2022
Efficacy and safety of pembrolizumab in metastatic urothelial carcinoma: results from KEYNOTE-045 and KEYNOTE-052 after up to 5 years of follow-up ☆
Balar A, Castellano D, Grivas P, Vaughn D, Powles T, Vuky J, Fradet Y, Lee J, Fong L, Vogelzang N, Climent M, Necchi A, Petrylak D, Plimack E, Xu J, Imai K, Moreno B, Bellmunt J, de Wit R, O’Donnell P. Efficacy and safety of pembrolizumab in metastatic urothelial carcinoma: results from KEYNOTE-045 and KEYNOTE-052 after up to 5 years of follow-up ☆. Annals Of Oncology 2022, 34: 289-299. PMID: 36494006, DOI: 10.1016/j.annonc.2022.11.012.Peer-Reviewed Original ResearchConceptsMetastatic urothelial carcinomaBlinded independent central reviewCisplatin-ineligible patientsObjective response rateRECIST version 1.1Years of followUrothelial carcinomaKEYNOTE-045KEYNOTE-052Primary endpointMost treatment-related adverse eventsResponse rateSurvival rateConfirmed objective response rateTreatment-related adverse eventsProgression-free survival ratesFurther safety concernsPlatinum-containing chemotherapyFirst-line therapyImmune checkpoint inhibitorsNew safety signalsProgression-free survivalDurability of responseFirst-line pembrolizumabOverall survival rateImpact of primary tumor location on efficacy and safety of pembrolizumab (pembro) in patients (pts) with locally advanced or metastatic urothelial carcinoma (UC) enrolled in the phase 2 KEYNOTE-052 and phase 3 KEYNOTE-045 trials.
O'Donnell P, Balar A, Castellano D, De Wit R, Vaughn D, Powles T, Vuky J, Lee J, Fradet Y, Bellmunt J, Fong L, Petrylak D, Gerritsen W, Quinn D, Culine S, Bajorin D, Xu J, Imai K, Moreno B, Grivas P. Impact of primary tumor location on efficacy and safety of pembrolizumab (pembro) in patients (pts) with locally advanced or metastatic urothelial carcinoma (UC) enrolled in the phase 2 KEYNOTE-052 and phase 3 KEYNOTE-045 trials. Journal Of Clinical Oncology 2022, 40: 516-516. DOI: 10.1200/jco.2022.40.6_suppl.516.Peer-Reviewed Original ResearchMetastatic urothelial carcinomaPrimary tumor locationKEYNOTE-045KEYNOTE-052Urothelial carcinomaTumor locationRECIST v1.1Primary tumorSafety of pembrolizumabSimilar clinical activityWithdrawal of consentMeasurable diseaseData cutoffManageable safetyUnacceptable toxicitySystemic therapyPD-L1Positive tumorsRenal pelvisDisease progressionPembroSimilar efficacyClinical activityGrade 3UT group
2021
Pembrolizumab (pembro) versus investigator’s choice of paclitaxel, docetaxel, or vinflunine in recurrent, advanced urothelial cancer (UC): 5-year follow-up from the phase 3 KEYNOTE-045 trial.
Bellmunt J, Necchi A, De Wit R, Lee J, Fong L, Vogelzang N, Durán M, Petrylak D, Choueiri T, Gerritsen W, Gurney H, Quinn D, Culine S, Sternberg C, Xu J, Moreno B, Godwin J, Bajorin D, Vaughn D, Fradet Y. Pembrolizumab (pembro) versus investigator’s choice of paclitaxel, docetaxel, or vinflunine in recurrent, advanced urothelial cancer (UC): 5-year follow-up from the phase 3 KEYNOTE-045 trial. Journal Of Clinical Oncology 2021, 39: 4532-4532. DOI: 10.1200/jco.2021.39.15_suppl.4532.Peer-Reviewed Original ResearchDuration of responseMetastatic urothelial cancerUrothelial cancerKEYNOTE-045Median OSOS benefitInvestigator's choiceKey secondary end pointMedian DOREnd pointAdvanced urothelial cancerECOG PS 0Platinum-containing regimenPrimary end pointSecondary end pointsTreatment-related AEsPhase 3 trialYears of therapyRECIST v1.1Baseline hemoglobinECOG PSMeasurable diseaseOS ratesPrior therapyData cutoff
2020
Association of TMB with efficacy of pembrolizumab (pembro) in patients (pts) with advanced urothelial cancer (UC): Results from KEYNOTE-045 and KEYNOTE-052
Bellmunt J, de Wit R, Fradet Y, Climent M, Petrylak D, Lee J, Fong L, Necchi A, Sternberg C, Grivas P, O’Donnell P, Powles T, Plimack E, Cristescu R, Lunceford J, Ma J, Rajasagi M, Godwin J, Moreno B, Bajorin D. Association of TMB with efficacy of pembrolizumab (pembro) in patients (pts) with advanced urothelial cancer (UC): Results from KEYNOTE-045 and KEYNOTE-052. Annals Of Oncology 2020, 31: s580-s581. DOI: 10.1016/j.annonc.2020.08.819.Peer-Reviewed Original Research
2018
901P Impact of prognostic factors and risk groups on overall survival (OS) in patients treated with pembrolizumab vs investigator’s choice chemotherapy for advanced urothelial cancer (UC): Post hoc analysis of KEYNOTE-045
Bellmunt J, de Wit R, Vaughn D, Fradet Y, Lee J, Fong L, Vogelzang N, Climent M, Petrylak D, Choueiri T, Necchi A, Gerritsen W, Gurney H, Quinn D, Culine S, Sternberg C, Jensen E, Frenkl T, Perini R, Bajorin D. 901P Impact of prognostic factors and risk groups on overall survival (OS) in patients treated with pembrolizumab vs investigator’s choice chemotherapy for advanced urothelial cancer (UC): Post hoc analysis of KEYNOTE-045. Annals Of Oncology 2018, 29: viii320-viii321. DOI: 10.1093/annonc/mdy283.110.Peer-Reviewed Original Research
2017
Planned survival analysis from KEYNOTE-045: Phase 3, open-label study of pembrolizumab (pembro) versus paclitaxel, docetaxel, or vinflunine in recurrent, advanced urothelial cancer (UC).
