2023
Lenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775
Makker V, Colombo N, Herráez A, Monk B, Mackay H, Santin A, Miller D, Moore R, Baron-Hay S, Ray-Coquard I, Ushijima K, Yonemori K, Kim Y, Alia E, Sanli U, Bird S, Orlowski R, McKenzie J, Okpara C, Barresi G, Lorusso D. Lenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775. Journal Of Clinical Oncology 2023, 41: 2904-2910. PMID: 37058687, PMCID: PMC10414727, DOI: 10.1200/jco.22.02152.Peer-Reviewed Original ResearchConceptsObjective response rateProgression-free survivalPrimary end pointAdvanced endometrial cancerOverall survivalEndometrial cancerEnd pointMismatch repair-proficient tumorsClinical trial updateMetastatic endometrial cancerNew safety signalsSubgroups of interestManageable safetyPrespecified analysisTrial updateProficient tumorsClinical trialsSafety signalsPembrolizumabLenvatinibPhysician's choiceMultiple end pointsResponse rateSecondary analysisChemotherapyHealth-Related Quality of Life in Patients With Advanced Endometrial Cancer Treated With Lenvatinib Plus Pembrolizumab or Treatment of Physician’s Choice
Lorusso D, Colombo N, Herraez A, Santin A, Colomba E, Miller D, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Kim Y, McCormack M, Massaad R, Nguyen A, Zhao Q, McKenzie J, Prabhu V, Makker V. Health-Related Quality of Life in Patients With Advanced Endometrial Cancer Treated With Lenvatinib Plus Pembrolizumab or Treatment of Physician’s Choice. European Journal Of Cancer 2023, 186: 172-184. PMID: 37086595, PMCID: PMC11003310, DOI: 10.1016/j.ejca.2023.03.015.Peer-Reviewed Original ResearchConceptsAdvanced endometrial cancerEndometrial cancerWeek 12Life QuestionnaireDefinitive deteriorationFunctional scalesPhysician's choiceGlobal health status/qualityFavorable benefit/risk profileHealth status/qualityBenefit/risk profileEuroQol-5 DimensionsHealth-related qualityTreatment of patientsTingling/numbnessImpact of treatmentQuality of lifeRate of completionHRQOL endpointsAppetite lossPoor body imageCancer QualityLife scoresMuscular painSafety results
2022
O018/#482 Updated safety of lenvatinib + pembrolizumab vs treatment of physician’s choice in patients with advanced endometrial cancer: study 309/keynote-775
Makker V, Colombo N, Herráez A, Monk B, Mackay H, Santin A, Miller D, Moore R, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Yonemori K, Kim Y, Alia E, Sanli U, Xie R, Zale M, Mckenzie J, Barresi G, Lorusso D. O018/#482 Updated safety of lenvatinib + pembrolizumab vs treatment of physician’s choice in patients with advanced endometrial cancer: study 309/keynote-775. 2022, a11-a11. DOI: 10.1136/ijgc-2022-igcs.20.Peer-Reviewed Original Research525MO Updated efficacy and safety of lenvatinib (LEN) + pembrolizumab (pembro) vs treatment of physician’s choice (TPC) in patients (pts) with advanced endometrial cancer (aEC): Study 309/KEYNOTE-775
Makker V, Colombo N, Herraez A, Monk B, Mackay H, Santin A, Miller D, Moore R, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Yonemori K, Kim Y, Alia E, Sanli U, Huang J, McKenzie J, Barresi G, Lorusso D. 525MO Updated efficacy and safety of lenvatinib (LEN) + pembrolizumab (pembro) vs treatment of physician’s choice (TPC) in patients (pts) with advanced endometrial cancer (aEC): Study 309/KEYNOTE-775. Annals Of Oncology 2022, 33: s785-s786. DOI: 10.1016/j.annonc.2022.07.653.Peer-Reviewed Original Research20MO Time to deterioration in quality of life in patients (pts) with advanced endometrial cancer (aEC) treated with lenvatinib plus pembrolizumab (L+P) or treatment of physician’s choice (TPC)
Lorusso D, Colombo N, Herraez A, Santin A, Colomba E, Miller D, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Kim Y, McCormack M, Massaad R, Nguyen A, Zhao Q, McKenzie J, Prabhu V, Makker V. 20MO Time to deterioration in quality of life in patients (pts) with advanced endometrial cancer (aEC) treated with lenvatinib plus pembrolizumab (L+P) or treatment of physician’s choice (TPC). Annals Of Oncology 2022, 33: s391-s392. DOI: 10.1016/j.annonc.2022.04.038.Peer-Reviewed Original ResearchEfficacy of next line of therapy after treatment with lenvatinib (LEN) in combination with pembrolizumab (pembro) versus treatment of physician’s choice (TPC) in patients (pts) with advanced endometrial cancer (aEC): Exploratory analysis of Study 309/KEYNOTE-775.
