3598 - Three-Year Follow-Up From the Phase 3 KEYNOTE-045 Trial: Pembrolizumab (Pembro) Versus Investigator’s Choice (Paclitaxel, Docetaxel, or Vinflunine) in Recurrent, Advanced Urothelial Cancer (UC)

Background

Based on KEYNOTE-045 (NCT02256436), pembro was approved for the treatment of locally advanced or metastatic UC that progresses during or after a platinum-containing regimen. Updated results after >3 y of follow-up since the last patient (pt) was randomized are presented.

Methods

Pts with histologically or cytologically confirmed UC, progression after platinum-containing chemo, ECOG PS 0-2, measurable disease per RECIST v1.1, or ≤ 2 lines of systemic therapy were eligible. Pts were randomly assigned 1:1 to receive pembro 200 mg Q3W or investigator’s choice of paclitaxel 175 mg/m² Q3W, docetaxel 75 mg/m² Q3W, or vinflunine 320 mg/m² Q3W. Primary end points: OS and PFS (RECIST v1.1, blinded central review). ORR and duration of response (DOR) were key secondary end points.

Results

As of Nov 30, 2018, among 542 enrolled pts (pembro, 270; chemo, 272), median (range) follow-up was 40.9 mo (36.6-48.9). Median OS was significantly longer with pembro vs chemo (10.1 vs 7.2 mo; HR, 0.72; P = 0.0003). OS rates at 24 mo were 26.9% with pembro and 14.2% with chemo. 36-mo OS rates were 20.7% and 11.0%, respectively. OS benefit with pembro vs chemo was maintained regardless of age, ECOG PS, prior therapy, liver metastases, baseline hemoglobin, time from last chemo, histology, risk factors, and chemo choice. Median PFS was similar between arms (2.1 vs 3.3 mo; HR, 0.96; P = 0.32). Median DOR for responders was longer with pembro than chemo (29.7 mo [1.6+ to 42.7+] vs 4.4 mo [1.4+ to 42.8+]), and a greater proportion of responses lasted ≥24 mo (56.8% vs 28.3%, Kaplan-Meier). Median survival follow-up for responders was 39.6 mo for pembro and 17.7 mo for chemo. ORR was higher with pembro vs chemo (21.1% vs 11.0%). Fewer patients given pembro vs chemo experienced a treatment-related adverse event of any grade (62.0% vs 90.6%) and a grade ≥3 adverse event (16.9% vs 50.2%).

Conclusions

With 3 y of follow-up, pembro continued to exhibit an OS benefit and superior safety vs chemo in pts with locally advanced or metastatic UC that progressed during or after platinum-based chemo. Pts who responded to pembro experienced a durable response with a median of > 2 y.

Clinical trial identification

NCT02256436, October 3, 2014.

Editorial acknowledgement

Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA), funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

