SUNY Downstate Medical Center, Brooklyn, NY
Michael Szarek , Michael N. Needle , Brian I. Rini , Sumanta K. Pal , David F. McDermott , Michael B. Atkins , Thomas E. Hutson , Bernard Escudier
Background: In the randomized phase III study TIVO-3, the VEGFR-TKI tivozanib (TIVO) increased progression-free survival with better tolerability but no difference in overall survival (OS) relative to sorafenib (SORA) as third- or fourth-line therapy in patients with metastatic RCC. These results provide motivation to apply quality-adjusted time without symptoms of disease and toxicity (Q-TWiST) methods to quantify the net health benefits of TIVO, in the presence of similar survival, when compared to SORA. Methods: In application of Q-TWiST, patient-level OS was subdivided into three mutually exclusive states: time with toxicity (TOX), time without symptoms and toxicity (TWiST), and time after progression/relapse (REL). Mean Q-TWiST was calculated by applying utility coefficients of 0.5, 1.0, and 0.5 to the restricted mean (max 36 months follow-up) health states of TOX, TWiST, and REL, respectively; 95% CIs for the means and mean differences were estimated by bootstrap distributions. Relative Q-TWiST gain was defined as the mean absolute Q-TWiST difference divided by the SORA mean OS. Results: Mean TWiST was significantly longer for TIVO than for SORA (10.30 months v.5.35 months; Table). Mean REL time was significantly shorter for TIVO, with no difference in mean TOX time. Mean Q-TWiST was 15.04 and 12.78 months for TIVO and SORA, respectively, a statistically significant difference (p=0.0493). The relative gain for TIVO was 11.2%. Clinical trial information: NCT02627963. Values in table are mean (95% CI) in months or p-value for difference in treatment group means. Conclusions: The difference in Q-TWiST in TIVO-3 was primarily driven by benefits of TIVO in TWiST, partially offset by superiority of SORA in REL time. As a third- or fourth-line treatment for RCC, TIVO significantly increased Q-TWiST relative to SORA, primarily through an increase in TWiST, which is generally considered to be the state with highest utility to patients. Consequently, Q-TWiST may be considered an alternative patient-centered measure of benefit of TIVO in these settings.
Health State | Tivozanib (n=175) | Sorafenib (n=175) | Difference | p-value |
---|---|---|---|---|
TOX | 1.29 (0.86, 1.81) | 1.15 (0.86, 1.51) | 0.14 (-0.45, 0.70) | 0.65 |
TWiST | 10.30 (8.32, 12.33) | 5.35 (4.42, 6.48) | 4.95 (2.56, 7.38) | <0.0001 |
REL | 8.18 (6.35, 10.18) | 13.71 (11.81, 15.59) | -5.53 (-7.84, -2.88) | <0.0001 |
Q-TWiST | 15.04 (13.36, 16.74) | 12.78 (11.56, 14.05) | 2.25 (0.01, 4.51) | 0.0493 |
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