We compared quality-adjusted survival (OS) of combined NIVO+IPI or NIVO alone vs IPI among treatment-naïve pts with advanced MEL enrolled in the CheckMate 067 trial.
The Q-TWiST approach was used to partition OS into 3 health states: time without disease progression or symptoms of toxicity (TWiST), time with grade ≥3 treatment-related AE toxicity after randomization but before progression (TOX), and time after progression (REL). Q-TWiST was calculated by multiplying mean time spent in each state at 36 months (mos) by their utility (TWiST=1.0, TOX=0.5, and REL=0.5). Q-TWiST differences were assessed at various times ranging from 3 to 36 mos. A ≥ 15% relative Q-TWiST gain (vs mean IPI OS) was considered clearly clinically important.
Compared with IPI, NIVO+IPI pts had longer (difference in mean mos, 95% CI) TWiST (9.6, 7.4 to 11.7) and TOX (0.3, 0.1 to 0.4) but shorter REL time (-5.2, -7.1 to -3.2). Compared with IPI, NIVO pts had a longer TWiST (7.3, 5.0 to 9.6), shorter REL time (-3.4, -5.5 to -1.3), and shorter TOX (-0.1, -0.2 to 0.1). Q-TWiST was highest for NIVO+IPI, followed by NIVO, and IPI (Table). Relative Q-TWiST gains were also favorable for NIVO+IPI (+34.0% v IPI) and NIVO (+26.4% v IPI) and increased as follow-up increased from 3 to 36 months for all comparisons.
At 36 months, NIVO and NIVO+IPI pts had a clinically important improvement in Q-TWiST vs IPI. As these benefits continue to accrue over time, future analyses with longer follow-up are planned.Table:
|Mean (95% CI) time, mos|
|NIVO+IPI (n = 314)||NIVO (n = 316)||IPI (n = 315)|
|TOX||0.6 (0.4 to 0.7)||0.2 (0.1 to 0.3)||0.3 (0.2 to 0.4)|
|TWiST||19.1 (17.4 to 20.8)||16.8 (15.1 to 18.5)||9.5 (8.1, 10.9)|
|REL||6.1 (4.7 to 7.6)||7.9 (6.5 to 9.3)||11.3 (9.8 to 12.8)|
|Q-TWiST||22.4 (21.0 to 23.9)||20.9 (19.4 to 22.3)||15.3 (14.1 to 16.5)|
Clinical trial identification
QoL study based on the 067 trial NCT01844505 protocol number is CA209-067 (CheckMate 067)
Legal entity responsible for the study
M. Botteman: Employed by and owns stock in Pharmerit International. Pharmerit International has received research funding from BMS to conduct this research. Pharmerit International is a global health economics and outcomes research consulting firm that receives researching funding and fees related to consulting and other advisory roles from numerous private organizations from the pharmaceutical, biotech, device, and medical industry. R. Shah, L. Luo: Employed by Pharmerit International. Pharmerit International has received research funding from BMS to conduct this research. K. Gupte-Singh, J. Sabater, S. Rao: Employed by and owns stock in Bristol-Myers Squibb. D.F. McDermott: David McDermott served as a consultant or advisor for Pfizer and Genentech. M.B. Atkins: Served as a consultant or advisor for GNE, Pfizer, Novartis, GSK, C-Cam, X4 Pharma, Amgen, Lilly, Alkermes, Infinity Pharmaceuticals, Genoptix, Bristol-Myers Squibb, Nektar, Merck; received honoraria from Bristol-Myers Squibb. All other authors have declared no conflicts of interest.