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Clin Genitourin Cancer. 2018 Dec;16(6):421-428.e1. doi: 10.1016/j.clgc.2018.07.004. Epub 2018 Jul 12.

Pembrolizumab Combined With Either Docetaxel or Gemcitabine in Patients With Advanced or Metastatic Platinum-Refractory Urothelial Cancer: Results From a Phase I Study.

Author information

1
Division of Hematology Oncology, University of California Davis Comprehensive Cancer Center, Sacramento, CA. Electronic address: mbparikh@ucdavis.edu.
2
Division of Hematology Oncology, University of California Davis Comprehensive Cancer Center, Sacramento, CA.
3
Division of Biostatistics, University of California Davis School of Medicine, Davis, CA.
4
Office of Clinical Research, University of California Davis Comprehensive Cancer Center, Sacramento, CA.

Abstract

INTRODUCTION:

Cytotoxic chemotherapy might prime urothelial cancer (UC) to checkpoint inhibition, prompting a trial of chemotherapy with the programmed death receptor-1 inhibitor pembrolizumab.

PATIENTS AND METHODS:

Patients with advanced, platinum-refractory UC received pembrolizumab and either docetaxel (arm A) or gemcitabine (arm B). Primary end points were assessments of maximum tolerated dose and dose-limiting toxicity (DLT). Secondary end points were overall response rate (ORR) and progression-free survival (PFS).

RESULTS:

Twelve patients were enrolled in the initial cohorts; 6 in each arm. One DLT was seen in each arm: Grade 3 hypophosphatemia (arm A), Grade 3 diarrhea (arm B). Adverse events of Grade >3 were observed in 7 (54%), the most common being anemia (6; 50%), fatigue (6; 50%), hyponatremia (4; 33%) and neutropenia (3; 25%), with no treatment-related deaths. There were 5 confirmed responses (1 complete, 4 partial), with an ORR of 42% and disease control rate (DCR) of 58%. Arm A had an ORR of 50% and DCR of 67%, whereas arm B had an ORR of 33% and DCR of 50%. Median PFS was 4.8, 5.7, and 3.7 months for the overall cohort, arm A, and arm B, respectively.

CONCLUSION:

Pembrolizumab with either docetaxel or gemcitabine is feasible for treatment of platinum-refractory advanced UC patients. Preliminary efficacy was observed. Further examination is warranted.

KEYWORDS:

Checkpoint inhibition; Chemotherapy; Immunotherapy; Platinum-refractory; Urothelial Carcinoma

PMID:
30166228
PMCID:
PMC6450697
[Available on 2019-12-01]
DOI:
10.1016/j.clgc.2018.07.004
[Indexed for MEDLINE]

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