Makker V, Colombo N, Santin A, Miller D, Fujiwara K, Pignata S, Ray-Coquard I, Kim Y, Guerra E, Huang J, Barresi G, McKenzie J, Lorusso D. Efficacy of next line of therapy after treatment with lenvatinib (LEN) in combination with pembrolizumab (pembro) versus treatment of physician’s choice (TPC) in patients (pts) with advanced endometrial cancer (aEC): Exploratory analysis of Study 309/KEYNOTE-775. Journal Of Clinical Oncology 2022, 40: 5587-5587. DOI: 10.1200/jco.2022.40.16_suppl.5587.Peer-Reviewed Original ResearchAdvanced endometrial cancerComers populationTPC armEastern Cooperative Oncology Group performance statusPrior platinum-based chemotherapy regimenPlatinum-based chemotherapy regimenObjective response rateOverall survival benefitPrespecified exploratory analysisSystemic anticancer therapyPlatinum-based treatmentMedian PFS2PMMR tumorsChemotherapy regimenPelvic radiationData cutoffPerformance statusEndometrial cancerInvestigator assessmentSurvival benefitStudy treatmentMMR statusLenvatinibPembroPhysician's choiceLenvatinib plus Pembrolizumab for Advanced Endometrial Cancer
Makker V, Colombo N, Casado Herráez A, Santin AD, Colomba E, Miller DS, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Sakata J, Yonemori K, Kim YM, Guerra EM, Sanli UA, McCormack MM, Smith AD, Keefe S, Bird S, Dutta L, Orlowski RJ, Lorusso D. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer. New England Journal Of Medicine 2022, 386: 437-448. PMID: 35045221, DOI: 10.1056/nejmoa2108330.Peer-Reviewed Original ResearchConceptsAdvanced endometrial cancerProgression-free survivalEndometrial cancerOverall survivalMedian progression-free survivalPlatinum-based chemotherapy regimenLonger progression-free survivalEnd pointBlinded independent central reviewMedian overall survivalPrimary end pointPhase 3 trialResponse Evaluation CriteriaPlatinum-based chemotherapyIndependent central reviewChemotherapy regimenAdverse eventsStandard therapyCentral reviewPembrolizumabGrade 3LenvatinibChemotherapyPhysician's choicePatients
2021
O008/#785 A multicenter, open-label, randomized, phase 3 study to compare the efficacy and safety of lenvatinib in combination with pembrolizumab vs treatment of physician’s choice in patients with advanced endometrial cancer: study 309/keynote-775
Makker V, Colombo N, Herráez A, Santin A, Colomba E, Miller D, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira R, Ushijima K, Sakata J, Yonemori K, Kim Y, Guerra E, Sanli U, Mccormack M, Huang J, Smith A. O008/#785 A multicenter, open-label, randomized, phase 3 study to compare the efficacy and safety of lenvatinib in combination with pembrolizumab vs treatment of physician’s choice in patients with advanced endometrial cancer: study 309/keynote-775. International Journal Of Gynecological Cancer 2021, 31: a4-a5. DOI: 10.1136/ijgc-2021-igcs.8.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsAdvanced endometrial cancerObjective response rateEndometrial cancerPhysician's choiceCommon treatment-emergent adverse eventsPrior platinum-based chemotherapy regimenPhase 3 study resultsPlatinum-based chemotherapy regimenPrior platinum-based chemotherapyDNA mismatch repair (MMR) statusBlinded independent central reviewPhase 1b/2 studySafety of lenvatinibKey secondary endpointMedian treatment durationAdvanced endometrial carcinomaPhase 3 studyPlatinum-based chemotherapyIndependent central reviewPlatinum-based therapyMismatch repair statusEligible ptsRECIST v1.1Adjuvant setting145 Characterization of adverse reactions in patients with advanced endometrial cancer (aec) receiving lenvatinib + pembrolizumab (Study 309/KEYNOTE-775)
