971P - Treatment-free survival, with and without toxicity, as a novel outcome applied to immuno-oncology agents in advanced renal cell carcinoma

Abstract

BackgroundConventional measures such as median progression-free survival may suboptimally characterize the full impact of immuno-oncology (I-O) agents vs other systemic anticancer therapies. Patients discontinuing I-O agents may experience periods of disease control without needing subsequent systemic anticancer therapy (Rx) but may still experience toxicity (TOX). Treatment-free survival (TFS) ± TOX can simultaneously characterize disease control and TOX for this off-treatment period. MethodsData were analyzed from all 1082 patients initiating Rx on the randomized phase 3 CheckMate 214 trial of nivolumab + ipilimumab (NIVO+IPI) vs sunitinib (SUN) for treatment-naïve predominantly clear cell advanced renal cell carcinoma. TFS is defined as the area between Kaplan–Meier (KM) curves for 2 conventional time-to-event endpoints defined from randomization: time to protocol Rx cessation and time to subsequent Rx or death. TFS was subdivided as TFS with and without TOX by defining a third endpoint: time to cessation of Rx and TOX. TOX was defined as grade ≥3 Rx-related adverse events. Area under each KM curve was estimated by the 36-month restricted mean time to event. ResultsAt 36 months, 60% of NIVO+IPI and 51% of SUN patients were alive, 15% NIVO+IPI and 9% SUN remained on original Rx, and 34% NIVO+IPI and 19% SUN patients were surviving free of subsequent Rx. The 36-month restricted mean TFS was 6.7 and 2.9 months for all NIVO+IPI and SUN patients, respectively (6.4 vs 2.8 months TFS without TOX). The table shows time by TFS subdivision and IMDC risk.Table971PTableIMDC risk groupAllFavorableIntermediate/PoorN=547N=535N=124N=119N=423N=416Restricted mean timeNIVO+IPISUNDifferenceNIVO+IPISUNDifferenceNIVO+IPISUNDifferenceOS, months28.025.632.032.926.923.5Time on protocol Rx, months13.412.713.520.113.410.6TFS, months (95% CI)6.72.93.8 (2.4–5.3)9.82.77.2 (4.4–10.0)5.83.02.8 (1.7–4.0)TFS with TOX0.40.10.2 (0.05–0.4)0.50.10.4 (0.2–0.6)0.30.2–0.1 (–0.03–0.3)TFS without TOX6.42.83.6 (2.3–5.0)9.42.66.8 (4.1–9.5)5.52.82.7 (1.6–3.8)Survival after subsequent Rx initiation, months7.910.08.710.27.710.0IMDC, International Metastatic Renal Cell Carcinoma Database Consortium; OS, overall survival. ConclusionsNIVO+IPI provides longer survival and delayed time to subsequent Rx vs SUN. More importantly, NIVO+IPI provides longer TFS without TOX, during which patients do not require Rx and are free from TOX. Given the durability of I-O responses relative to SUN after Rx cessation, it will be of interest to measure TFS over time. Clinical trial identificationNCT02231749. Editorial acknowledgementNicolette Belletier, PhD, and Lawrence Hargett of Parexel. Legal entity responsible for the studyBristol-Myers Squibb. FundingBristol-Myers Squibb and ONO Pharmaceutical Company Limited. DisclosureM.M. Regan: Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): IPSEN; Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Research grant / Funding (institution): Veridex; Research grant / Funding (institution): OncoGenex; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Ferring; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Pierre Fabre; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Millennium Pharmaceuticals; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Sotio; Research grant / Funding (institution): Dendreon; Research grant / Funding (institution): Medivation. M.B. Atkins: Honoraria (self), Advisory / Consultancy: BMS; Advisory / Consultancy: Genentech; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy: X4 Pharma; Advisory / Consultancy: Merck; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Acceleron; Advisory / Consultancy: Eisai; Advisory / Consultancy: Glactone Pharma; Advisory / Consultancy: Agenus; Advisory / Consultancy: Array BioPharma; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Aduro Biotech; Advisory / Consultancy: Newlink Genetics/Pharmatech; Advisory / Consultancy: Arrowhead Pharmaceuticals; Advisory / Consultancy: Werewolf Pharma; Advisory / Consultancy: Oncolys BioPharma; Advisory / Consultancy: Surface; Advisory / Consultancy: Iovance Biotherapeutics. T. Powles: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self): Merck; Honoraria (self): BMS; Honoraria (self): Pfizer; Honoraria (self): IPSEN; Honoraria (self): Novartis; Honoraria (self): Exelixis. S. Yang: Shareholder / Stockholder / Stock options, Full / Part-time employment: BMS. J.L. Johansen: Shareholder / Stockholder / Stock options, Full / Part-time employment: BMS. S. Rao: Shareholder / Stockholder / Stock options, Full / Part-time employment: BMS. K.M. Gooden: Shareholder / Stockholder / Stock options, Full / Part-time employment: BMS. D.F. McDermott: Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Exelixis; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: X4 Pharma; Advisory / Consultancy: Array Biophrama; Advisory / Consultancy, Research grant / Funding (institution): Peloton Therapeutics; Advisory / Consultancy: EMD Serono; Advisory / Consultancy: Jounce Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): Alkermes; Advisory / Consultancy: Lilly; Full / Part-time employment: BIDMC; Research grant / Funding (institution): Promethus Laboratories. All other authors have declared no conflicts of interest.