Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of >2 years of follow-up

被引：346

作者：

Fradet, Y. ^{[1
]}

Bellmunt, J. ^{[2
,3
]}

Vaughn, D. J. ^{[4
]}

Lee, J. L. ^{[5
,6
]}

Fong, L. ^{[7
]}

Vogelzang, N. J. ^{[8
]}

Climent, M. A. ^{[9
]}

Petrylak, D. P. ^{[10
]}

Choueiri, T. K. ^{[11
]}

Necchi, A. ^{[12
]}

Gerritsen, W. ^{[13
]}

Gurney, H. ^{[14
,15
]}

Quinn, D., I ^{[16
]}

Culine, S. ^{[17
]}

Sternberg, C. N. ^{[18
]}

Nam, K. ^{[19
]}

Frenkl, T. L. ^{[19
]}

Perini, R. F. ^{[19
]}

de Wit, R. ^{[20
]}

Bajorin, D. F. ^{[21
]}

机构：

[1] Univ Laval, Dept Surg Urol, CHU Quebec, 10 McMahon St, Quebec City, PQ G1L 3L5, Canada

[2] PSMAR IMIM Res Inst, Dept Med Oncol, Barcelona, Spain

[3] Harvard Med Sch Univ, Boston, MA USA

[4] Perelman Ctr Adv Med, Abramson Canc Ctr, Dept Med Oncol, Philadelphia, PA USA

[5] Asan Med Ctr, Dept Oncol, Seoul, South Korea

[6] Univ Ulsan, Coll Med, Seoul, South Korea

[7] Univ Calif San Francisco, Dept Med & Urol, San Francisco, CA 94143 USA

[8] Comprehens Canc Ctr Nevada, Dept Med Oncol, Las Vegas, NV USA

[9] Fdn Inst Valenciano Oncol, Dept Med Oncol, Valencia, Spain

[10] Yale Univ, Div Med Oncol, Smilow Canc Hosp, New Haven, CT USA

[11] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[12] Fdn IRCCS, Ist Nazl Tumori, Dept Med Oncol, Milan, Italy

[13] Radboud Univ Nijmegen, Dept Med Oncol, Med Ctr, Nijmegen, Netherlands

[14] Westmead Hosp, Dept Med Oncol, Sydney, NSW, Australia

[15] Macquarie Univ, Sydney, NSW, Australia

[16] Univ Southern Calif, Dept Med Oncol, Norris Comprehens Canc Ctr, Los Angeles, CA USA

[17] Hop St Louis, Dept Med Oncol, Paris, France

[18] Weill Cornell Med, Englander Inst Precis Med, Dept Med Oncol, New York, NY USA

[19] Merck & Co Inc, Dept Med Oncol, Kenilworth, NJ USA

[20] Erasmus MC, Canc Inst, Dept Med Oncol, Rotterdam, Netherlands

[21] Mem Sloan Kettering Canc Ctr, Dept Med Oncol, 1275 York Ave, New York, NY 10021 USA

来源：

ANNALS OF ONCOLOGY | 2019年 / 30卷 / 06期

关键词：

PD-L1; PD-1; pembrolizumab; urothelial cancer; OPEN-LABEL; MULTICENTER; CARCINOMA; THERAPY; CHEMOTHERAPY; NIVOLUMAB; SAFETY;

D O I：

10.1093/annonc/mdz127

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background Novel second-line treatments are needed for patients with advanced urothelial cancer (UC). Interim analysis of the phase III KEYNOTE-045 study showed a superior overall survival (OS) benefit of pembrolizumab, a programmed death 1 inhibitor, versus chemotherapy in patients with advanced UC that progressed on platinum-based chemotherapy. Here we report the long-term safety and efficacy outcomes of KEYNOTE-045. Patients and methods Adult patients with histologically/cytologically confirmed UC whose disease progressed after first-line, platinum-containing chemotherapy were enrolled. Patients were randomly assigned 1:1 to receive pembrolizumab [200mg every 3weeks (Q3W)] or investigator's choice of paclitaxel (175mg/m(2) Q3W), docetaxel (75mg/m(2) Q3W), or vinflunine (320mg/m(2) Q3W). Primary end points were OS and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central radiology review (BICR). A key secondary end point was objective response rate per RECIST v1.1 by BICR. Results A total of 542 patients were enrolled (pembrolizumab, n=270; chemotherapy, n=272). Median follow-up as of 26 October 2017 was 27.7months. Median 1- and 2-year OS rates were higher with pembrolizumab (44.2% and 26.9%, respectively) than chemotherapy (29.8% and 14.3%, respectively). PFS rates did not differ between treatment arms; however, 1- and 2-year PFS rates were higher with pembrolizumab. The objective response rate was also higher with pembrolizumab (21.1% versus 11.0%). Median duration of response to pembrolizumab was not reached (range 1.6+ to 30.0+ months) versus chemotherapy (4.4months; range 1.4+ to 29.9+ months). Pembrolizumab had lower rates of any grade (62.0% versus 90.6%) and grade >= 3 (16.5% versus 50.2%) treatment-related adverse events than chemotherapy. Conclusions Long-term results (>2 years' follow-up) were consistent with those of previously reported analyses, demonstrating continued clinical benefit of pembrolizumab over chemotherapy for efficacy and safety for treatment of locally advanced/metastatic, platinum-refractory UC. Trial registration ClinicalTrials.gov: NCT02256436.

引用

页码：970 / 976

页数：7

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Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of &gt;2 years of follow-up

Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of >2 years of follow-up