2023
106P Treatment sequencing in PD-L1–positive recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): Exploratory analysis of the phase III KEYNOTE-048 study
Greil R, Burtness B, Laban S, Braña I, Nin R, Fuereder T, Bratland Å, Licitra L, Rordorf T, Psyrri A, Popovtzer A, Hughes B, Tahara M, Lin J, Gumuscu B, Lerman N, Harrington K. 106P Treatment sequencing in PD-L1–positive recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): Exploratory analysis of the phase III KEYNOTE-048 study. Immuno-Oncology Technology 2023, 20: 100578. DOI: 10.1016/j.iotech.2023.100578.Peer-Reviewed Original ResearchRandomized Phase II Trial of Ficlatuzumab With or Without Cetuximab in Pan-Refractory, Recurrent/Metastatic Head and Neck Cancer
Bauman J, Saba N, Roe D, Bauman J, Kaczmar J, Bhatia A, Muzaffar J, Julian R, Wang S, Bearelly S, Baker A, Steuer C, Giri A, Burtness B, Centuori S, Caulin C, Klein R, Saboda K, Obara S, Chung C. Randomized Phase II Trial of Ficlatuzumab With or Without Cetuximab in Pan-Refractory, Recurrent/Metastatic Head and Neck Cancer. Journal Of Clinical Oncology 2023, 41: 3851-3862. PMID: 36977289, DOI: 10.1200/jco.22.01994.Peer-Reviewed Original ResearchConceptsMedian progression-free survivalProgression-free survivalObjective response rateRecurrent/metastatic headCMET overexpressionMetastatic headCombination armAntiepidermal growth factor receptor monoclonal antibodyNoncomparative phase II studyRecurrent/metastatic HNSCCRandomized phase II trialEnd pointNeck squamous cell carcinomaHPV negative subgroupPhase II studyPrimary end pointSecondary end pointsHPV-positive diseaseHuman papillomavirus (HPV) statusMajor prognostic factorPhase II trialKey eligibility criteriaSquamous cell carcinomaReceptor monoclonal antibodyHPV-negative HNSCC
2022
Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study
Harrington KJ, Burtness B, Greil R, Soulières D, Tahara M, de Castro G, Psyrri A, Brana I, Basté N, Neupane P, Bratland Å, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Ishak W, Lin J, Gumuscu B, Swaby RF, Rischin D. Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. Journal Of Clinical Oncology 2022, 41: 790-802. PMID: 36219809, PMCID: PMC9902012, DOI: 10.1200/jco.21.02508.Peer-Reviewed Original ResearchConceptsPD-L1 CPSNeck squamous cell carcinomaSquamous cell carcinomaRecurrent/metastatic headMetastatic headCell carcinomaOverall survivalNext-line therapyObjective response ratePembrolizumab-based therapyProgression-free survivalDeath ligand 1Long-term efficacyKEYNOTE-048Data cutoffSurvival benefitTotal populationMedian studyPembrolizumabResponse rateCarcinomaPositive scoreLigand 1Subsequent treatmentEfficacy658MO Pembrolizumab (pembro) vs standard-of-care (SOC) in previously treated recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): 6-year follow-up of KEYNOTE-040
Soulieres D, Harrington K, Le Tourneau C, Silva J, Licitra L, Ahn M, Soria A, Machiels J, Mach N, Mehra R, Burtness B, Lin J, Lerman N, Gumuscu B, Cohen E. 658MO Pembrolizumab (pembro) vs standard-of-care (SOC) in previously treated recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): 6-year follow-up of KEYNOTE-040. Annals Of Oncology 2022, 33: s843. DOI: 10.1016/j.annonc.2022.07.782.Peer-Reviewed Original Research659MO Pembrolizumab with or without chemotherapy for first-line treatment of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): 5-year results from KEYNOTE-048
Tahara M, Greil R, Rischin D, Harrington K, Burtness B, De Castro G, Psyrri A, Brana I, Neupane P, Bratland Å, Fuereder T, Hughes B, Nin R, Ngamphaiboon N, Rordorf T, Ishak W, Lin J, Gumuscu B, Lerman N, Soulieres D. 659MO Pembrolizumab with or without chemotherapy for first-line treatment of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): 5-year results from KEYNOTE-048. Annals Of Oncology 2022, 33: s844. DOI: 10.1016/j.annonc.2022.07.783.Peer-Reviewed Original ResearchA phase II/III trial of chemotherapy plus cetuximab versus chemotherapy plus bevacizumab versus atezolizumab plus bevacizumab following progression on immune checkpoint inhibition in recurrent/metastatic head and neck cancers: ECOG-ACRIN EA3202.
