Katy Beckermann, MD, PhD – Vanderbilt University
The phase 3 TiNivo-2 study (NCT04987203), sponsored by AVEO Pharmaceuticals, Inc., recently evaluated tivozanib (TIVO) combined with nivolumab (NIVO) versus TIVO monotherapy in patients with renal cell carcinoma (RCC) who progressed after immune checkpoint inhibitor (ICI) therapy. While the study didn’t meet its primary endpoint of improved progression-free survival (PFS) with the combination, it offers valuable insights into patient-reported outcomes (PROs) and treatment implications.
Study Design and Key Findings
Patients received either TIVO 0.89 mg + NIVO or TIVO 1.34 mg alone as second-line (2L) or third-line (3L) therapy. PFS results showed:
- TIVO + NIVO: Median PFS of 5.7 months (95% CI, 4.0-7.4)
- TIVO alone: Median PFS of 7.4 months (95% CI, 5.6-9.2)
- Hazard ratio: 1.10 (P = .49), suggesting no added benefit from NIVO.
Interestingly, the combination arm had fewer treatment-emergent adverse events, despite the lower TIVO dose. The study’s PRO data, collected via the FKSI-DRS and EORTC QLQ-C30 questionnaires, provide a deeper look at quality of life (QOL).
Quality of Life Results
As of April 1, 2024, with a median follow-up of 12 months, PRO completion rates were strong (>90% at baseline, >50% at week 24). Key takeaways:
- No QOL difference: Mean FKSI-DRS and EORTC QLQ-C30 scores remained stable from baseline to week 24 in both arms, with no significant differences between TIVO + NIVO and TIVO alone or between the two TIVO doses.
- Line of therapy trends: In the TIVO monotherapy arm, 2L patients showed numerically higher improvement rates (e.g., 27.5% improved FKSI-DRS vs 15.1% in 3L) and lower deterioration rates (e.g., 20.7% deteriorated EORTC QLQ-C30 vs 32.7% in 3L).
Table: PRO Highlights (ITT Population)
| Measure | TIVO + NIVO (ITT) | TIVO (ITT) |
|---|---|---|
| FKSI-DRS BL | 28.8 (SD 5.6) | 29.3 (SD 5.3) |
| FKSI-DRS Week 24 | 29.9 (SD 4.9) | 29.3 (SD 5.3) |
| I/S/D (%) | 28.2/47.2/24.6 | 22.9/53.5/24.6 |
| EORTC BL | 63.4 (SD 23.4) | 61.0 (SD 21.4) |
| EORTC Week 24 | 68.7 (SD 17.4) | 64.8 (SD 21.1) |
| I/S/D (%) | 27.7/48.9/23.4 | 21.3/53.7/25.0 |
What This Means for Renal Cell Carcinoma Treatment
The TiNivo-2 results challenge the assumption that adding an ICI like NIVO to a VEGFR inhibitor (TIVO) improves outcomes in renal cell carcinoma after prior ICI failure. TIVO monotherapy at 1.34 mg appears to offer a clinically meaningful PFS (7.4 months) with stable QOL, particularly in 2L settings. The lack of QOL decline across arms suggests TIVO is well-tolerated, but the data raise questions about optimal sequencing and combination strategies post-ICI.
Discussion Points
- Why might TIVO alone outperform the combination in PFS?
- How should stable QOL guide treatment choices in 2L vs 3L RCC?
- What factors could explain better PRO trends in 2L patients on TIVO?
For more details, check the full study results at ClinicalTrials.gov (NCT04987203). What are your thoughts on these findings? Share below!
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