Cisplatin- or Carboplatin-Based Chemotherapy Plus Pembrolizumab in Advanced Urothelial Cancer: Exploratory Analysis From the Phase 3 KEYNOTE-361 Study

Abstract

IntroductionKEYNOTE-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. Patients and MethodsEligible 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. ResultsOf 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 anti–programmed cell death protein 1/ligand 1 therapy. The addition of pembrolizumab did not significantly increase the incidence of adverse events reported. ConclusionResults suggest trends towards 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. MicroAbstractUntil recently, the standard first-line treatment for advanced urothelial carcinoma included platinum-based chemotherapy containing either cisplatin or carboplatin. This exploratory analysis from the KEYNOTE-361 study describes efficacy outcomes with the addition of pembrolizumab to cisplatin- or carboplatin-based chemotherapy to determine if there are differences in clinical benefit between patients who received cisplatin-based versus carboplatin-based combination therapy.