Efficacy and safety of pembrolizumab in metastatic urothelial carcinoma: results from KEYNOTE-045 and KEYNOTE-052 after up to 5 years of follow-up

被引：75

作者：

Balar, A. V. ^{[1
]}

Castellano, D. E. ^{[2
]}

Grivas, P. ^{[3
]}

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

Powles, T. ^{[5
]}

Vuky, J. ^{[6
]}

Fradet, Y. ^{[7
]}

Lee, J. -L. ^{[8
]}

Fong, L. ^{[9
]}

Vogelzang, N. J. ^{[10
]}

Climent, M. A. ^{[11
]}

Necchi, A. ^{[12
,13
]}

Petrylak, D. P. ^{[14
]}

Plimack, E. R. ^{[15
]}

Xu, J. Z. ^{[16
]}

Imai, K. ^{[16
]}

Moreno, B. H. ^{[16
]}

Bellmunt, J. ^{[17
]}

de Wit, R. ^{[18
]}

O'Donnell, P. H. ^{[19
]}

机构：

[1] New York Univ Langone Hlth, Perlmutter Canc Ctr, New York, NY USA

[2] Hosp Univ 12 Octubre, Dept Med Oncol, Madrid, Spain

[3] Univ Washington, Fred Hutchinson Canc Ctr, Dept Med, Div Oncol, Seattle, WA USA

[4] Abramson Canc Ctr, Penn Med, Div Hematol Oncol, Philadelphia, PA USA

[5] Queen Mary Univ London, Dept Genitourinary Oncol, Barts Canc Inst, London, England

[6] Oregon Hlth & Sci Univ, Knight Canc Inst, Dept Med Oncol, Portland, OR USA

[7] Univ Laval, CHU Quebec, Dept Surg Urol, Quebec City, PQ, Canada

[8] Univ Ulsan, Coll Med, Dept Oncol, Asan Med Ctr, Seoul, South Korea

[9] Univ Calif San Francisco, Dept Med, San Francisco, CA USA

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

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

[12] Univ Vita Salute San Raffaele, Dept Med Oncol, Milan, Italy

[13] IRCCS San Raffaele Hosp, Milan, Italy

[14] Yale New Haven Hlth, Dept Internal Med Med Oncol, Smilow Canc Hosp, New Haven, CT USA

[15] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA USA

[16] Merck & Co Inc, Dept Med Oncol, Rahway, NJ USA

[17] Harvard Med Sch, Dana Farber Canc Inst, Dept Hematol & Oncol, Boston, MA USA

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

[19] Univ Chicago, Sect Hematol Oncol, Dept Med, Chicago, IL USA

来源：

ANNALS OF ONCOLOGY | 2023年 / 34卷 / 03期

关键词：

urothelial carcinoma; pembrolizumab; cisplatin-ineligible; cisplatin resistant; refractory; OPEN-LABEL; CHEMOTHERAPY; MULTICENTER; ATEZOLIZUMAB; IMVIGOR211; SURVIVAL;

D O I：

10.1016/j.annonc.2022.11.012

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Immune checkpoint inhibitors are a standard therapy in metastatic urothelial carcinoma (UC). Long-term follow-up is necessary to confirm durability of response and identify further safety concerns. Patients and methods: In KEYNOTE-045, patients with metastatic UC that progressed on platinum-containing chemotherapy were randomly assigned 1:1 to receive pembrolizumab or investigator's choice of paclitaxel, docetaxel, or vinflunine. Primary endpoints were progression-free survival per RECIST version 1.1 by blinded independent central review (BICR) and overall survival. In KEYNOTE-052, cisplatin-ineligible patients with metastatic UC received first-line pembrolizumab. The primary endpoint was objective response rate per RECIST version 1.1 by BICR. Results: A total of 542 patients (pembrolizumab, n = 270; chemotherapy, n = 272) were randomly assigned in KEYNOTE-045. The median follow-up was 62.9 months (range 58.6-70.9 months; data cut-off 1 October 2020). At 48 months, overall survival rates were 16.7% for pembrolizumab and 10.1% for chemotherapy; progression-free survival rates were 9.5% and 2.7%, respectively. The median duration of response (DOR) was 29.7 months (range 1.6+ to 60.5+ months) for pembrolizumab and 4.4 months (range 1.4+ to 63.1+ months) for chemotherapy; 36-month DOR rates were 44.4% and 28.3%, respectively. A total of 370 patients were enrolled in KEYNOTE-052. The median follow-up was 56.3 months (range 51.2-65.3 months; data cut-off 26 September 2020). The confirmed objective response rate was 28.9% (95% confidence interval 24.3-33.8), and the median DOR was 33.4 months (range 1.4+ to 60.7+ months); the 36-month DOR rate was 44.8%. Most treatment-related adverse events for pembrolizumab in either study were grade 1 or 2 and manageable, which is consistent with prior reports. Conclusion: With w5 years of follow-up, pembrolizumab monotherapy continued to demonstrate durable efficacy with no new safety signals in patients with platinum-resistant metastatic UC and as first-line therapy in cisplatin-ineligible patients.Clinical trial registry and ID: With ClinicalTrials.gov NCT02256436 (KEYNOTE-045); https://clinicaltrials.gov/ct2/show/ NCT02256436 and NCT02335424 (KEYNOTE-052); https://clinicaltrials.gov/ct2/show/NCT02335424

引用

页码：289 / 299

页数：11

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