Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA
Meredith M. Regan , Charlene Mantia , Lillian Werner , Ahmad A. Tarhini , Sumati Rao , Andriy Moshyk , Corey Ritchings , Jasmine I. Rizzo , Michael B. Atkins , David F. McDermott
Background: We previously defined a novel outcome, TFS, to characterize the time between ICI therapy cessation and subsequent therapy initiation/death. TFS is part of an integrated analysis to comprehensively describe how pts spend overall survival (OS) time, on and off treatment, with/without treatment-related toxicity. We reported survival states, including TFS, in ICI-treated pts with MEL in the phase 3 CheckMate 067 trial (NCT01844505) over the 36-mo period since randomization (Regan. J Clin Oncol. 2019); 60-mo results are presented here. Methods: Data were analyzed for 937 pts with MEL who started treatment with nivolumab (NIVO) plus ipilimumab (IPI), NIVO, or IPI in CheckMate 067. TFS was defined as the area between the Kaplan–Meier (KM) curves for 2 conventional time-to-event endpoints defined from randomization: time to protocol therapy cessation and time to subsequent therapy/death. TFS was also divided into TFS with/without grade ≥3 treatment-related adverse events (TRAEs), and OS was estimated. The area under each KM curve was estimated by the 60-mo restricted mean (r-mean) time to event and expressed as a percentage of the 60-mo period. Bootstrapped 95% CIs were calculated for differences. Results: Over the 60-mo period, pts spent an average of 33%, 17%, and 20% of time free of treatment after receiving NIVO+IPI, NIVO, and IPI, respectively (r-mean TFS, 19.7, 9.9, and 11.9 mo; Table). NIVO+IPI-treated pts had r-mean TFS that was 9.8 mo longer than NIVO-treated pts (95% CI, 6.7–12.8) and 7.8 mo longer than IPI-treated pts (95% CI, 4.6–11.0). Mean TFS with grade ≥3 TRAEs remained a small proportion of the 60-mo period at 3%, 2%, and < 1% with NIVO+IPI, NIVO, and IPI, respectively. Conclusions: With extended follow-up, average TFS with/without toxicity represented greater percentages of the 60-mo vs 36-mo period for NIVO+IPI and NIVO, but not for IPI. Pts treated with NIVO+IPI continued to have TFS twice as long as those treated with NIVO alone, due to earlier therapy cessation for toxicity without disease progression and subsequent resolution of many of those toxicities. The majority of TFS time was spent without grade ≥3 TRAEs across all arms.
Survival state | r-mean time (mo) | ||
---|---|---|---|
NIVO+IPI | NIVO | IPI | |
Time on protocol therapy | 12.3 | 16.9 | 2.6 |
TFS | 19.7 | 9.9 | 11.9 |
TFS without grade ≥3 TRAEs | 18.1 | 9.0 | 11.7 |
TFS with grade ≥3 TRAEs | 1.6 | 0.9 | 0.2 |
Survival after subsequent therapy initiation | 6.6 | 9.3 | 13.9 |
OS | 38.6 | 36.1 | 28.4 |
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