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

Y. Fradet, J. Bellmunt, D. J. Vaughn, J. L. Lee, L. Fong, N. J. Vogelzang, M. A. Climent, D. P. Petrylak, T. K. Choueiri, A. Necchi, W. Gerritsen, H. Gurney, D. I. Quinn, S. Culine, C. N. Sternberg, K. Nam, T. L. Frenkl, R. F. Perini, R. De Wit, D. F. Bajorin

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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 [200 mg every 3 weeks (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 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 27.7 months. 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 (4.4 months; 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.

LanguageEnglish
Article numbermdz127
Pages970-976
Number of pages7
JournalAnnals of Oncology
Volume30
Issue number6
Early online date3 May 2019
DOIs
Publication statusPublished - 1 Jun 2019

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docetaxel
Paclitaxel
Drug Therapy
Neoplasms
Platinum
Disease-Free Survival
Survival Rate
Radiology
Safety
pembrolizumab
vinflunine
Survival

Bibliographical note

Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • PD-1
  • PD-L1
  • pembrolizumab
  • urothelial cancer

Cite this

Fradet, Y. ; Bellmunt, J. ; Vaughn, D. J. ; Lee, J. L. ; Fong, L. ; Vogelzang, N. J. ; Climent, M. A. ; Petrylak, D. P. ; Choueiri, T. K. ; Necchi, A. ; Gerritsen, W. ; Gurney, H. ; Quinn, D. I. ; Culine, S. ; Sternberg, C. N. ; Nam, K. ; Frenkl, T. L. ; Perini, R. F. ; De Wit, R. ; Bajorin, D. F. / 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. In: Annals of Oncology. 2019 ; Vol. 30, No. 6. pp. 970-976.
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title = "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",
abstract = "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 [200 mg every 3 weeks (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 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 27.7 months. 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 (4.4 months; 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.",
keywords = "PD-1, PD-L1, pembrolizumab, urothelial cancer",
author = "Y. Fradet and J. Bellmunt and Vaughn, {D. J.} and Lee, {J. L.} and L. Fong and Vogelzang, {N. J.} and Climent, {M. A.} and Petrylak, {D. P.} and Choueiri, {T. K.} and A. Necchi and W. Gerritsen and H. Gurney and Quinn, {D. I.} and S. Culine and Sternberg, {C. N.} and K. Nam and Frenkl, {T. L.} and Perini, {R. F.} and {De Wit}, R. and Bajorin, {D. F.}",
note = "Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",
year = "2019",
month = "6",
day = "1",
doi = "10.1093/annonc/mdz127",
language = "English",
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Fradet, Y, Bellmunt, J, Vaughn, DJ, Lee, JL, Fong, L, Vogelzang, NJ, Climent, MA, Petrylak, DP, Choueiri, TK, Necchi, A, Gerritsen, W, Gurney, H, Quinn, DI, Culine, S, Sternberg, CN, Nam, K, Frenkl, TL, Perini, RF, De Wit, R & Bajorin, DF 2019, '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', Annals of Oncology, vol. 30, no. 6, mdz127, pp. 970-976. https://doi.org/10.1093/annonc/mdz127

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. / Fradet, Y.; Bellmunt, J.; Vaughn, D. J.; Lee, J. L.; Fong, L.; Vogelzang, N. J.; Climent, M. A.; Petrylak, D. P.; Choueiri, T. K.; Necchi, A.; Gerritsen, W.; Gurney, H.; Quinn, D. I.; Culine, S.; Sternberg, C. N.; Nam, K.; Frenkl, T. L.; Perini, R. F.; De Wit, R.; Bajorin, D. F.

In: Annals of Oncology, Vol. 30, No. 6, mdz127, 01.06.2019, p. 970-976.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer

T2 - Annals of Oncology

AU - Fradet, Y.

AU - Bellmunt, J.

AU - Vaughn, D. J.

AU - Lee, J. L.

AU - Fong, L.

AU - Vogelzang, N. J.

AU - Climent, M. A.

AU - Petrylak, D. P.

AU - Choueiri, T. K.

AU - Necchi, A.

AU - Gerritsen, W.

AU - Gurney, H.

AU - Quinn, D. I.

AU - Culine, S.

AU - Sternberg, C. N.

AU - Nam, K.

AU - Frenkl, T. L.

AU - Perini, R. F.

AU - De Wit, R.

AU - Bajorin, D. F.

N1 - Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2019/6/1

Y1 - 2019/6/1

N2 - 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 [200 mg every 3 weeks (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 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 27.7 months. 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 (4.4 months; 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.

AB - 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 [200 mg every 3 weeks (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 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 27.7 months. 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 (4.4 months; 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.

KW - PD-1

KW - PD-L1

KW - pembrolizumab

KW - urothelial cancer

UR - http://www.scopus.com/inward/record.url?scp=85071011751&partnerID=8YFLogxK

U2 - 10.1093/annonc/mdz127

DO - 10.1093/annonc/mdz127

M3 - Article

VL - 30

SP - 970

EP - 976

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 6

M1 - mdz127

ER -