Abstract 713P
Background
Conventional measures may not fully characterize the impact of immuno-oncology (I-O) agents. Previous analyses, including of CheckMate 214 data (minimum follow-up, 30 mo), have shown that patients (pts) discontinuing I-O regimens may experience periods of disease control without subsequent anticancer therapy but may still experience toxicity. Treatment-free survival (TFS) with and without toxicity can simultaneously characterize disease control and toxicity for this off-treatment period. We report updated analysis of TFS in CheckMate 214 after 42 mo minimum follow-up.
Methods
Data were analyzed from all 1096 pts from the randomized phase 3 CheckMate 214 trial of nivolumab plus ipilimumab (NIVO+IPI; N = 550) vs sunitinib (SUN; N = 546) for treatment-naïve, predominantly clear cell aRCC. TFS was defined as the area between Kaplan–Meier curves for 2 conventional time-to-event endpoints defined from randomization: time to protocol therapy cessation and time to subsequent systemic therapy or death. TFS was subdivided as TFS with and without toxicity by counting number of days with ≥1 grade ≥3 treatment-related adverse events reported. Area under each curve was estimated by the 42-mo restricted mean time to event.
Results
At 42 mo, 56% of NIVO+IPI and 47% of SUN pts were alive, 13% of NIVO+IPI and 7% of SUN pts remained on original therapy, and 31% of NIVO+IPI and 12% of SUN pts were surviving free of subsequent therapy. The 42-mo restricted mean TFS was 7.8 mo for NIVO+IPI vs 3.3 mo for SUN (7.1 vs 3.0 mo TFS without toxicity, respectively). Mean TFS was more than twice as long after NIVO+IPI than SUN for IMDC intermediate/poor-risk pts (6.9 vs 3.1 mo respectively) and 3 times as long for favorable-risk pts (11.0 vs 3.7 respectively; Table).
Conclusions
NIVO+IPI provides longer survival vs SUN. Regardless of IMDC risk group, pts on NIVO+IPI spent greater survival time treatment-free without toxicity compared with SUN. Table: 713P
| IMDC risk group | Intention to treat | Favorable | Intermediate/poor | ||||||
| 42-mo mean time to event | NIVO+IPI N=550 | SUN N=546 | Diff | NIVO+IPI N=125 | SUN N=124 | Diff | NIVO+IPI N=425 | SUN N=422 | Diff |
| Overall survival, mo | 31.5 | 28.6 | 36.2 | 37.5 | 30.1 | 25.9 | |||
| Time on protocol therapy, mo | 14.1 | 12.9 | 14.0 | 20.2 | 14.1 | 10.8 | |||
| Therapy with toxicity | 0.8 | 1.7 | 0.9 | 2.8 | 1.0 | 1.4 | |||
| Therapy without toxicity | 13.2 | 11.2 | 13.1 | 17.4 | 13.2 | 9.4 | |||
| TFS, mo (95% CI) | 7.8 | 3.3 | 4.6 (3.4–5.7) | 11.0 | 3.7 | 7.3 (4.5–10.1) | 6.9 | 3.1 | 3.7 (2.5–5.0) |
| TFS with toxicity | 0.7 | 0.3 | 0.4 (0.1–0.8) | 0.9 | 0.3 | 0.7 (–0.1 to 1.5) | 0.6 | 0.3 | 0.4 (0.0–0.7) |
| TFS without toxicity | 7.1 | 3.0 | 4.1 (3.0–5.2) | 10.1 | 3.4 | 6.6 (3.9–9.4) | 6.3 | 2.9 | 3.4 (2.2–4.5) |
| Survival after subsequent therapy initiation, mo | 9.5 | 12.4 | 11.2 | 13.6 | 9.0 | 12.0 |
Clinical trial identification
NCT02231749.
Editorial acknowledgement
Professional medical writing and editorial assistance were provided by Nicolette Belletier, PhD, of Parexel, funded by Bristol-Myers Squibb Company.
Legal entity responsible for the study
Bristol-Myers Squibb Company.
Funding
Bristol-Myers Squibb Company.
Disclosure
M. Regan: Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol Myers Squibb; Advisory/Consultancy: Tolmar Pharmaceuticals; Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Ipsen; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pierre Fabre; Research grant/Funding (self): AstraZeneca; Research grant/Funding (institution): Roche; Research grant/Funding (institution): TerSera; Research grant/Funding (institution): Bayer. T. Powles: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Bristol Myers Squibb; Honoraria (self), Advisory/Consultancy: Exelixis; Honoraria (self), Advisory/Consultancy: Incyte; Honoraria (self), Advisory/Consultancy: Ipsen; Honoraria (self), Advisory/Consultancy: Merck/MSD; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Seattle Genetics; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Roche. S. Huo: Full/Part-time employment: Bristol Myers Squibb. V. Del Tejo: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol Myers Squibb. B. Stwalley: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol Myers Squibb. M.B. Atkins: Advisory/Consultancy: Bristol Myers Squibb; Advisory/Consultancy: Merck; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Galactone; Advisory/Consultancy: Werewolf; Advisory/Consultancy: Fathom; Advisory/Consultancy: Pneuma; Advisory/Consultancy: Genentech-Roche; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Eisai; Advisory/Consultancy: Aveo; Advisory/Consultancy: Array; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Ideera; Advisory/Consultancy: Aduro; Advisory/Consultancy: ImmunoCore; Advisory/Consultancy: Boehringer-Ingelheim; Advisory/Consultancy: Iovanc; Advisory/Consultancy: Newlink Pharma; Advisory/Consultancy: Surface; Advisory/Consultancy: Alexion; Advisory/Consultancy: Acceleron; Advisory/Consultancy: Cota; Advisory/Consultancy: Pyxis Oncology; Advisory/Consultancy: Leads; Advisory/Consultancy: Amgen. D.F. McDermott: Advisory/Consultancy, Research grant/Funding (institution): Bristol Myers Squibb; 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, Research grant/Funding (institution): Peloton Therapeutics; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Jounce Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Alkermes; Advisory/Consultancy: Lilly; Research grant/Funding (institution): Prometheus Laboratories; Advisory/Consultancy: Array Biopharma. All other authors have declared no conflicts of interest.