Bajorin D, De Wit R, Vaughn D, Fradet Y, Lee J, Fong L, Vogelzang N, Climent M, Petrylak D, Choueiri T, Necchi A, Gerritsen W, Gurney H, Quinn D, Culine S, Sternberg C, Mai Y, Puhlmann M, Perini R, Bellmunt J. Planned survival analysis from KEYNOTE-045: Phase 3, open-label study of pembrolizumab (pembro) versus paclitaxel, docetaxel, or vinflunine in recurrent, advanced urothelial cancer (UC). Journal Of Clinical Oncology 2017, 35: 4501-4501. DOI: 10.1200/jco.2017.35.15_suppl.4501.Peer-Reviewed Original ResearchAdvanced urothelial cancerUrothelial cancerSurvival analysisPrimary efficacy end pointEnd pointECOG PS 0Efficacy end pointSecond-line chemotherapyTreatment-related AEsOpen-label studySecondary end pointsPD-L1 expressionSuperior safety profileECOG PSKEYNOTE-045Measurable diseaseOS benefitMedian OSPrior therapyBaseline characteristicsLonger OSMedian durationPS 0Systemic therapyLiver metastasesHealth-related quality of life (HRQoL) of pembrolizumab (pembro) vs chemotherapy (chemo) for previously treated advanced urothelial cancer (UC) in KEYNOTE-045.
De Wit R, Bajorin D, Bellmunt J, Fradet Y, Lee J, Fong L, Vogelzang N, Climent M, Petrylak D, Choueiri T, Necchi A, Gerritsen W, Gurney H, Quinn D, Culine S, Sternberg C, Mai Y, Li H, Perini R, Vaughn D. Health-related quality of life (HRQoL) of pembrolizumab (pembro) vs chemotherapy (chemo) for previously treated advanced urothelial cancer (UC) in KEYNOTE-045. Journal Of Clinical Oncology 2017, 35: 4530-4530. DOI: 10.1200/jco.2017.35.15_suppl.4530.Peer-Reviewed Original ResearchAdvanced urothelial cancerGlobal health status/QoL scoreUrothelial cancerKEYNOTE-045HRQoL instrumentsQOL scoresWk 15Cox proportional hazards modelStratified log-rank testHRQOL end pointsSecond-line therapyTreatment-related AEsHealth-related qualityLog-rank testProportional hazards modelSuperior OSBetter HRQoLHRQoL analysisStudy treatmentPembroHazards modelInvestigator's choiceRate of improvementLongitudinal data analysis modelEnd pointHealth-related quality of life (HRQoL) in the KEYNOTE-045 study of pembrolizumab versus investigator-choice chemotherapy for previously treated advanced urothelial cancer.
Vaughn D, Bellmunt J, De Wit R, Fradet Y, Lee J, Fong L, Vogelzang N, Climent M, Petrylak D, Choueiri T, Necchi A, Gerritsen W, Gurney H, Quinn D, Culine S, Sternberg C, Mai Y, Li H, Perini R, Bajorin D. Health-related quality of life (HRQoL) in the KEYNOTE-045 study of pembrolizumab versus investigator-choice chemotherapy for previously treated advanced urothelial cancer. Journal Of Clinical Oncology 2017, 35: 282-282. DOI: 10.1200/jco.2017.35.6_suppl.282.Peer-Reviewed Original ResearchGlobal health status/QoL scoreAdvanced UCKEYNOTE-045HRQoL instrumentsQOL scoresWk 15Cox proportional hazards modelStratified log-rank testAdvanced urothelial cancerHRQOL end pointsInvestigator-choice chemotherapySecond-line therapyTreatment-related AEsHealth-related qualityLog-rank testProportional hazards modelSuperior OSBetter HRQoLHRQoL analysisUrothelial cancerStudy treatmentPembroHazards modelInvestigator's choiceRate of improvement