Patient-Reported Outcomes From TiNivo-2 Highlight Quality-of-Life Considerations in RCC Treatment

A new analysis from the phase III TiNivo-2 study, presented by Katy Beckermann, MD, of Tennessee Oncology, during the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium, explored patient-reported outcomes (PROs) among patients with renal cell carcinoma (RCC) treated with tivozanib alone or in combination with nivolumab after disease progression during treatment with immune checkpoint inhibitors (ICIs). Although the study did not meet its primary endpoint of demonstrating an efficacy advantage for the combination over tivozanib monotherapy, patient-reported quality-of-life (QOL) assessments suggest that tivozanib maintained functional and symptom control over the course of treatment.

Many patients with RCC treated with ICIs eventually experience disease progression, necessitating effective second-line (2L) and third-line (3L) treatment options. TiNivo-2 was designed to evaluate whether adding nivolumab to tivozanib could improve outcomes in this post-ICI setting. Although the combination did not show a statistically significant progression-free survival benefit over tivozanib alone, PRO assessments provide important insights into the patient experience with these treatments.

The TiNivo-2 study evaluated health-related QOL using two validated instruments: the Functional Assessment of Cancer Therapy Kidney Cancer Symptom Index–Disease-Related Symptoms (FKSI-DRS) and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). These assessments measured patients’ symptoms, functional well-being, and overall treatment burden.

The study enrolled patients with advanced RCC that had progressed after ICI therapy. Participants were randomized to receive either tivozanib (0.89 mg) plus nivolumab or tivozanib monotherapy (1.34 mg). Patient-reported outcomes were assessed at baseline, on the first day of each treatment cycle, and at the end of treatment. Patients were categorized based on their treatment line (2L vs 3L), and their QOL status was classified as improved, stable, or deteriorated over time.

As of April 1, 2024, the median follow-up was 12 months. The median treatment duration was 6.3 months in the combination arm and 7.4 months in the monotherapy arm. Completion rates for FKSI-DRS and EORTC QLQ-C30 exceeded 90% at baseline and remained above 50% at 24 weeks, demonstrating robust data collection.

The study found no significant differences in PROs between the two treatment arms. Tivozanib, whether alone or combined with nivolumab, maintained mean FKSI-DRS and EORTC QLQ-C30 scores from baseline through 24 weeks. Patients in both groups generally reported stable symptom burden and functional well-being throughout treatment.

In the tivozanib monotherapy group, a greater proportion of patients receiving 2L therapy reported QOL improvements compared with those receiving 3L therapy. Conversely, deterioration rates were higher in the 3L population, suggesting that earlier intervention with tivozanib may provide better symptom control and overall well-being.

The FKSI-DRS results showed that in the combination arm, 28.2% of patients reported improvement, 47.2% remained stable, and 24.6% experienced deterioration. In the monotherapy arm, 22.9% reported improvement, 53.5% remained stable, and 23.6% experienced deterioration. Similar trends were observed in the EORTC QLQ-C30 scores, where patients in both arms experienced overall stability in QOL measures.

Clinical Implications and Future Directions

Although TiNivo-2 did not demonstrate a clear clinical benefit of adding nivolumab to tivozanib for patients with RCC in the post-ICI setting, the PRO data suggest that tivozanib remains a well-tolerated treatment option that maintains QOL over time. The findings indicate that patients treated in the 2L setting may derive more symptom relief and functional stability compared with those receiving tivozanib as a 3L therapy.