Bhatia A, Flamand Y, Johnson J, Ishizuka J, Duan F, Tang M, Karivedu V, Subramaniam R, Burtness B. A phase II/III trial of chemotherapy plus cetuximab versus chemotherapy plus bevacizumab versus atezolizumab plus bevacizumab following progression on immune checkpoint inhibition in recurrent/metastatic head and neck cancers: ECOG-ACRIN EA3202. Journal Of Clinical Oncology 2022, 40: tps6098-tps6098. DOI: 10.1200/jco.2022.40.16_suppl.tps6098.Peer-Reviewed Original ResearchProgression-free survivalVascular endothelial growth factorM HNSCCOverall survivalPrimary endpointExperimental armControl armHigher treatment-related adverse eventsPhase II/III trialsOne-sided alpha levelRecurrent/metastatic headTreatment-related adverse eventsEffector T cell responsesMyeloid-derived suppressor cellsPhase II/IIIPhase IIStratified log-rank testEfficacy of atezolizumabPlatinum-doublet chemotherapyImmune checkpoint inhibitionFirst-line pembrolizumabAnti-tumor immunityPhase IIIDendritic cell maturationPhase III evaluation
2021
438 A phase 1 trial of CUE-101, a novel HPV16 E7-pHLA-IL2-Fc fusion protein, alone and in combination with pembrolizumab in patients with recurrent/metastatic HPV16+ head and neck cancer
Chung C, Colevas A, Gibson M, Adkins D, Sukari A, Wirth L, Burtness B, Bauman J, Rodriguez C, Worden F, Saba N, Glisson B, Dunn L, Seiwert T, Agensky L, Levisetti M, Lynam R, Margossian S, Moniz R, Quayle S, Pienta K, Pai S. 438 A phase 1 trial of CUE-101, a novel HPV16 E7-pHLA-IL2-Fc fusion protein, alone and in combination with pembrolizumab in patients with recurrent/metastatic HPV16+ head and neck cancer. Journal For ImmunoTherapy Of Cancer 2021, 9: a468-a468. DOI: 10.1136/jitc-2021-sitc2021.438.Peer-Reviewed Original ResearchTreatment of HPV16Institutional review boardT cellsCombination cohortInterleukin-2HPV16 E7-specific CD8HPV16-specific T cellsPD-L1 tumor expressionRecurrent/metastatic headTumor-specific T cellsNeck squamous cell carcinomaAntigen-specific T cell activationSpecific T cell activationCTCAE grade 2Ongoing partial responsePhase 2 doseRECIST 1.1 criteriaAntitumor activityE7-specific CD8First-line treatmentAnti-tumor immunityPost-treatment biopsiesNatural killer cellsPhase 1 trialSquamous cell carcinomaP-88 First-Line Pembrolizumab With or Without Lenvatinib in Recurrent/Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC): Phase 3 LEAP-010 Study
Harrington K, Siu L, Burtness B, Cohen E, Licitra L, Rischin D, Zhu Y, Okpara C, Pinheiro C, Swaby R, Machiels J, Tahara M. P-88 First-Line Pembrolizumab With or Without Lenvatinib in Recurrent/Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC): Phase 3 LEAP-010 Study. Oral Oncology 2021, 118: 7-8. DOI: 10.1016/s1368-8375(21)00375-4.Peer-Reviewed Original ResearchP-94 Pembrolizumab plus lenvatinib vs chemotherapy and lenvatinib monotherapy for recurrent/metastatic head and neck squamous cell carcinoma that progressed on platinum therapy and immunotherapy: LEAP-009
