Abstract 711P
Background
N+I was superior v S in intermediate/poor-risk (IP) and intention-to-treat (ITT) pts with aRCC in CheckMate 214. We report survival, response per independent radiology review committee (IRRC), and safety after 4 years min follow-up, and an exploratory post hoc analysis in a subgroup of pts with target kidney lesion(s) without (w/o) prior nephrectomy.
Methods
Pts with clear cell aRCC were randomized 1:1 to N 3 mg/kg + I 1 mg/kg Q3W×4 then N 3 mg/kg Q2W v S 50 mg daily for 4 wks on, 2 wks off. Endpoints: overall survival (OS), objective response rate (ORR), and progression-free survival (PFS) per IRRC using RECIST v1.1 in IP (primary), ITT (secondary), and favorable (FAV; exploratory) pts.
Results
Superior OS with N+I v S was maintained in IP (HR 0.65) and ITT pts (HR 0.69); the difference in OS remained inconclusive in FAV pts (HR 0.93; Table). ORR was higher, with more ongoing responses with N+I v S in IP (65% v 50%) and ITT (65% v 52%) pts. In FAV pts, ORR was lower with N+I v S, yet more responses were ongoing (65% v 56%). Complete response (CR) rate was higher with N+I v S regardless of IMDC risk group (Table). PFS was consistent with previous reports. Incidence of any-grade and grade ≥3 treatment-related AEs remained largely unchanged with extended follow-up. In the exploratory subgroup w/o nephrectomy and with a target kidney lesion, the OS HR (0.63) was consistent with I/P and ITT pts; ORR was higher with N+I v S (34% v 15%) with no CRs in either arm, and PFS HR was 0.99 (Table; n = 53 v 55). A reduction in target kidney lesion(s) of ≥30% occurred in 35% v 20% (N+I v S) of pts. Table: 711P
| IP | ITT | FAV | w/o nephrectomy | |||||
| Arm; n | N+I; 425 | S; 422 | N+I; 550 | S; 546 | N+I; 125 | S; 124 | N+I; 53 | S; 55 |
| OS HR (95% CI) | 0.65 (0.54–0.78) | 0.69 (0.59–0.81) | 0.93 (0.62–1.40) | 0.63 (0.40–1.00) | ||||
| mOS, mo (95% CI) | 48.1 (35.6–NE) | 26.6 (22.1–33.5) | NR (46.7–NE) | 38.4 (32.0–45.0) | NR | NR (56.0–NE) | 26.1 (13.9–35.4) | 14.3 (9.7–22.6) |
| ORR per IRRC, % (95% CI) | 42 (37–47) | 27 (23–31) | 39 (35–43) | 32 (29–37) | 30 (22–38) | 52 (43–61) | 34 (22–48) | 15 (7–27) |
| CR per IRRC, % | 10 | 1 | 11 | 3 | 12 | 6 | 0 | 0 |
| PFS per IRRC, HR (95% CI) | 0.74 (0.62–0.88) | 0.89 (0.76–1.05) | 1.84 (1.29–2.62) | 0.99 (0.59–1.67) | ||||
| mPFS, mo (95% CI) | 11.2 (8.4–16.1) | 8.3 (7.0–10.8) | 12.2 (9.7–16.5) | 12.3 (9.8–15.2) | 12.4 (9.7–18.0) | 28.9 (22.1–38.4) | 8.1 (5.5–20.9) | 11.9 (8.4–17.6) |
NE, not estimable; NR, not reached
Conclusions
After 4 years min follow-up, OS and ORR benefits were maintained with N+I v S in IP and ITT pts. Responses with N+I were durable, and no new safety signals emerged. Pts w/o prior nephrectomy had shrinkage of target kidney lesions with N+I, and the OS benefit in this subgroup was consistent with the overall study population.
Clinical trial identification
NCT02231749.
