KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial
carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
- 27% reduction in the risk of death with KEYTRUDA vs chemotherapy (HR=0.73; 95% CI, 0.59–0.91; P=0.004).
- Number of deaths observed in each arm: 155/270 (57%) with KEYTRUDA vs 179/272 (66%) with chemotherapy
- Progression-free survival (PFS): There was no statistically significant difference in PFS with KEYTRUDA vs chemotherapy
(HR=0.98; 95% CI, 0.81–1.19; P=0.833).
- Number of events observed in each arm: 218/270 (81%) with KEYTRUDA vs 219/272 (81%) with chemotherapy.
- Median PFS was 2.1 months (95% CI, 2.0−2.2) with KEYTRUDA vs 3.3 months (95% CI, 2.3−3.5) with chemotherapy.
CI = confidence interval; HR = hazard ratio; OS = overall survival; PD-1 = programmed death receptor-1; Q3W = every 3 weeks; UC = urothelial carcinoma.
The phase 3 KEYNOTE-045 trial was stopped early due to superior overall survival with KEYTRUDA vs chemotherapy.1
ORR = objective response rate; CR = complete response; PR = partial response; NR = not reached.
- For all efficacy measures, the median follow-up time was 9.0 months (range: 0.2–20.8 months).
In second-line treatment of patients with locally advanced or metastatic urothelial carcinoma post–platinum failure
From Annals of Oncology, Y Fradet, J Bellmunt, D J Vaughn et al, 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. 2019; Vol 30(6), Pages 970–976. Reprinted by permission of Oxford University Press on behalf of the European Society for Medical Oncology. © The Author(s) 2019. All rights reserved.
- Limitations:
- The 2-year extension of KEYNOTE-045 was an exploratory analysis. No formal statistical testing was planned for the 2-year analysis and; therefore, no conclusions can be drawn.
- Estimates of the survival distribution were generated using the Kaplan-Meier method.
- Median follow-up time of 27.7 months
- 30% reduction in the risk of death with KEYTRUDA vs chemotherapy (HR=0.70; 95% CI, 0.57–0.85).3
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend pembrolizumab (KEYTRUDA) as a preferred category 1 subsequent systemic therapy option for locally advanced or metastatic UC post–platinum failure.4,a
aCategory 1 is based upon high-level evidence; there is uniform National Comprehensive Cancer Network® (NCCN®) consensus that the intervention is appropriate.4
NCCN makes no representations or warranties of any kind regarding their content, use or application and disclaims any responsibility for their application or use in any way.4
- Investigator’s choice of any of the following chemotherapy regimens given intravenously Q3W: paclitaxel 175 mg/m2, docetaxel
75 mg/m2, or vinflunine 320 mg/m2.
- Assessment of tumor status was performed at 9 weeks after randomization, then every 6 weeks through the first year, followed
by every 12 weeks thereafter.
- PFS and ORR were assessed by blinded independent central review (BICR) per Response Evaluation Criteria In Solid
Tumors (RECIST) v1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
- Patients with initial radiographic disease progression could receive additional doses of treatment during confirmation
of progression unless disease progression was symptomatic, was rapidly progressive, required urgent intervention,
or occurred with a decline in performance status.
- 15% of patients received treatment after disease progression following prior platinum-containing neoadjuvant or adjuvant
chemotherapy.
- The trial excluded patients with autoimmune disease or a medical condition that required immunosuppression.
For second-line patients with locally advanced or mUC, PD-L1 testing is not needed prior to use of KEYTRUDA.
PD-L1 = programmed death ligand 1.
- Median age: 66 (range: 26–88 years).
- 87% of patients had visceral metastases.
bAmong the 542 randomized patients, 74% were male; 72% were White and 23% were Asian; 96% had M1 disease and 4%
had M0 disease; 86% had a primary tumor in the lower tract and 14% had a primary tumor in the upper tract; 21% had received
≥2 prior systemic regimens in the metastatic setting.
cTwenty-three percent of patients had prior carboplatin therapy and 1% were treated with other platinum-based
regimens.
ECOG PS = Eastern Cooperative Oncology Group performance status.