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.
Authors: Beckermann Katy , Choueiri Toni K. , Motzer Robert J. , Barthelemy Philippe , Iacovelli Roberto , Emambux Sheik , Molina-Cerrillo Javier , Garmezy Benjamin , Barata Pedro C. , McKay Rana R. , Chehrazi-Raffle Alex , Hammers Hans J. , Heng Daniel Yick Chin , Braendle Edgar E. , Lebedinsky Claudia , Jin Bo , Albiges Laurence , McGregor Bradley Alexander 
Published: February 2025

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Background:
The TiNivo-2 study assessed TIVO 0.89 mg + NIVO vs TIVO 1.34 mg in patients with RCC that progressed after ICI therapy. This study did not meet its primary endpoint of demonstrating a benefit of adding NIVO to TIVO vs TIVO after prior ICI exposure; however, clinically meaningful outcomes were observed with TIVO as a second-line (2L) and third-line (3L) treatment following ICI. In the intent-to-treat population, the median progression-free survival was 5.7 months (95% CI, 4.0-7.4) with TIVO + NIVO and 7.4 months (5.6-9.2) with TIVO (hazard ratio, 1.10; 95% CI, 0.84-1.43;
P
=.49), with fewer treatment-emergent adverse events in the TIVO + NIVO vs TIVO arm. Quality of life (QOL) data are reported here (NCT04987203).
Methods:
The Functional Assessment of Cancer Therapy Kidney Cancer Symptom Index–Disease-Related Symptoms (FKSI-DRS) and European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaires were administered at baseline (BL), day 1 of each cycle, and end of treatment. The PRO-evaluable set was defined as all randomized patients with a BL and ≥1 post-BL assessment. Descriptive statistics were provided for the FKSI-DRS and EORTC QLQ-C30 data. The number and percentage of patients categorized as having improved (I), stable (S), or deteriorated (D) QOL were summarized.
Results:
As of April 1, 2024, median follow-up was 12.0 months. Median duration (range) of treatment was 6·3 months (2.68-10.12) with TIVO + NIVO and 7·4 months (2.83-11.04) with TIVO. Completion rates for FKSI-DRS and EORTC QLQ-C30 were >90% at BL and >50% at week 24 (≈6 mo.) in each arm. Compliance rates for both instruments at BL and week 24 were >90%. PRO results are presented in the table.
Conclusions:
There were no differences in the PRO outcomes between the combination therapy and monotherapy arms or between the 2 different TIVO doses. PRO data suggested that TIVO maintained the FKSI-DRS and EORTC QLQ-C30 mean scores from BL to week 24. In the TIVO arm, the proportion of patients who had improvement in FKSI-DRS and EORTC QLQ-C30 scores was numerically better in patients receiving 2L vs 3L treatment, while the portion of patients with a deterioration was smaller in the 2L than in the 3L. Clinical trial information:
NCT04987203
.

PRO variables
TIVO + NIVO
TIVO

ITT

2L

3L

ITT

2L

3L

FKSI-DRSBL mean (SD)
28.8 (5.6)
29.5 (4.9)
27.6 (6.5)
29.3 (5.3)
29.1(5.5)
29.5 (5.0)

Week 24 mean (SD)
29.9 (4.9)
30.1 (4.7)
29.5 (5.4)
29.4 (5.3)
29.3 (4.8)
29.6 (6.3)

I/S/D, %
28.2/47.2/24.6
28.0/52.7/19.4
28.6/36.7/34.7
22.9/53.5/23.6
27.5/53.8/18.7
15.1/52.8/32.1

EORTC-QLQ-C30BL mean (SD)
63.4 (23.4)
65.0 (21.8)
60.5 (26.1)
66.2 (21.4)
67.1 (21.9)
64.9 (20.7)

Week 24 mean (SD)
68.7 (17.4)
68.7 (16.1)
68.6 (20.6)
64.8 (21.1)
64.6 (20.7)
65.1 (22.4)

I/S/D, %
27.7/48.9/23.4
27.8/52.2/20.0
27.7/42.6/29.8
21.3/53.7/25.0
23.0/56.3/20.7
18.4/49.0/32.7