Harrington K, Cohen E, Siu L, Rischin D, Licitra L, Vermorken J, Le Q, Tahara M, Machiels J, Hawk N, Ge J, Bidadi B, Swaby R, Burtness B. P-94 Pembrolizumab plus lenvatinib vs chemotherapy and lenvatinib monotherapy for recurrent/metastatic head and neck squamous cell carcinoma that progressed on platinum therapy and immunotherapy: LEAP-009. Oral Oncology 2021, 118: 10-11. DOI: 10.1016/s1368-8375(21)00381-x.Peer-Reviewed Original Research
2020
351 Pembrolizumab plus lenvatinib vs chemotherapy and lenvatinib monotherapy for recurrent/metastatic head and neck squamous cell carcinoma that progressed on platinum therapy and immunotherapy: LEAP-009
Harrington K, Cohen E, Siu L, Rischin D, Licitra L, Vermorken J, Le Q, Tahara M, Machiels J, Hawk N, Ge J, Bidadi B, Swaby R, Burtness B. 351 Pembrolizumab plus lenvatinib vs chemotherapy and lenvatinib monotherapy for recurrent/metastatic head and neck squamous cell carcinoma that progressed on platinum therapy and immunotherapy: LEAP-009. Journal For ImmunoTherapy Of Cancer 2020, 8: a376-a376. DOI: 10.1136/jitc-2020-sitc2020.0351.Peer-Reviewed Original ResearchPlatinum-based chemotherapyRecurrent/metastatic headNeck squamous cell carcinomaECOG performance statusSquamous cell carcinomaDisease progressionLenvatinib monotherapyM HNSCCCell carcinomaRECIST v1.1SOC chemotherapyMetastatic headMonotherapy armPerformance statusTreatment optionsPhase Ib/II trialStandard first-line treatment optionPD-L1 tumor proportion scoreFirst-line treatment optionAdvanced renal cell carcinomaJ Clin OncolSafety of pembrolizumabPD-1 inhibitorsPlatinum-containing chemotherapyAdvanced solid tumorsLEAP-010: Phase III study of first-line pembrolizumab with or without lenvatinib in patients (pts) with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC)
Siu L, Burtness B, Cohen E, Harrington K, Licitra L, Rischin D, Zhu Y, Okpara C, Pinheiro C, Swaby R, Machiels J, Tahara M. LEAP-010: Phase III study of first-line pembrolizumab with or without lenvatinib in patients (pts) with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Annals Of Oncology 2020, 31: s683-s684. DOI: 10.1016/j.annonc.2020.08.1088.Peer-Reviewed Original ResearchLong-term outcomes from KEYNOTE-048: Pembrolizumab (pembro) alone or with chemotherapy (pembro+C) vs EXTREME (E) as first-line (1L) therapy for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC)
Greil R, Rischin D, Harrington K, Soulières D, Tahara M, de Castro G, Psyrri A, Baste N, Neupane P, Bratland Å, Fuereder T, Hughes B, Mesia R, Ngamphaiboon N, Rordorf T, Ishak W, Lin J, Swaby R, Gumuscu B, Burtness B. Long-term outcomes from KEYNOTE-048: Pembrolizumab (pembro) alone or with chemotherapy (pembro+C) vs EXTREME (E) as first-line (1L) therapy for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Annals Of Oncology 2020, 31: s660-s661. DOI: 10.1016/j.annonc.2020.08.1030.Peer-Reviewed Original ResearchPembrolizumab (P) or P + chemotherapy (C) versus EXTREME (E) as first-line (1L) therapy for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): analysis of KEYNOTE-048 by disease state.
