Abstract 2368
Background
Depth of response (DepOR; max % reduction from baseline in sum of target lesion diameters), has shown prognostic value for long-term survival in multiple malignancies. Among aRCC patients (pts) in CheckMate 214, objective response and complete response rates were higher and more durable, and overall survival (OS) was greater (intention-to-treat: HR 0.71, P = 0.0003; intermediate/poor-risk pts: HR 0.66, P < 0.0001), for nivolumab + ipilimumab (N+I) vs sunitinib (S) at 30-mo min follow-up. This exploratory analysis evaluated the relationship between DepOR and OS in CheckMate 214 to determine a potential DepOR threshold predictive of long-term OS with N+I.
Methods
Pts with previously untreated aRCC were randomized 1:1 to N+I (3 mg/kg + 1 mg/kg IV) Q3W for 4 doses, followed by N (3 mg/kg IV) Q2W, or S 50 mg/day orally for 4 wk (6-wk cycles). An exploratory analysis of OS by DepOR quartiles was conducted (Q0, no reduction; Q1, >0–≤25%; Q2, >25–≤50%; Q3, >50–≤75%; Q4, >75–≤100%).
Results
Of 550 and 546 pts randomized to N+I or S, 479 and 459, respectively, had postbaseline target lesion measurements. Overall, greater DepOR was associated with improved OS (Table). Pts on N+I with >50–≤75% (Q3) tumor reduction had similar OS as those with >75% (Q4) reduction, whereas only Q4 pts achieved comparable OS with S (203/550 [37%] N+I vs 46/546 [8%] S randomized pts). Receiver operating characteristic analysis supported a > 50% DepOR threshold for greatest OS benefit with N+I. Additional analyses of the relationship between DepOR and outcomes across arms will be presented.Table:
950P
DepOR | N+I N = 479 | S N = 459 | ||||
---|---|---|---|---|---|---|
n (%) | Median OS, mo (95% CI) | OS probability vs Q0, HR (95% CI) | n (%) | Median OS, mo (95% CI) | OS probability vs Q0, HR (95% CI) | |
Q0a | 105 (22) | 26.9 (18.6–NE) | – | 94 (20) | 12.4 (9.5–15.0) | – |
Q1 | 107 (22) | NR (29.9–NE) | 0.63 (0.43–0.93)b | 137 (30) | 31.9 (22.1–37.8) | 0.48 (0.35–0.67)b |
Q2 | 64 (13) | NR (26.1–NE) | 0.65 (0.42–1.01)b | 109 (24) | NR (NE) | 0.21 (0.14–0.32)b |
Q3 | 96 (20) | NR (NE) | 0.22 (0.13–0.38)b | 73 (16) | NR (NE) | 0.18 (0.11–0.29)b |
Q4 | 107 (22) | NR (NE) | 0.18 (0.11–0.32)b | 46 (10) | NR (NE) | 0.08 (0.03–0.17)b |
Among Q0 pts, median OS was longer and OS probabilities were notably higher with N+I vs S.
bP < 0.0001 when compared with Q0 in the same arm. CI, confidence interval; HR, hazard ratio; NE, not estimable; NR, not reached.
Conclusions
The relationships between DepOR and OS are distinct for N+I vs S, with a greater percentage of N+I pts having prolonged OS. Similar notable OS benefits in N+I DepOR Q3 and Q4 suggest that a DepOR threshold >50% may be a useful indicator of potential for long-term survival with N+I in aRCC pts. Prospective analyses to determine clinical applications are needed.
Clinical trial identification
NCT02231749.
Editorial acknowledgement
Jen Tyson, PhD, and Lawrence Hargett of Parexel.
Legal entity responsible for the study
Bristol-Myers Squibb.
Funding
Bristol-Myers Squibb and ONO Pharmaceutical Company Limited.