Editorial acknowledgement
Professional medical writing assistance was provided by Rachel Lieberman, 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
L. Albiges: Advisory/Consultancy, To institution: Pfizer; Advisory/Consultancy, To institution: Bristol Myer Squibb; Advisory/Consultancy, to institution: Ipsen; Advisory/Consultancy, to institution: Roche; Advisory/Consultancy, to institution: MSD; Advisory/Consultancy, to institution: AstraZeneca; Advisory/Consultancy, to institution: Merck. N. Tannir: Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Bristol-Myers-Squibb; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Calithera Biosciences; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Nektar Therapeutics; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Exelixis; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Novartis; Research grant/Funding (self): Ar Pharmaceuticals; Research grant/Funding (self): Mirati Therapeutics; Research grant/Funding (self): Takeda; Research grant/Funding (self): Epizyme; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Eisai Medical Research; Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy, Travel/Accommodation/Expenses: Lilly Oncology; Advisory/Consultancy, Travel/Accommodation/Expenses: Neoleukin Therapeutics; Advisory/Consultancy, Travel/Accommodation/Expenses: Surface Oncology; Advisory/Consultancy, Travel/Accommodation/Expenses: Ono Pharmaceutical; Advisory/Consultancy, Travel/Accommodation/Expenses: Oncorena. D.F. McDermott: Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy: exelixis ; Advisory/Consultancy: Novartis; Advisory/Consultancy: X4 Pharma; Advisory/Consultancy: Array BioPharma; Advisory/Consultancy: Peloton Therapeutics; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Jounce Therapeutics; Advisory/Consultancy: alkermes; Advisory/Consultancy: Lilly; Research grant/Funding (institution): Prometheus Laboratories; Non-remunerated activity/ies: Beth Israel Deaconess Medical Center; Advisory/Consultancy, Research grant/Funding (institution): Merck. E.R. Plimack: Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Exelixis; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy: Incyte; Advisory/Consultancy: Janssen; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy: Flatiron Health; Advisory/Consultancy: Seattle Genetics; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Peloton Therapeutics; Research grant/Funding (institution): Astellas Pharma. P. Barthélémy: Advisory/Consultancy: Bristol-Myers Squib; Advisory/Consultancy: Pfizer; Advisory/Consultancy: MSD Oncology; Advisory/Consultancy: Novartis; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Roche; Advisory/Consultancy: Janssen-Cilag; Travel/Accommodation/Expenses: Amgen; Honoraria (self): Astellas Pharma. C.G. Porta: Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Ipsen; Advisory/Consultancy, Speaker Bureau/Expert testimony: EUSA; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai; Advisory/Consultancy, Speaker Bureau/Expert testimony: General Electric; Speaker Bureau/Expert testimony: Janssen; Speaker Bureau/Expert testimony: AstraZeneca; Travel/Accommodation/Expenses: Roche. T.B. Powles: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Exelixis; Honoraria (self), Advisory/Consultancy: Incyte; Honoraria (self), Advisory/Consultancy: Ipsen; Honoraria (self), Advisory/Consultancy: Merck/MSD; Honoraria (institution), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Seattle Genetics ; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Roche. F. Donskov: Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Ipsen. S. George: Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): BMS; Research grant/Funding (institution): Novartis; Advisory/Consultancy: Exelixis; Advisory/Consultancy, Research grant/Funding (institution): Corvus; Advisory/Consultancy: Genentech; Advisory/Consultancy: Sanofi/ Genzyme; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Acceleron; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Agensys; Research grant/Funding (institution): Eisai; Advisory/Consultancy: EMD Serono. C. Kollmannsberger: Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Ipsen; Advisory/Consultancy: Roche; Advisory/Consultancy: AstraZeneca. H. Gurney: Advisory/Consultancy: Pfizer; Advisory/Consultancy: Astellas; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Roche; Advisory/Consultancy: BMS. M-O. Grimm: Advisory/Consultancy, Lectures: AstraZeneca; Advisory/Consultancy, Lectures: MSD; Advisory/Consultancy: Janssen Cilag; Advisory/Consultancy, Lectures: Ono Pharma; Advisory/Consultancy, Lectures: Ipsen Pharma; Advisory/Consultancy, Lectures: Medac; Advisory/Consultancy, Lectures: Merck Serono; Advisory/Consultancy, Research grant/Funding (institution), Lectures: Novartis; Advisory/Consultancy, Research grant/Funding (institution), lectures: BMS; Advisory/Consultancy, Lectures: Pfizer; Advisory/Consultancy: Bayer HealthCare; Advisory/Consultancy, Lectures: Astellas; Advisory/Consultancy, Research grant/Funding (institution), Lectures: Intuitive Surgical; Advisory/Consultancy, Lectures: Hexal; Advisory/Consultancy, Lectures: Apogepha. Y. Tomita: Research grant/Funding (institution): Ono; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Personal fees: Bristol-Myers Squibb; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Chugai. D. Castellano Gauna: Advisory/Consultancy, Research grant/Funding (institution): Janssen Oncology; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche/Genentech; Advisory/Consultancy: Astellas Pharma; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Novartis; Advisory/Consultancy: Ipsen; Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy: MSD Oncology; Advisory/Consultancy: Bayer; Advisory/Consultancy: Lilly; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Boehringer Ingelheim. B.I. Rini: Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): GNE/Roche; Advisory/Consultancy, Research grant/Funding (institution): Aveo; Research grant/Funding (institution): Astra-Zeneca; Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy: Novartis; Advisory/Consultancy: Synthorx; Advisory/Consultancy: Peloton; Advisory/Consultancy: Compugen; Advisory/Consultancy: Arravive; Advisory/Consultancy: Surface Oncology; Advisory/Consultancy: 3D Medicines. T.K. Choueiri: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, manuscript preparation, clinical trials grants: BMS; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, manuscript preparation, clinical trials grants: Exelixis; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, manuscript preparation, clinical trials grants: Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, manuscript preparation, clinical trial grants: Merck; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, manuscript preparation, clinical trial grants: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, manuscript preparation, clinical trials grants: Lilly; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, manuscript preparation clinical trials grants: Eisai; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, manuscript preparation, clinical trials grants: Novartis; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, manjuscript preparation, clinical trials grants: GSK; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, manuscript preparation, clinical trials grants: EMD Serono; Shareholder/Stockholder/Stock options: Pionyr; Shareholder/Stockholder/Stock options: Tempest. S.S. Saggi: Shareholder/Stockholder/Stock options, Full/Part-time employment: BMS. M.B. McHenry: Shareholder/Stockholder/Stock options, Full/Part-time employment: BMS. R.J. Motzer: Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Eisai; Advisory/Consultancy, Research grant/Funding (institution): Exelixis; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy: Merck ; Advisory/Consultancy: Novartis; Advisory/Consultancy: Lilly; Advisory/Consultancy: Incyte. All other authors have declared no conflicts of interest.