Rischin D, Harrington K, Greil R, Soulieres D, Tahara M, Castro G, Psyrri A, Baste N, Neupane P, Bratland Å, Fuereder T, Hughes B, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak W, Lin J, Gumuscu B, Swaby R, Burtness B. Pembrolizumab (P) or P + chemotherapy (C) versus EXTREME (E) as first-line (1L) therapy for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): analysis of KEYNOTE-048 by disease state. Journal Of Clinical Oncology 2020, 38: 6530-6530. DOI: 10.1200/jco.2020.38.15_suppl.6530.Peer-Reviewed Original ResearchTreatment-related adverse eventsIncurable recurrentMetastatic subgroupM HNSCCSuperior OSMedian OSPFS benefitGrade 3MS subgroupsRecurrent/metastatic headNeck squamous cell carcinomaKEYNOTE-048 trialPD-L1 CPSDisease statesECOG performance statusFirst-line therapyPD-L1 statusKaplan-Meier methodTotal study populationSquamous cell carcinomaCox regression modelKEYNOTE-048Metastatic headAdverse eventsHazard ratioRandomized, phase II study of ficlatuzumab with or without cetuximab in patients with pan-refractory, recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).
Bauman J, Roe D, Saba N, Bauman J, Kaczmar J, Burtness B, Muzaffar J, Julian R, Wang S, Bearelly S, Baker A, Steuer C, Bhatia A, Giri A, Caulin C, Stabile L, Centuori S, Chung C. Randomized, phase II study of ficlatuzumab with or without cetuximab in patients with pan-refractory, recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Journal Of Clinical Oncology 2020, 38: tps6594-tps6594. DOI: 10.1200/jco.2020.38.15_suppl.tps6594.Peer-Reviewed Original ResearchProgression-free survivalOverall response rateM HNSCCPhase II trialHepatocyte growth factorII trialCetuximab resistanceMulticenter phase II trialRecurrent/metastatic headTotal peripheral T cellsRandomized phase II trialExpression of HGFPoor progression-free survivalNeck squamous cell carcinomaPeripheral immune profileKey secondary endpointPhase II studyKey eligibility criteriaSquamous cell carcinomaPeripheral T cellsPI3K/AktIgG1 monoclonal antibodyTwo-arm designECOG 0EGFR monotherapyKEYNOTE-048: Progression after the next line of therapy following pembrolizumab (P) or P plus chemotherapy (P+C) vs EXTREME (E) as first-line (1L) therapy for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).
Harrington K, Rischin D, Greil R, Soulieres D, Tahara M, Castro G, Psyrri A, Baste N, Neupane P, Bratland Å, Fuereder T, Hughes B, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak W, Zhang Y, Gumuscu B, Swaby R, Burtness B. KEYNOTE-048: Progression after the next line of therapy following pembrolizumab (P) or P plus chemotherapy (P+C) vs EXTREME (E) as first-line (1L) therapy for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Journal Of Clinical Oncology 2020, 38: 6505-6505. DOI: 10.1200/jco.2020.38.15_suppl.6505.Peer-Reviewed Original ResearchPD-L1 CPSSubsequent anticancer therapyM HNSCCMedian PFS2Subsequent therapyRecurrent/metastatic headNeck squamous cell carcinomaNext-line therapyObjective tumor progressionImmune checkpoint inhibitorsFirst-line therapyKaplan-Meier methodAnticancer therapySquamous cell carcinomaCox regression modelTotal populationKEYNOTE-048Superior OSCheckpoint inhibitorsMetastatic headSystemic therapyComparable safetyCell carcinomaFavorable safetyPatient outcomesPhase III LEAP-010 study: first-line pembrolizumab with or without lenvatinib in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).
Siu L, Burtness B, Cohen E, Harrington K, Licitra L, Rischin D, Zhu Y, Lee C, Pinheiro C, Swaby R, Machiels J, Tahara M. Phase III LEAP-010 study: first-line pembrolizumab with or without lenvatinib in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Journal Of Clinical Oncology 2020, 38: tps6589-tps6589. DOI: 10.1200/jco.2020.38.15_suppl.tps6589.Peer-Reviewed Original ResearchBlinded independent central reviewCombined positive scoreFirst-line pembrolizumabM HNSCCDisease progressionRECIST v1.1PD-L1PD-L1 combined positive scoreECOG performance status 0PD-1 inhibitor pembrolizumabRecurrent/metastatic headEnd pointNeck squamous cell carcinomaCycles of pembrolizumabFirst-line monotherapyPerformance status 0Phase 1b/2 trialManageable safety profileObjective response ratePrimary end pointSecondary end pointsHuman papillomavirus (HPV) statusPD-L1 statusPhase 3 studyProgression-free survival
2019
Protocol-specified final analysis of the phase 3 KEYNOTE-048 trial of pembrolizumab (pembro) as first-line therapy for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC).