Colombo N, Lorusso D, Santin A, Kim Y, Herráez A, Yonemori K, Fujiwara K, Colomba E, Miller D, Pignata S, Monk B, Guerra E, Kristeleit R, Orlando M, Sanli U, Dutta L, Orlowski R, Ren M, Makker V. 145 Characterization of adverse reactions in patients with advanced endometrial cancer (aec) receiving lenvatinib + pembrolizumab (Study 309/KEYNOTE-775). International Journal Of Gynecological Cancer 2021, 31: a78-a78. DOI: 10.1136/ijgc-2021-esgo.120.Peer-Reviewed Original ResearchPalmar-plantar erythrodysesthesiaLenvatinib dose reductionAdverse reactionsMusculoskeletal painDose reductionPrior platinum-based therapyAEC patientsTarget lesion diametersCommon adverse reactionsAdvanced endometrial cancerManagement of patientsPlatinum-based therapyQd poEndometrial cancerTreatment initiationMedian timeEndometrial carcinomaHypertensionLenvatinibPrompt identificationPhysician's choiceDiarrheaPatientsFirst onsetMeaningful improvements726MO Outcomes by histology and prior therapy with lenvatinib plus pembrolizumab vs treatment of physician’s choice in patients with advanced endometrial cancer (Study 309/KEYNOTE-775)
Colombo N, Lorusso D, Herráez A, Santin A, Colomba E, Miller D, Fujiwara K, Pignata S, Floquet A, Monk B, Banerjee S, Penson R, Kristeleit R, Fabbro M, Orlando M, Mackay H, Jensen E, Dutta L, Orlowski R, Makker V. 726MO Outcomes by histology and prior therapy with lenvatinib plus pembrolizumab vs treatment of physician’s choice in patients with advanced endometrial cancer (Study 309/KEYNOTE-775). Annals Of Oncology 2021, 32: s729-s730. DOI: 10.1016/j.annonc.2021.08.1169.Peer-Reviewed Original ResearchA multicenter, open-label, randomized, phase III study to compare the efficacy and safety of lenvatinib in combination with pembrolizumab versus treatment of physician's choice in patients with advanced endometrial cancer
Makker V, Colombo N, Herráez A, Santin A, Colomba E, Miller D, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Sakata J, Yonemori K, Kim Y, Guerra E, Sanli U, McCormack M, Huang J, Smith A, Keefe S, Dutta L, Orlowski R, Lorusso D. A multicenter, open-label, randomized, phase III study to compare the efficacy and safety of lenvatinib in combination with pembrolizumab versus treatment of physician's choice in patients with advanced endometrial cancer. Gynecologic Oncology 2021, 162: s4. DOI: 10.1016/s0090-8258(21)00657-0.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsAdvanced endometrial cancerObjective response rateEndometrial cancerPhysician's choiceCommon treatment-emergent adverse eventsGrade treatment-emergent adverse eventsPrior platinum-based chemotherapy regimenPhase III study resultsPlatinum-based chemotherapy regimenPrior platinum-based chemotherapyDNA mismatch repair (MMR) statusBlinded independent central reviewPhase 1b/2 studySafety of lenvatinibKey secondary endpointMedian treatment durationAdvanced endometrial carcinomaPlatinum-based chemotherapyIndependent central reviewPlatinum-based therapyMismatch repair statusAdjuvant settingChemotherapy regimenECOG PS