Advanced UC is most often seen in senior pts, in whom age-related complications such as renal dysfunction and poor performance status (PS) preclude ∼50% from receiving standard first-line cisplatin treatment. In the phase 2 KEYNOTE-052 trial (NCT02335424), first-line pembro had clinically meaningful antitumor activity (ORR, 24%) and was well tolerated in cisplatin-ineligible pts with UC. Results from the subgroup of pts who were considered senior (≥65 y or ≥ 75 y) and had ECOG PS 2 are presented.
Pts were cisplatin ineligible and had advanced UC, measurable disease (per RECIST v1.1), ECOG PS 0-2, and no prior systemic chemotherapy. Pts received pembro 200 mg Q3W. Radiographic imaging was performed at wk 9, then Q6W for the first year, and Q12W thereafter. The primary end point was ORR (RECIST v1.1, independent radiology review).
Of 370 pts, 302 (82%) were ≥65 y, 179 (48%) were ≥75 y, 120 (32%) were ≥65 y with ECOG PS 2, and 78 (21%) were ≥75 y with ECOG PS 2. Median follow-up was 5 mo. ORR (95% CI) was similar to that reported in the overall study population regardless of age cutoff (Table). Poor PS did not impact ORR in senior pts (Table). 6-mo PFS rates were consistent across senior groups (Table). 64% (≥65 y), 66% (≥75 y), 58% (≥65 and ECOG PS 2), and 64% (≥75 y and ECOG PS 2) of pts experienced treatment-related AEs. 16% of pts ≥65 and ≥75 y and 17% of pts ≥65 and ≥75 y with ECOG PS 2 experienced grade ≥3 treatment-related AEs.Table:
857P Efficacy Outcomes
|≥65 y n = 302||≥75 y n = 179||≥65 y and ECOG PS 2 n = 120||≥75 y and ECOG PS 2 n = 78|
|ORR, % (95% CI)||23 (19-28)||23 (17-30)||24 (17-33)||27 (18-38)|
|CR||4 (2-7)||2 (1-6)||2 (0.2-6)||3 (0.3-9)|
|PR||19 (15-24)||21 (15-27)||22 (15-31)||24 (15-35)|
|6-mo PFS, %||30%||27%||28%||27%|
Results from subgroup analyses of senior pts with poor PS in KEYNOTE-052 confirm that first-line pembro elicits clinically meaningful responses consistent with the overall study population. Pembro is well tolerated in cisplatin-ineligible pts with UC, including those who are senior with poor PS.
Clinical trial identification
NCT02335424; January 7, 2015
Legal entity responsible for the study
Merck & Co., Inc.
Merck & Co., Inc.
P. Grivas: Bayer, Merck, AstraZeneca: consult & trial spnsr; Genentech: consult & unbrand progm, trial spnsr; Dendreon, Exelixis, ClovisOncol: consult; Bristol-Myers Squib: consult & unbrand prgrm; Genmab: Grant; Mirati, Oncogenex, Pfizer: to Cleve Clin Found for clin trial. E. Plimack: Ad Board: AstraZeneca, Bristol-Myers Squib, Eli Lilly and Company, Exelexis, Genentech, Horizon Pharma, Inovio, Novartis, Pfizer, Roche; Grant/Trials: Acceleron, Agensys, AstraZeneca, Bristol-Myers Squib, Merck, Peloton, Pfizer. Patent: U.S. Patent Application No.: 14/588,503, Filed 1/2/2015. A.V. Balar: Merck, Roche/Genentech: Research Support, Consulting/Advisory Role, Honoraria. AstraZeneca/Medimmune, Pfizer/EMD Serono: Consulting/Advisory Role. D. Castellano: Advisory board member: Ipsen, Roche, Pfizer; Speakers’ bureau: Pfizer, Astellas, Janssen; Honoraria: Pfizer, Novartis and Bayer. P.H. O\'Donnell: Honorarium: Genentech/Roche, Novartis, Merck, AstraZeneca, Astellas Pharma, Seattle Genetics, Inovio, Parexel. Institutional research funding: Boehringer Ingelheim, Merck, Genentech/Roche, AstraZeneca/Medimmune, Acerta Pharma, Janssen. J. Bellmunt: Merck: Educational lectures and adboards, Genentech: Lectures and adboards, Pfizer: Adboard, AstraZeneca: Lectures and adboard. T. Powles: Research funding: Merck, AstraZeneca, Roche Honoraria: Pfizer, Merck, AstraZeneca, Roche, Novartis Travel expenses, including accommodations: Pfizer, Merck, AstraZeneca, Roche, Novartis N. Hahn: Grant Res: Novartis, OncoGenex, Mirati, Merck, Genentech, Bristol-Myers Squib, Heat Biologics, Acerta, AstraZeneca, Principia Bioph, Seattle Genetics. Consult: Merck, Genentech, Inovio, Bristol-Myers Squib, AstraZeneca, Pieris Pharma, TARIS Biomedical, Champions Oncology, Health Advances. R. de Wit: Ad Board: Merck, Roche, Sanofi, Lilly. D. Bajorin: Advisory board member: Roche, Merck, Genentech, Pfizer, AstraZeneca; Research funding: Merck, Genentech, Bristol-Myers Squib, Roche, Novartis; Honoraria: Merck, Genentech Travel expenses, including accommodations: Merck, Genentech, Bristol-Myers Squib, Roche, Novartis. M.C. Ellison, T. Frenkl: Employment: Merck & Co. S.M. Keefe: Employment: Merck & Co., Inc. travel expenses, including accommodations: Merck & Co., Inc. J. Vuky: Advisory board member: Pfizer; Research funding: Pfizer, Merck, Roche, Celldex.