Rischin D, Harrington K, Greil R, Soulieres D, Tahara M, de Castro G, Psyrri A, Baste N, Neupane P, Bratland A, Fuereder T, Hughes B, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak W, Zhang Y, Jin F, Gumuscu B, Burtness B. Protocol-specified final analysis of the phase 3 KEYNOTE-048 trial of pembrolizumab (pembro) as first-line therapy for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Journal Of Clinical Oncology 2019, 37: 6000-6000. DOI: 10.1200/jco.2019.37.15_suppl.6000.Peer-Reviewed Original ResearchCombined positive scorePD-L1 combined positive scoreM HNSCCKEYNOTE-048Median DoRSuperior OSComparable safetyFavorable safetyRecurrent/metastatic headNeck squamous cell carcinomaKEYNOTE-048 trialSecond interim analysisFirst-line therapyPD-L1 testingPhase 3 studySquamous cell carcinomaTotal populationMetastatic headData cutoffSystemic therapyCell carcinomaE. ConclusionInterim analysisAE ratesTumor samples
2018
LBA8_PR KEYNOTE-048: Phase III study of first-line pembrolizumab (P) for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC)
Burtness B, Harrington K, Greil R, Soulières D, Tahara M, De Castro G, Psyrri A, Rotllan N, Neupane P, Bratland Å, Fuereder T, Hughes B, Mesia R, Ngamphaiboon N, Rordorf T, Ishak W, Roy A, Cheng J, Jin F, Rischin D. LBA8_PR KEYNOTE-048: Phase III study of first-line pembrolizumab (P) for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Annals Of Oncology 2018, 29: viii729. DOI: 10.1093/annonc/mdy424.045.Peer-Reviewed Original ResearchEfficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE-012
Mehra R, Seiwert TY, Gupta S, Weiss J, Gluck I, Eder JP, Burtness B, Tahara M, Keam B, Kang H, Muro K, Geva R, Chung HC, Lin CC, Aurora-Garg D, Ray A, Pathiraja K, Cheng J, Chow LQM, Haddad R. Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE-012. British Journal Of Cancer 2018, 119: 153-159. PMID: 29955135, PMCID: PMC6048158, DOI: 10.1038/s41416-018-0131-9.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedB7-H1 AntigenDrug-Related Side Effects and Adverse ReactionsFemaleFollow-Up StudiesGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateMaleMiddle AgedNeoplasm MetastasisNeoplasm Recurrence, LocalProgression-Free SurvivalSquamous Cell Carcinoma of Head and NeckConceptsTreatment-related adverse eventsNeck squamous cell carcinomaSquamous cell carcinomaAdverse eventsCell carcinomaDurable anti-tumor activityRecurrent/metastatic headRecurrent/metastatic HNSCCEfficacy of pembrolizumabSafety of pembrolizumabTolerable safety profileUse of pembrolizumabMedian response durationNon-randomised trialsOverall response rateCo-primary endpointsTreatment of HNSCCYears of treatmentAnti-tumor activityConclusionsSome patientsKEYNOTE-012MethodsMulti-centreGrade 3/4Metastatic headAdvanced headHealth-related quality of life (HRQoL) of pembrolizumab (pembro) vs standard of care (SOC) for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) in KEYNOTE-040.
Cohen E, Soulieres D, Le Tourneau C, Dinis J, Licitra L, Ahn M, Soria A, Machiels J, Mach N, Mehra R, Burtness B, Ellison M, Cheng J, Chirovsky D, Swaby R, Harrington K. Health-related quality of life (HRQoL) of pembrolizumab (pembro) vs standard of care (SOC) for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) in KEYNOTE-040. Journal Of Clinical Oncology 2018, 36: 6013-6013. DOI: 10.1200/jco.2018.36.15_suppl.6013.Peer-Reviewed Original Research