A. Necchi: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Rainier Therapeutics; Honoraria (self), Advisory / Consultancy, Spouse / Financial dependant: Bayer; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Clovis. Y. Fradet: Advisory / Consultancy: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy: Amgen; Advisory / Consultancy: Janssen; Advisory / Consultancy, Research grant / Funding (institution): Astellas; Research grant / Funding (institution), Travel / Accommodation / Expenses: TerSera; Research grant / Funding (institution): IMV Inc. J. Bellmunt: Honoraria (self), Advisory / Consultancy: Genentech; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre-Fabre; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Honoraria (institution), Research grant / Funding (self), Research grant / Funding (institution): Takeda; Shareholder / Stockholder / Stock options: Biocline; Travel / Accommodation / Expenses: UpToDate. R. de Wit: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Research grant / Funding (institution): Bayer; Honoraria (self): Janssen; Advisory / Consultancy: Clovis. J. Lee: Honoraria (self): Novartis Korea; Honoraria (self): BMS Korea; Advisory / Consultancy: Pfizer Korea; Advisory / Consultancy: Janssen; Advisory / Consultancy: Sanofi Aventis; Advisory / Consultancy: Astellas Korea; Advisory / Consultancy: Ipsen Korea; Leadership role: Korea Cancer Study Group. L. Fong: Research grant / Funding (institution), Dr. Fong reports grants from Merck, during the conduct of the study; grants from Merck, outside the submitted work: Merck. N.J. Vozelgang: Full / Part-time employment: US Oncology; Advisory / Consultancy: Amgen, Pfizer, Bayer, Genentech/Roche, HERON, AstraZeneca, Caris Life Sciences, Fujifilm, Tolero Pharmaceuticals; Speaker Bureau / Expert testimony: Bayer, Sanofi, Genentech/Roche, Bristol-Myers Squibb, Exelixis, AstraZeneca/MedImmune; Travel / Accommodation / Expenses: Genentech/Roche, US Oncology, Pfizer, Bayer/Onyx, Exelixis, AstraZeneca/MedImmune; Shareholder / Stockholder / Stock options: Caris Life Sciences; Honoraria (self): UpToDate, Pfizer; Research grant / Funding (institution): US Oncology, Endocyte, Merck, Kintor. M.A. Climent: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Roche; Advisory / Consultancy: Pierre-Fabre. D.P. Petrylak: Advisory / Consultancy: Ada Cap (Advanced Accelerator Applications), Amgen, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Eli Lilly, Exelixis, Incyte, Janssen, Pfizer, Pharmacyclics, Roche Laboratories, Seattle Genetics, Urogen; Shareholder / Stockholder / Stock options: Bellicum, Tyme; Research grant / Funding (institution): Ada Cap (Advanced Accelerator Applications), Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Clovis, Eli Lilly, Endocyte, Genentech, Innocrin, MedImmune, Merck, Novartis, Pfizer, Progenics, Roche Laboratories, Sanofi Aventis, Seattle Genetics. T.K. Choueiri: Honoraria (self), Advisory / Consultancy: AstraZeneca, Alexion, Sanofi/Aventis, Bayer, BMS, Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Genentech, Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, Prometheus Labs, Corvus, Ipsen, Up-to-Date, NCCN, Analysis Group, NCCN, Michael J.; Advisory / Consultancy: AstraZeneca, Alexion, Sanofi/Aventis, Bayer, BMS, Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Genentech, Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, Prometheus Labs, Corvus, Ipsen, Up-to-Date, NCCN, Analysis Group.; Research grant / Funding (self), Research grant / Funding (institution): AstraZeneca, Bayer, BMS, Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Ipsen, Tracon, Genentech, Roche, Roche Products Limited, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, Prometheus Labs, Corvus, Calithera, Analysis Group, Takeda; Speaker Bureau / Expert testimony, Leadership role: NCI GU Steering Committee (unpaid), Past Chairman of Medical and Scientific Steering Committee at the Kidney Cancer Association (unpaid). W.R. Gerritsen: Advisory / Consultancy: Bristol-Myers Squibb, Amgen, Merck Sharp & Dohme, Aglaia BioMedical Ventures, Astellas Pharma, Bayer, Janssen-Cilag; Research grant / Funding (institution): Astellas Pharma, Bayer, Janssen-Cilag; Travel / Accommodation / Expenses: Amgen, Bayer. H. Gurney: Advisory / Consultancy: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy: Ipsen; Advisory / Consultancy: MSD. D.I. Quinn: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (self), Advisory / Consultancy: Exelixis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Genentech; Honoraria (self), Advisory / Consultancy: Roche; Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Astellas. S. Culine: Advisory / Consultancy: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas; Research grant / Funding (institution): Pfizer; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: MSD. C.N. Sternberg: Honoraria (self): Lilly; Advisory / Consultancy: Merck; Advisory / Consultancy: Clovis; Advisory / Consultancy: BMS; Advisory / Consultancy: Incyte; Advisory / Consultancy: AstraZeneca; Research grant / Funding (institution): Janssen. K. Nam: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. T.L. Frenkl: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. J.L. Godwin: Full / Part-time employment: Merck & Co., Inc. D.F. Bajorin: Advisory / Consultancy, Research grant / Funding (institution), Membership on an advisory board or board of directors: Merck; Advisory / Consultancy, Membership on an advisory board or board of directors: Genentech; Advisory / Consultancy, Membership on an advisory board or board of directors: Bristol-Myers Squibb; Advisory / Consultancy, Membership on an advisory board or board of directors: Urogen; Advisory / Consultancy, Research grant / Funding (institution), Membership on an advisory board or board of directors: Novartis. D.J. Vaughn: Advisory / Consultancy, Research grant / Funding (institution): Merck; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Astellas.