2368 - Association Between Depth of Response and Overall Survival: Exploratory Analysis in Patients With Previously Untreated Advanced Renal Cell Carcinoma (aRCC) in CheckMate 214

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

Among Q0 pts, median OS was longer and OS probabilities were notably higher with N+I vs S.

P < 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.