The latest findings from the phase 3 TiNivo-2 study reveal that adding Opdivo (nivolumab) to Fotivda (tivozanib) treatment maintains comparable patient-reported outcomes compared to Fotivda alone in patients with advanced clear cell renal cell carcinoma (RCC) who previously received systemic therapy.
Quality of Life Outcomes
The study evaluated patients who had progressed on one or two systemic therapies and at least one immune checkpoint inhibitor (ICI). Quality of life assessments utilized two validated instruments: the FKSI-DRS (Functional Assessment of Cancer Therapy Kidney Cancer Symptom Index-Disease-Related Symptoms) and EORTC QLQ-C30 questionnaires.
At week 24, the combination therapy group showed mean FKSI-DRS scores of 29.9 compared to 29.4 in the monotherapy arm, maintaining consistent levels from baseline scores of 28.8 and 29.3, respectively. Similarly, EORTC QLQ-C30 scores remained stable, with the combination arm showing scores of 68.7 versus 64.8 in the monotherapy group at week 24.
Treatment Line Analysis
Second-line treatment patients demonstrated particularly encouraging results. The combination therapy group showed mean FKSI-DRS scores of 30.1 at week 24, compared to 29.3 in the monotherapy arm. Dr. Kathryn Beckermann, lead study author from Vanderbilt School of Medicine, noted that improvements in quality of life scores were numerically greater in second-line versus third-line treatment patients receiving Fotivda monotherapy.
Clinical Efficacy and Safety Profile
The study enrolled 343 patients, with 171 receiving the combination therapy and 172 receiving Fotivda alone. Progression-free survival (PFS) analysis showed median PFS of 7.3 months for the combination versus 9.2 months for monotherapy in second-line treatment, while third-line treatment showed 4.8 months versus 5.5 months, respectively.
Safety analysis revealed that the combination therapy demonstrated lower rates of certain treatment-emergent adverse events, including:
- Fatigue (29% vs 40%)
- Nausea (16% vs 28%)
- Proteinuria (10% vs 18%)
- Vomiting (12% vs 21%)
However, some side effects were more prevalent in the combination arm, such as anemia (17% vs 9%) and pruritus (16% vs 6%). Researchers attribute the lower rates of certain VEGF tyrosine kinase inhibitor-associated side effects to reduced dosing in the combination therapy group.
Patient Response Categories
Overall response analysis showed that approximately 75% of patients across both treatment arms reported either improved or stable symptoms. Specifically:
- 28.2% of combination therapy patients showed improvement versus 22.9% in the monotherapy group
- 47.2% maintained stable symptoms in the combination arm compared to 53.5% in the monotherapy group
- Deterioration rates were similar at 24.6% versus 23.6% respectively
These findings suggest that adding Opdivo to Fotivda treatment maintains quality of life while potentially offering additional therapeutic benefits for advanced RCC patients who have progressed on previous treatments.
