Estimating treatment-free survival (TFS) over extended follow-up in patients (pts) with advanced melanoma (MEL) treated with immune-checkpoint inhibitors (ICIs): Five-year follow-up of CheckMate 067.

Authors

null

Meredith M. Regan

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

Organizations

Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, Beth Israel Deaconess Medical Center, Boston, MA, Dana-Farber Cancer Institute, Boston, MA, H. Lee Moffitt Comprehensive Cancer Center and Research Institute, Tampa, FL, Bristol-Myers Squibb, Princeton, NJ, Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA

Research Funding

Pharmaceutical/Biotech Company
Bristol-Myers Squibb

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.

Estimated r-mean TFS time and survival states over 60-mo follow-up.

Survival stater-mean time (mo)
NIVO+IPINIVOIPI
Time on protocol therapy12.316.92.6
TFS19.79.911.9
TFS without grade ≥3 TRAEs18.19.011.7
TFS with grade ≥3 TRAEs1.60.90.2
Survival after subsequent therapy initiation6.69.313.9
OS38.636.128.4

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Abstract Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Poster Session

Session Title

Melanoma/Skin Cancers

Track

Melanoma/Skin Cancers

Sub Track

Advanced/Metastatic Disease

Citation

J Clin Oncol 38: 2020 (suppl; abstr 10043)

DOI

10.1200/JCO.2020.38.15_suppl.10043

Abstract #

10043

Poster Bd #

392

Abstract Disclosures