Tivozanib Preserves QOL From Baseline to Week 24 in ICI-Pretreated RCC

Patients with renal cell carcinoma (RCC) who had previously received immune checkpoint inhibitor (ICI) therapy reported similar quality of life (QOL) outcomes regardless of whether they received tivozanib (Fotivda) monotherapy or a reduced dose of tivozanib in combination with nivolumab (Opdivo) in the phase 3 TiNivo-2 trial (NCT04987203), according to Katy Beckermann, MD, PhD.

Previously reported findings from TiNivo-2 demonstrated that ICI rechallenge with nivolumab plus tivozanib did not improve efficacy outcomes vs tivozanib monotherapy in patients with advanced RCC who had progressed following treatment with 1 or 2 lines of therapy, including an ICI.1,2 In the intent-to-treat (ITT) population, the median progression-free survival (PFS) was 5.7 months (95% CI, 4.0-7.4) with tivozanib plus nivolumab (n = 171) vs 7.4 months (95% CI, 5.6-9.2) with tivozanib monotherapy (n = 172; HR, 1.10; 95% CI, 0.84-1.43; P = .49). Median follow-up was 11.8 months in the combination arm and 12.5 months in the monotherapy arm.

Patient-reported outcomes (PROs) from this trial were presented at the 2025 Genitourinary Cancers Symposium.3 Among patients in the ITT population who received tivozanib plus nivolumab, the mean Functional Assessment of Cancer Therapy Kidney Cancer Symptom Index–Disease-Related Symptoms (FKSI-DRS) score was 28.8 (standard deviation [SD], 5.6) at baseline vs 29.9 (SD, 4.9) at week 24. In this population, the mean European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 score was 63.4 (SD, 23.4) at baseline vs 68.7 (SD, 17.4) at week 24. Among patients in the ITT population who received tivozanib alone, the FKSI-DRS scores at these respective time points were 29.3 (SD, 5.3) and 29.4 (SD, 5.3); the respective EORTC-QLQ-C30 scores were 66.2 (SD, 21.4) and 64.8 (SD, 21.1).

However, a greater proportion of patients treated with tivozanib monotherapy in the second-line setting had numerically improved FKSI-DRS (27.5%) and EORTC-QLQ-C30 (23.0%) scores compared with those who received this agent as third-line treatment (FKSI-DRS, 15.1%; EORTC-QLQ-C30, 18.4%). Additionally, fewer patients in the second-line population reported deterioration in FKSI-DRS (18.7%) and EORTC-QLQ-C30 (20.7%) scores compared with those in the third-line population (FKSI-DRS, 32.1%; EORTC-QLQ-C30, 32.7%).

“Based on these patient QOL data, tivozanib performed in a way that allowed patients to still have great QOL during treatment,” Beckermann said in an interview with OncLive® during the meeting. “That’s important in the refractory setting when we’re considering sequencing TKI therapies. These were nice data to see.”

In the interview, Beckermann, an instructor in medicine in the Rathmell Lab and the chief academic fellow in the Division of Hematology/Oncology at the Vanderbilt School of Medicine in Nashville, Tennessee, discussed the rationale for, design of, and key findings from this PRO analysis.

OncLive: Why was the combination of tivozanib and nivolumab hypothesized to provide clinical benefit in patients with RCC who had progressed after ICI therapy?

Beckermann: There’s always hope that IO [immuno-oncology (therapy)] will provide durable benefit, so without the [TiNivo-2] data, many [of us] were continuing IO therapy after progression on frontline PD-1 inhibitor–based regimens. TiNivo-2 was a great study. It enabled us to test this hypothesis by comparing tivozanib at a dose of 0.89 mg in combination with nivolumab vs the control arm of full-dose tivozanib at 1.34 mg.

Previously reported data from TiNivo-2 showed that the study did not meet its primary end point of benefit with the addition of nivolumab to tivozanib. How did tivozanib perform in this trial following prior ICI treatment?

This study was extremely informative, although it was a negative study and proved that we should not continue IO after progression on frontline IO. However, it also gave us context for how tivozanib performed. Some patients received tivozanib in the second-line setting, having received only 1 prior treatment line, and for other patients, [tivozanib] was their third-line treatment. In the ITT population, the median PFS for tivozanib alone was 7.4 months compared with 5.7 months [with the addition of nivolumab]. In the second-line population, patients in the tivozanib-alone arm had a median PFS of 9.2 months compared with 7.3 months in the tivozanib plus nivolumab arm.

How was patient-reported QOL evaluated in this analysis?

An important question that we should consider is: How is patient QOL in the refractory setting? If we’re dose intensifying or adding treatment regimens, is that going to add toxicity? Does that affect QOL?

This was an exploratory end point in the clinical trial using 2 different metrics: the EORTC-QLQ-C30 questionnaire and FKSI-DRS questionnaire. Across the treatment arms, [these questionnaire answers were] taken at baseline and at day 1 of every cycle. The completion rates were equivalent between the arms. From that, we tried to assess the QOL metrics. [Treatment with] tivozanib kept these QOL measures even from the beginning to the end of the study, based on both the FKSI-DRS and EORTC-QLQ-C30 questionnaires.

What were the QOL outcomes between the 2 study arms, as well as between patients who received treatment in the second- vs third-line settings?

There was no difference between the arms regarding QOL. That was excellent to see. However, [keeping in mind that] these are smaller numbers, it seems there was a trend toward improvement on the EORTC-QLQ-C30 and FKSI-DRS models for patients who received therapy in the second-line setting compared with in the third-line setting. [Additionally, fewer patients had] a deterioration in QOL metrics [when they received treatment] in the second-line setting vs the third-line setting.

References

1. Choueiri TK, Motzer RJ, Beckermann K, et al. Tivozanib–nivolumab vs tivozanib monotherapy in patients with renal cell carcinoma (RCC) following 1 or 2 prior therapies including an immune checkpoint inhibitor (ICI): results of the phase III TiNivo-2 study. Ann Oncol. 2024;35(suppl 2):S1261-S1262. doi:10.1016/j.annonc.2024.08.2316
2. Choueiri TK, Albiges L, Barthélémy P, et al. Tivozanib plus nivolumab versus tivozanib monotherapy in patients with renal cell carcinoma following an immune checkpoint inhibitor: results of the phase 3 TiNivo-2 study. Lancet. 2024;404(10460):1309-1320. doi:10.1016/S0140-6736(24)01758-6
3. Beckermann K, Choueiri T, Motzer R, et al. Patient-reported outcomes (PROs) for tivozanib (TIVO) + nivolumab (NIVO) vs TIVO monotherapy in patients with renal cell carcinoma (RCC) following an immune checkpoint inhibitor (ICI): results of the phase 3 TiNivo-2 study. J Clin Oncol. 2025;43(suppl 5):459. doi:10.1200/JCO.2025.43.5_suppl.459