KEYNOTE-361 evaluated first-line pembrolizumab with and without platinum-based chemotherapy
versus chemotherapy alone in advanced or metastatic urothelial carcinoma. The primary
end points of progression-free survival (PFS) or overall survival (OS) were not met.
Exploratory analysis of efficacy by platinum agent (cisplatin or carboplatin) is reported.Eligible
patients were randomly assigned 1:1:1 to receive pembrolizumab 200 mg intravenously
every 3 weeks for ≤35 cycles with or without chemotherapy (gemcitabine with investigator's
choice of either cisplatin or carboplatin) or chemotherapy alone. This exploratory
subset analysis evaluated PFS and objective response rate (ORR) per RECIST v1.1 by
blinded independent central review and OS for cisplatin- or carboplatin-based chemotherapy
with versus without pembrolizumab for patients assigned to chemotherapy-containing
arms of KEYNOTE-361.Of 1010 patients enrolled, 703 were assigned to receive a chemotherapy-containing
regimen (n = 312 cisplatin based; n = 391 carboplatin based). Median follow-up was
31.3 months. For cisplatin-based arms, with versus without pembrolizumab, median OS
was 20.1 versus 16.4 months (HR 0.88, 95% CI, 0.67-1.15) and median PFS was 8.5 versus
7.1 months (HR 0.67, 0.51-0.89). ORR was 64.1% versus 48.7%, respectively. For carboplatin-based
arms, with versus without pembrolizumab, median OS was 15.5 versus 12.3 months (HR
0.84, 95% CI, 0.67-1.06) and median PFS was 8.0 versus 6.7 months (HR 0.86, 0.68-1.09).
ORR was 47.2% versus 41.8%, respectively. Among patients in the cisplatin-based versus
carboplatin-based chemotherapy alone arms, 55.8% versus 41.8% received a subsequent
antiprogrammed cell death protein 1/ligand 1 therapy. The addition of pembrolizumab
did not significantly increase the incidence of adverse events reported.Results suggest
trends toward OS and PFS improvements with the addition of pembrolizumab to gemcitabine-platinum
doublet over gemcitabine-platinum alone regardless of whether cisplatin or carboplatin
was the chosen platinum agent. OS may have been influenced by active subsequent therapies.
