103P - Long-term survivorship rates among previously treated patients with advanced renal cell carcinoma (aRCC) achieving objective response with nivolumab

Background

Durability of response with immune checkpoint inhibitors is often associated with long-term survival benefits. This analysis explored the relationship between achieving objective response (OR) with nivolumab (NIVO) and the possibility of previously treated patients with aRCC being long-term survivors (LTS) in the phase 3 CheckMate 025 trial.

Methods

Mixture cure models (MCMs) were applied to analyze overall survival (OS) and duration of response (DoR) data with ≥7 years of follow-up separately for patients achieving confirmed OR (n=94, 22.9%) with NIVO. In both analyses, LTS were only subject to risk of non–disease-related (NDR) mortality. In the DoR analysis, LTS were also assumed to remain in response until death. OS/DoR outcomes for non-LTS were subject to both disease-related and NDR risk, and modeled by parametric distributions. NDR mortality rates were derived via publicly available World Health Organization lifetable data matched to the study population’s demographic characteristics. The fraction of LTS and OS/DoR for non-LTS were estimated simultaneously through maximum likelihood methods. Candidate MCMs were evaluated based on statistical fit criteria, visual fits to the observed OS/DoR data, and corresponding hazard trends.

Results

Across all clinically plausible candidate models, log-normal MCMs provided the best fit to the observed data for both endpoints, and estimated the fractions of LTS (95% CI) among responders as 31.5% (12.1%–60.5%) and 7% (1.1%–33.4%) from the OS and DoR data, respectively. The range of estimated fractions of LTS across all plausible models was narrower in the DoR analysis (5.7%–11.2%) than in the OS analysis (28.6%–41.1%). Projected 30-year mean OS and DoR for responders from the best-fitting MCMs were 9.35 and 3.30 years, respectively.

Conclusions

MCMs estimated the subgroup achieving OR with NIVO in the CheckMate 025 trial to have a higher fraction of LTS than those previously reported for the entire NIVO arm and a modest proportion of LTS to be in response until death. Even with long-term follow-up data, estimated fractions of LTS were subject to uncertainty due to the limited number of patients contributing to the formation of OS and DoR plateaus.

Clinical trial identification

NCT01668784.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

S. George: Financial Interests, Personal, Advisory Board, advisor/consultant: BMS, Bayer, Pfizer, Exelixis, Sanofi/Genzyme, Seattle Genetics, EMD Serono, Eisai, Merck, Aveo, QED therapeutics; Financial Interests, Personal, Advisory Board, Advisor/consultant: Novartis, AstraZeneca; Financial Interests, Institutional, Local PI: Pfizer, Merck, Agensys, Novartis, BMS, Bayer, Eisai, Seattle Genetics, Surface Oncology, Exelixis, Aravive, Aveo, Gilead. J. Larkin: Financial Interests, Personal, Invited Speaker: BMS, Pfizer, Roche, Pierre Fabre, AstraZeneca, Novartis, EUSA Pharma, MSD, Merck, GSK, Ipsen, Aptitude, Eisai, Calithera, Ultimovacs, Seagen, Goldman Sachs, eCancer, Inselgruppe, Agence Unik; Financial Interests, Personal, Other, Consultancy: Incyte, iOnctura, Apple Tree, Merck, BMS, Eisai, Debipharm; Financial Interests, Personal, Other, Honorarium: touchIME, touchEXPERTS, VJOncology, RGCP, Cambridge Healthcare Research, Royal College of Physicians; Financial Interests, Institutional, Funding: BMS, MSD, Novartis, Pfizer, Achilles, Roche, Nektar, Covance, Immunocore, Pharmacyclics, Aveo. L.M. Garcia Fernandez: Financial Interests, Institutional, Advisory Role: Parexel International. J. May, M. Dyer, M. Kurt: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks or ownership: Bristol Myers Squibb. M. Patel: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb/Medarex, LEO Pharma; Other, Personal, Other, An Immediate Family Member: Pfizer, CVS Health; Financial Interests, Personal, Stocks or ownership: Sanofi, Bristol Myers Squibb/Medarex; Financial Interests, Personal, Stocks or ownership, An Immediate Family Member: CVS Health. All other authors have declared no conflicts of interest.