2024
Pembrolizumab Plus Carboplatin and Paclitaxel as First-Line Therapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE-B10): A Single-Arm Phase IV Trial
Dzienis M, Cundom J, Fuentes C, Spreafico A, Nordlinger M, Pastor A, Alesi E, Neki A, Fung A, Lima I, Oppelt P, da Cunha G, Burtness B, Franke F, Tseng J, Joshi A, McCarthy J, Swaby R, Sidi Y, Gumuscu B, Naicker N, de Castro G. Pembrolizumab Plus Carboplatin and Paclitaxel as First-Line Therapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE-B10): A Single-Arm Phase IV Trial. Journal Of Clinical Oncology 2024, 42: 2989-2999. PMID: 39038265, PMCID: PMC11361359, DOI: 10.1200/jco.23.02625.Peer-Reviewed Original ResearchBlinded independent central reviewRecurrent/metastatic head and neck squamous cell carcinomaHead and neck squamous cell carcinomaNeck squamous cell carcinomaR/M HNSCCSquamous cell carcinomaRECIST v1.1Cell carcinomaSingle-armStandard-of-care first-line treatmentSafety of first-line pembrolizumabEastern Cooperative Oncology Group performance statusDay 1Treatment-related adverse eventsAlternative chemotherapy combinationsFirst-line pembrolizumabPD-L1 statusMedian follow-upFirst-line therapyIndependent central reviewFirst-line treatmentPhase IV trialChemotherapy combinationsComplete responsePD-L1
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 Research
2022
Current Therapy for Metastatic Head and Neck Cancer: Evidence, Opportunities, and Challenges.
Wise-Draper TM, Bahig H, Tonneau M, Karivedu V, Burtness B. Current Therapy for Metastatic Head and Neck Cancer: Evidence, Opportunities, and Challenges. American Society Of Clinical Oncology Educational Book 2022, 42: 1-14. PMID: 35486888, DOI: 10.1200/edbk_350442.Peer-Reviewed Original ResearchConceptsNeck squamous cell carcinomaSquamous cell carcinomaMetastatic headCell carcinomaSystemic therapyFirst-line systemic therapyFirst-line immunotherapyInclusion of chemotherapyImmune checkpoint blockadeNew systemic therapiesNumber of patientsAggressive local managementCombination immunotherapyLocoregional therapyOligometastatic diseaseCheckpoint blockadeNovel immunotherapiesPD-L1Lung metastasesRetrospective studyBiomarker subgroupsCurrent therapiesNeck cancerAblative approachesAntiangiogenic agentsPhase 1/2 study of pepinemab, an inhibitor of semaphorin 4D, in combination with pembrolizumab as first-line treatment of recurrent or metastatic head and neck cancer (KEYNOTE-B84).
Fisher T, Evans E, Mallow C, Foster A, Boise M, Smith E, Leonard J, Chaney M, Beck J, Hager S, Mekhail T, Seetharamu N, Baumgart M, Saba N, Steuer C, Adkins D, Burtness B, Zauderer M. Phase 1/2 study of pepinemab, an inhibitor of semaphorin 4D, in combination with pembrolizumab as first-line treatment of recurrent or metastatic head and neck cancer (KEYNOTE-B84). Journal Of Clinical Oncology 2022, 40: e18033-e18033. DOI: 10.1200/jco.2022.40.16_suppl.e18033.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsFirst-line treatmentDose-expansion phaseM HNSCCComplete responsePD-L1Tumor microenvironmentClinical benefitSingle-arm open-label studyPrior immune checkpoint inhibitorsNeck squamous cell carcinomaSemaphorin 4DActivation of DCsExploratory biomarker analysisImmunosuppressive myeloid cellsTumor PD-L1Open-label studyPrimary efficacy endpointSquamous cell carcinomaPK/PDBiomarker analysisECOG 0Measurable diseaseTreatment biopsiesCheckpoint inhibitorsPhase 1/2 Study of Pepinemab in Combination with Pembrolizumab as First-Line Treatment of Advanced, Recurrent or Metastatic Head and Neck Cancer (KEYNOTE B84)
