Well-defined prognostic factors (PF) and risk groups have been shown to impact OS in first- and second-line chemotherapy (chemo) for UC. Post hoc analysis of survival outcome per level of risk was conducted using data from the phase 3 KEYNOTE-045 trial (NCT02256436).
Data from the Oct 26, 2017 data cut were included. The presence or absence of 4 predefined criteria applied at study randomization was noted for each patient: ECOG PS (0 vs 1 or 2), hemoglobin level (<10 g/dL vs ≥ 10 g/dL), liver metastases (yes vs no), and time from prior chemotherapy (<3 months vs ≥ 3 months). Patients were grouped per the number of PFs they had (0, 1, 2, or 3/4), and OS was estimated for each risk group receiving pembrolizumab (pembro) or chemo, using Kaplan-Meier (K-M) statistics.
Data from 529/542 patients were included. Stratified randomization ensured that the distribution of risk levels was similar between the 2 treatment arms. Overall, OS decreased with increasing numbers of PFs for pembro (from 19 to 5 months) and chemo (from 18 to 3 months) (Table). Within the chemo arm, the results of the K-M survival profiles were consistent with previously published data, in which each risk group had different outcomes. Within the pembro arm, outcomes of pts with 0 and 1 PF were distinct from those with 2 and 3/4 PF groups. OS was longer with pembro than with chemo across all PF subgroups.Table: 901P
|0 PFS||1 PF||2 PFs||3 or 4 PFs|
|OS||Pembro n = 54||Chemo n = 45||Pembro n = 97||Chemo n = 97||Pembro n = 66||Chemo n = 80||Pembro n = 45||Chemo n = 45|
|Median (95% CI),months||18.5 (14.1-NE)||17.6 (10.2-24.2)||12.6 (8.1-18.9)||8.8 (7.4-11.2)||5.1 (2.8-8.7)||4.7 (3.5-6.1)||4.6 (2.3-7.4)||3.4 (2.4-4.6)|
|24-month OS, %||41.4||36.7||35.3||17.8||12.6||5.6||13.7||NR|
|30-month OS, %||41.4||31.6||25.9||13.7||NR||5.6||11.4||NR|
|HR for OS||0.81 (0.49-1.36)||0.67 (0.48-0.93)||0.82 (0.57-1.16)||0.61 (0.39-0.97)|
OS within the pembro and chemo arms decreased with increasing numbers of PFs. OS of patients treated with pembro was longer than those receiving chemo across the risk groups. Patients treated with pembro who had 2 or 3/4 PFs had overall similar outcomes. Additional analyses are needed to characterize novel risk models for patients treated with immunotherapies.
Clinical trial identification
NCT02256436, trial initiation date: October 3, 2014.
Legal entity responsible for the study
Merck & Co., Inc.
Merck & Co., Inc.
Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck & Co., Inc., Kenilworth, NJ, USA.
J. Bellmunt: Consultant/advisory: Pierre Fabre, Astellas, Pfizer, Merck, Genentech, Novartis, AstraZeneca, BMS; Travel: Pfizer, MSD Oncology; Research funding: Millennium, Sanofi. R. de Wit: Consultant/advisory: Sanofi, Merck, Lilly, Roche/Genentech; Honoraria: Sanofi, Lilly, Roche/Genentech, Merck; Research funding: Sanofi. D.J. Vaughn: Research funding: Merck, Roche, Genentech. Y. Fradet: Consultant/Advisory: Merck, Astellas, Roche, AstraZeneca; Research funding: Astellas; Travel: Roche. J.L. Lee: Consultant/Advisory: Astellas, AstraZeneca, Eisai; Honoraria: Pfizer, Astellas, Novartis, BMS; Research funding: Pfizer, Janssen, Novartis, Exelixis, BMS, Roche/Genentech. L. Fong: Consultant/Advisory: Atreca, Ideava Biosciences, MIODx; Research funding: BMS, Abbvie, Roche/Genentech, Janssen, Merck, Nektar. N.J. Vogelzang: Consultant/Advisory: Amgen, Pfizer, Bayer, Genentech/Roche, AstraZeneca, Caris Life Science, Tolero; Speakers’ bureau: Bayer, Sanofi, BMS, Exelixis, AstraZeneca, Stock, Caris Life Sciences, Honoraria: Pfizer; Research funding: Endocyte, Merck. M.A. Climent: Honoraria: Roche, BMC, Bayer, Astella, Sanofi, Pfizer, Novartis; Consulting/Advisory: Janssen, Pfizer, Roche, Sanofi, Astellas Pharma, Bayer; Travel: Astellas, Janssen, Pfizer. D. Petrylak: Consultant/Advisory: Bayer, Johnson & Johnson, Exelixis, Ferring, Millennium, Medivation, Pfizer, Roche, Sanofi; Research funding: Johnson & Johnson, Sanofi, Endocyte, Genentech, Merck, Astellas, Novartis, AstraZeneca, Bayer, Lilly, Seattle Genetics. T.K. Choueiri: Consultant: Pfizer, Bayer, Novartis, GlaxoSmithKline, Merck, BMS Roche/Genentech, Eisai, AstraZeneca, Exelixis, Alligent; Honoraria: NCCN; Research funding: Pfizer, Novartis, Merck, Exelixis, GlaxoSmithKline, BMS, AstraZeneca, Roche/Genentech, Celldex. W.R. Gerritsen: Consultant/Advisory: BMS, Amgen, Merck, Aglaia Biomedical Ventures, Astellas, Bayer, Janssen-Cilag; Speakers’ bureau: Astellas, Bayer, Janssen-Cilag; Travel: Amgen, Bayer. H. Gurney: Consultant/Advisory: BMS, Ipsen, Merck, AstaZeneca; Travel: Astellas, Sanofi; Honoraria: Roche, Astellas; Research funding: Pfizer. D.I. Quinn: Consultant/Advisory: Astellas, Pfizer, BMS, Genetech/Roche, Merck, Bayer, Exelixis, AstraZeneca, Sanofi; Honoraria: Bayer, Astellas, Pfizer, Genentech/Roche, Merck, BMS, AstraZeneca, Sanofi, Millennium, Genentech/Roche, GlaxoSmithKline. S. Culine: Consultant/Advisory: Roche, Janssen; Speakers bureau: Astellas, Roche, Merck; Travel: Amgen, Astellas, Janssen. C.N. Sternberg: Honararia: OncoGenex, Lilly, Janssen, Merck, BMS, AstraZeneca, Roche/Genentech; Research funding: Lilly, Janssen, Merck, BMS, AstraZeneca, Roche/Genentech. E. Jensen: Employment: Merck. T. Frenkl, R.F. Perini: Employment and stock. D. Bajorin: BMS, Novartis, Roche/Genentech, Merck, Lilly, Fidia Farmaceutici, Urogen Pharma, Lilly Pfizer, EMD Serono; Honoraria: Merck; Research funding: Dendreon, Novartis, Amgen. Genentech/Roche, Merck, BMS. All other authors have declared no conflicts of interest.