Disclosure
V. Grünwald: Research grant / Funding (institution), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Non-remunerated activity/ies: MSD; Research grant / Funding (institution), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Novartis; Research grant / Funding (institution), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: AstraZeneca; Research grant / Funding (institution), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Non-remunerated activity/ies: BMS; Travel / Accommodation / Expenses, Non-remunerated activity/ies: Merck Serono; Travel / Accommodation / Expenses, Non-remunerated activity/ies: Roche; Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Lilly; Travel / Accommodation / Expenses, Non-remunerated activity/ies: PharmaMar; Travel / Accommodation / Expenses: Nanobiotix; Travel / Accommodation / Expenses: Janssen; Travel / Accommodation / Expenses, Non-remunerated activity/ies: Eisai; Research grant / Funding (institution), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Ipsen; Research grant / Funding (institution), Travel / Accommodation / Expenses: Eusa Pharm. T.K. Choueiri: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Honoraria (self), Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Cerulean; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Eisai; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Foundation Medicine Inc; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Exelixis; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Genentech; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: GlaxoSmithKline; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Peloton; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Prometheus Labs; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Corvus; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: IPSEN; Research grant / Funding (institution): Tracon; Research grant / Funding (institution): Astellas. 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): Peloton; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Aveo; Advisory / Consultancy: Novartis; Advisory / Consultancy: Synthorx; Advisory / Consultancy: Compugen; Advisory / Consultancy: Merck; Advisory / Consultancy: Corvus; Advisory / Consultancy: Exelixis; Shareholder / Stockholder / Stock options: PTC Therapeutics. T. Powles: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Merck; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Ipsen; Research grant / Funding (institution): Exelixis. S. George: Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Research grant / Funding (institution): Novartis; Travel / Accommodation / Expenses: Exelixis; Travel / Accommodation / Expenses: Janssen; Research grant / Funding (institution), Travel / Accommodation / Expenses: Corvus; Travel / Accommodation / Expenses: Genentech; Travel / Accommodation / Expenses: Sanofi/Genzyme; Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (institution): Acceleron; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Agensys; Research grant / Funding (institution): Eisai; Travel / Accommodation / Expenses: EMD Serono. M. Grimm: Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Bayer HealthCare; Travel / Accommodation / Expenses: Astellas; Travel / Accommodation / Expenses: Intuitive Surgical; Travel / Accommodation / Expenses: Sanofi Aventis; Travel / Accommodation / Expenses: Hexal; Travel / Accommodation / Expenses: Apogepha; Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: Janssen Cilag; Travel / Accommodation / Expenses: Ono Pharma; Travel / Accommodation / Expenses: IPSEN. M.B. McHenry: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. M. Maurer: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. R.J. Motzer: Research grant / Funding (institution): BMS; 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; Travel / Accommodation / Expenses: Incyte; Advisory / Consultancy: Lilly. H.J. Hammers: Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Exelixis; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: Armo Biosciences; Advisory / Consultancy: Novartis. N.M. Tannir: Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Nektar Therapeutics; Advisory / Consultancy: Oncorena; Advisory / Consultancy, Research grant / Funding (institution): Exelixis; Advisory / Consultancy: Eisai; Research grant / Funding (institution): Calithera Bioscience; Advisory / Consultancy: Ono Pharmaceutical. L. Albiges: Advisory / Consultancy: BMS; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Ipsen; Advisory / Consultancy: MSD; Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca.
Resources from the same session
4596 - A Phase 2, Open-Label, Randomized, Multicenter Trial of Encorafenib + Binimetinib Evaluating a Standard-dose and a High-dose Regimen in Patients With BRAFV600-Mutant Melanoma Brain Metastasis (MBM) (POLARIS)
Presenter: Michael Davies
Session: Poster Display session 3
Resources:
Abstract
1891 - Continuation of annual screening mammograms and breast-cancer mortality in women over 70
Presenter: Xabier Garcia De Albeniz
Session: Poster Display session 3
Resources:
Abstract
5587 - Introducing standardized medical procedure and dynamic decision support program in precision oncology for the community of practice
Presenter: Istvan Petak
Session: Poster Display session 3
Resources:
Abstract
4757 - Effectively using primary care givers in oncology care through capacity building, task sharing and techno-mentoring.
Presenter: Dinesh Pendharkar
Session: Poster Display session 3
Resources:
Abstract
4497 - A single institution review of capecitabine related acute admissions and cost analysis
Presenter: Gemma Dart
Session: Poster Display session 3
Resources:
Abstract
2187 - Health status of middle-aged and older cancer survivors in China: results from the China Health and Retirement Longitudinal Study (CHARLS)
Presenter: Jiarui Li
Session: Poster Display session 3
Resources:
Abstract
5101 - Crossed looks on lung cancer perception and knowledge from general public and physicians in France: results of a two-fold survey
Presenter: Céline Mascaux
Session: Poster Display session 3
Resources:
Abstract
4354 - Knowledge and perception of clinical trials (CTs) and attitude towards participation among Polish oncological patients - A pilot survey
Presenter: Artur Kotowski
Session: Poster Display session 3
Resources:
Abstract
3499 - Achieving best possible cancer treatment outcomes in care pathways through benchmarking; ABC-Benchmarking
Presenter: Anke Wind
Session: Poster Display session 3
Resources:
Abstract
2270 - Impact of 10-day Fulbright Specialist Program (FSP) and Project Pink Blue (PPB) Education Sessions on Medical Oncology knowledge among Doctors that treat cancer in Nigeria
Presenter: Mike Martin
Session: Poster Display session 3
Resources:
Abstract