Pembrolizumab (pembro) versus investigator’s choice of paclitaxel, docetaxel, or vinflunine in recurrent, advanced urothelial cancer (UC): 5-year follow-up from the phase 3 KEYNOTE-045 trial.
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- Joaquim Bellmunt
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA;
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- Andrea Necchi
- Vita-Salute San Rafaele University and IRCCS San Raffaele Hospital, Milan, Italy;
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- Ronald De Wit
- Erasmus MC Cancer Institute, Rotterdam, Netherlands;
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- Jae-Lyun Lee
- Asan Medical Center and University of Ulsan College of Medicine, Seoul, South Korea;
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- Lawrence Fong
- University of California San Francisco, San Francisco, CA;
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- Nicholas J. Vogelzang
- Comprehensive Cancer Centers of Nevada, Las Vegas, NV;
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- Miguel A. Climent Durán
- Fundación Instituto Valenciano de Oncología, Valencia, Spain;
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- Daniel P. Petrylak
- Smilow Cancer Hospital, Yale New Haven Health, New Haven, CT;
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- Toni K. Choueiri
- Dana-Farber Cancer Institute, Boston, MA;
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- Winald R. Gerritsen
- Radboud University Medical Center, Nijmegen, Netherlands;
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- Howard Gurney
- Westmead Hospital and Macquarie University, Sydney, NSW, Australia;
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- David I. Quinn
- USC Norris Comprehensive Cancer Center, Keck Medicine of USC, Los Angeles, CA;
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- Stephane Culine
- Hôpital Saint-Louis, Paris, France;
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- Cora N. Sternberg
- Weill Cornell Medicine, New York, NY;
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- Jin Zhi Xu
- Merck & Co., Inc., Kenilworth, NJ;
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- Blanca Homet Moreno
- Merck & Co., Inc., Kenilworth, NJ;
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- James Luke Godwin
- Merck & Co., Inc., Kenilworth, NJ;
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- Dean F. Bajorin
- Memorial Sloan Kettering Cancer Center, New York, NY;
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- David J. Vaughn
- Abramson Cancer Center, Penn Medicine, Philadelphia, PA;
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- Yves Fradet
- CHU de Québec-Université Laval, Québec City, QC, Canada;
抄録
<jats:p> 4532 </jats:p><jats:p> Background: Pembro was approved for the treatment of locally advanced or metastatic UC that progressed during or after a platinum-containing regimen, based on the phase 3 KEYNOTE-045 (NCT02256436) trial that showed significantly improved OS with use of pembro. Updated results are presented from KEYNOTE-045 after >5 y of follow-up since the last patient (pt) was randomized. Methods: KEYNOTE-045 is a randomized, multisite, open-label, phase 3 trial. Pts with histologically or cytologically confirmed UC, progression after platinum-containing chemo, ECOG PS 0-2, measurable disease per RECIST v1.1, and ≤2 prior 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/m<jats:sup>2</jats:sup> Q3W, docetaxel 75 mg/m<jats:sup>2</jats:sup> Q3W, or vinflunine 320 mg/m<jats:sup>2</jats:sup> Q3W. Primary end points are PFS (RECIST v1.1, blinded central review) and OS. ORR and duration of response (DOR) were key secondary end points. Results: As of Oct 1, 2020, among 542 enrolled pts, median time from randomization to data cutoff was 62.9 mo (range 58.6-70.9). 9.4% and 0% of pts in the pembro and chemo arms, respectively, completed 2 years of therapy. Median OS was longer for pembro vs chemo (10.1 vs 7.2 mo; HR, 0.71 [95% CI, 0.59-0.86]) overall and in pts with CPS ≥10 (8.0 vs 4.9 mo; HR, 0.59 [95% CI, 0.40-0.86]). For pts with CR or PR, median OS was not reached and 16.4 (95% CI, 11.3-25.1) mo in the pembro and chemo arms, respectively (Table). OS rates at 48 mo were 16.7% for pembro and 10.1% for chemo; 60-mo OS rates were 14.9% and 8.7%, respectively. OS benefit with pembro vs chemo continued regardless of age, ECOG PS, prior therapy, liver metastases, baseline hemoglobin, time from last chemo, histology, risk factors, and chemo choice. Median DOR for responders was longer for pembro vs chemo (29.7 mo [1.6+ to 60.5+] vs 4.4 mo [1.4+ to 63.1+]), and a greater proportion of responses lasted ≥48 mo (40.9% vs 28.3%, Kaplan-Meier) and ≥60 mo (32.8% vs 28.3%). ORR was higher for pembro vs chemo (21.9% vs 11.0%; difference 10.8% [95% CI, 4.6-17.0]). Fewer pts given pembro vs chemo experienced a treatment-related AE of any grade (62.0% vs 90.6%) or grade ≥3 (16.9% vs 50.2%). Conclusions: After 5 y, pembro maintained clinically meaningful OS benefit 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 (median >2 y). Clinical trial information: NCT02256436 .[Table: see text] </jats:p>
収録刊行物
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- Journal of Clinical Oncology
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Journal of Clinical Oncology 39 (15_suppl), 4532-4532, 2021-05-20
American Society of Clinical Oncology (ASCO)