A quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis of nivolumab vs everolimus in advanced renal cell carcinoma (aRCC)

Abstract Background This analysis compared quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST) between nivolumab and everolimus among previously treated advanced renal cell carcinoma (aRCC) patients enrolled in the phase 3 CheckMate 025 trial (NCT01668784). Methods At 45-month follow-up, overall survival (OS) was partitioned into 3 health states: TWiST, time with grade ≥3 toxicity (TOX), and time after progression (REL). Mean Q-TWiST was determined by multiplying each state’s duration with its utility (TWiST, 1.0; TOX, 0.5; REL, 0.5). Relative Q-TWiST gains (calculated as Q-TWiST difference divided by everolimus OS) of ≥10% were predefined as clinically important. Immuno-oncology-specific sensitivity analyses considered 4 alternative progression definitions: Tumor size increase ≥25% from nadir; treatment discontinuation; ≥2-point reduction from baseline in Functional Assessment of Cancer Therapy-Kidney Symptom Index Disease-Related Symptoms scores; and a composite definition. A scenario incorporating grade ≥2 toxicities was tested. Results Compared to everolimus, nivolumab was associated with a significant Q-TWiST improvement of 3.3 months ( P Conclusions Nivolumab is associated with a statistically significant and clinically meaningful gain in quality-adjusted OS versus everolimus among previously treated aRCC patients.