations of the drug demonstrated significantly better progression-free survival (PFS) rates. The analysis revealed a clear dose-response pattern:
- Highest exposure (62-177 ng/mL): 9.7 months median PFS
- Second quartile (47.9-62.0 ng/mL): 9.1 months median PFS
- Third quartile (38.4-47.9 ng/mL): 7.3 months median PFS
- Lowest exposure (13.9-38.4 ng/mL): 5.6 months median PFS
Tumor Response and Safety Profile
The study demonstrated a direct relationship between drug exposure and tumor response. Higher Fotivda concentrations corresponded to greater reductions in tumor size, with median best overall responses ranging from -23.8% in the highest exposure group to -7.02% in the lowest exposure group.
Notably, the analysis addressed safety concerns, particularly regarding hypertension - a common side effect of VEGFR TKI therapy. The incidence of hypertension, both overall and severe (grade 3), showed no significant difference between the standard 1.34mg dose and the reduced 0.89mg dose.
Combination Therapy Insights
The TiNivo-2 trial component, which evaluated Fotivda in combination with Opdivo (nivolumab), yielded several important findings. The lower 0.89mg dose of Fotivda used in combination therapy did not improve outcomes compared to the standard monotherapy dose. In fact, the combination therapy showed slightly inferior results, with a median PFS of 5.7 months versus 7.4 months for monotherapy.
Clinical Implications
These findings reinforce the FDA's original approval of Fotivda at 1.34mg for adults with relapsed or refractory advanced RCC following two or more prior systemic therapies. The recommended regimen remains at 1.34mg administered once daily for 21 consecutive days in a 28-day cycle, continuing until disease progression or unacceptable toxicity occurs.
Dr. McGregor emphasized that these exposure-response models clearly demonstrate the superior antitumor activity of the 1.34mg dose compared to 0.89mg, while maintaining a manageable safety profile. The data also suggests that attempting to reduce dose for combination therapy may not be necessary or beneficial.
