Abstract 1456P
Background
Long-term (minimum 60-month) follow-up from the CheckMate 214 study showed high OR rate (42%) and durable response benefits with a yet to be reached median duration of response (DoR) for I/P risk aRCC patients treated with N+I. This led to sustained survival plateaus implying the possibility of long-term survivors (LTS), which can be estimated via mixture cure models (MCMs).
Methods
MCMs were applied to model OS and DoR separately for I/P risk patients achieving OR with N+I in the trial. In both analyses, LTS were only subject to risk of non-disease-related (NDR) mortality (who also remained in response until death in DoR analysis), whereas non-LTS were subject to extra disease-related risk for their OS/DoR which were modeled via parametric distributions. Age- and gender-specific NDR mortality rates were obtained from the UK Office of National Statistics. Patient-level data from the trial were used to simultaneously estimate the fraction of LTS and OS/DoR for non-LTS through maximum likelihood methods. Candidate models were evaluated based on statistical fit criteria and their visual fits to the observed response and hazard trends in the trial. Auxiliary analyses explored the association of estimated fraction of LTS with age, gender, risk group, Karnofsky performance status and prior nephrectomy/radiotherapy using progression-free survival data of the entire I/P risk patients treated with N+I.
Results
Estimated proportion of LTS among the responders was 72.8% [95% CI: 63.3%-80.5%] from the best-fitting model (log-normal) to the OS data and 58.9% [95% CI: 48.8%-68.4%] from the best-fitting model (log-normal) to the DoR data. Ranges of estimated proportion of LTS were narrow across all candidate models: 72.8%-74.3% in OS analysis and 58.4%-61.0% in DoR analysis. No statistically significant association was observed between estimated proportions of LTS and the covariates.
Conclusions
OR to N+I is associated with higher estimated likelihood of long-term survivorship. Robustness of the results with respect to model choice indicate that MCMs can adequately capture the long-term trend and the underlying heterogeneity in the survival of the responders.
Clinical trial identification
CheckMate 214: NCT02231749.
Editorial acknowledgement
Legal entity responsible for the study
The authors of the study on behalf of Bristol Myers Squibb.
Funding
Bristol Myers Squibb.
Disclosure
S. George: Financial Interests, Personal, Advisory Board, advisor/consultant: BMS, Bayer, pfizer, Exelixis, Corvus, Sanofi/ Genzyme, Seattle Genetics, EMD Serono, Eisai, Merck, Aveo, QED therapeutics; Financial Interests, Institutional, Invited Speaker: Pfizer, Merck, Agensys, Novartis, BMS, Bayer, Eisai, Seattle Genetics, Calithera, Corvus, Surface Oncology, Exelixis, Aravive, Aveo, Gilead. M. Hunger: Financial Interests, Institutional, Research Grant, Received funds from Bristol Myers Squibb to conduct this research: Bristol Myers Squibb; Financial Interests, Personal, Full or part-time Employment, Employee of ICON plc: ICON. O. Hughes: Financial Interests, Institutional, Research Grant, Received funds from Bristol Myers Squibb to conduct this research: Bristol Myers Squibb; Financial Interests, Personal, Full or part-time Employment, yee of ICON plcEmplo: ICON. J.R. May: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. M. Dyer: Financial Interests, Personal, Stocks/Shares, Owns restricted shares of Bristol Myers Squibb: Bristol Myers Squibb; Financial Interests, Personal, Project Lead, Leading projects within Bristol Myers Squibb as an employee of the company: Bristol Myers Squibb; Financial Interests, Personal, Full or part-time Employment, Employee of Bristol Myers Squibb: Bristol Myers Squibb. F. Ejzykowicz: Financial Interests, Personal, Other, BMS employee: BMS; Financial Interests, Personal, Full or part-time Employment, Flavia Ejzykowicz reports being employed by and owning stock in Bristol Myers Squibb: BMS; Financial Interests, Personal, Stocks/Shares: BMS; Financial Interests, Personal, Other, Flavia Ejzykowicz reports being employed by and owning stock in Bristol Myers Squibb: BMS; Non-Financial Interests, Other, reports being employed by and owning stock in Bristol Myers Squibb: BMS; Non-Financial Interests, Personal, Other, Flavia Ejzykowicz reports being employed by and owning stock in Bristol Myers Squibb: BMS. M. Kurt: Financial Interests, Personal, Full or part-time Employment, Employee of Bristol Myers Squibb since June-2018: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares, Owns restricted shares of Bristol Myers Squibb since 2019: Bristol Myers Squibb; Non-Financial Interests, Project Lead: Bristol Myers Squibb.