Fisher T, Evans E, Mallow C, Foster A, Boise M, Smith E, Leonard J, Chaney M, Beck J, Hager S, Saba N, Steuer C, Adkins D, Burtness B, Zauderer M. Phase 1/2 Study of Pepinemab in Combination with Pembrolizumab as First-Line Treatment of Advanced, Recurrent or Metastatic Head and Neck Cancer (KEYNOTE B84). International Journal Of Radiation Oncology • Biology • Physics 2022, 112: e36. DOI: 10.1016/j.ijrobp.2021.12.084.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsDose-expansion phaseFirst-line treatmentM HNSCCTumor microenvironmentPD-L1Clinical benefitT cellsSingle-arm open-label studyPrior immune checkpoint inhibitorsMore effective treatment optionsNeck squamous cell carcinomaActivation of DCsActivity of pembrolizumabExploratory biomarker analysisImmunosuppressive myeloid cellsTumor PD-L1Open-label studyPrimary efficacy endpointDuration of responseEffective treatment optionSquamous cell carcinomaClear unmet needPK/PDMore effective treatments
2020
71P A phase II study of ADU-S100 in combination with pembrolizumab in adult patients with PD-L1+ recurrent or metastatic HNSCC: Preliminary safety, efficacy and PK/PD results
Zandberg D, Ferris R, Laux D, Mehra R, Nabell L, Kaczmar J, Gibson M, Kim Y, Neupane P, Bauman J, Julian R, Adkins D, Cohen E, Burtness B, Bermingham C, Dupage A, Desbien A, Loi A, Nuyten D, Saba N. 71P A phase II study of ADU-S100 in combination with pembrolizumab in adult patients with PD-L1+ recurrent or metastatic HNSCC: Preliminary safety, efficacy and PK/PD results. Annals Of Oncology 2020, 31: s1446-s1447. DOI: 10.1016/j.annonc.2020.10.559.Peer-Reviewed Original ResearchPhase 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
Immunotherapy for head and neck cancer: Recent advances and future directions
Cramer JD, Burtness B, Ferris RL. Immunotherapy for head and neck cancer: Recent advances and future directions. Oral Oncology 2019, 99: 104460. PMID: 31683169, PMCID: PMC7749717, DOI: 10.1016/j.oraloncology.2019.104460.Peer-Reviewed Original ResearchConceptsM HNSCCPembrolizumab monotherapyPD-L1Clinical trialsAnti-PD1 antibody nivolumabPhase III randomized trialsRandomized phase III trialCo-stimulatory agonistsImmune cell stainingInvestigator-choice chemotherapyPD-L1 CPSPhase III trialsRecurrent/metastaticDetailed clinical dataEXTREME regimenKEYNOTE-048Advanced diseaseCheckpoint inhibitorsIII trialsProlong survivalAntibody nivolumabRandomized trialsTherapeutic vaccinesNeck cancerTherapeutic advances1115PD Analysis of efficacy outcomes based on programmed death ligand 1 (PD-L1) scoring techniques in patients with head and neck squamous cell carcinoma (HNSCC) from KEYNOTE-040
Cohen E, Harrington K, Soulières D, Le Tourneau C, Licitra L, Burtness B, Bal T, Juco J, Aurora-Garg D, Huang L, Swaby R, Emancipator K. 1115PD Analysis of efficacy outcomes based on programmed death ligand 1 (PD-L1) scoring techniques in patients with head and neck squamous cell carcinoma (HNSCC) from KEYNOTE-040. Annals Of Oncology 2019, 30: v452-v453. DOI: 10.1093/annonc/mdz252.007.Peer-Reviewed Original ResearchTumor proportion scoreSecond-line treatmentSubsidiary of MerckMerck SeronoPD-L1Dohme Corp.Boehringer IngelheimTrial conductEfficacy outcomesMerck SharpEfficacy resultsDeath ligand 1 (PD-L1) expressionNeck squamous cell carcinomaGenentech/RocheObjective response rateSecond-line therapyLigand 1 expressionPD-L1 expressionPD-L1 statusProgression-free survivalSquamous cell carcinomaStandard of careSimilar survival resultsExpression levelsEuropean Medicines Agency
2017
IDO1 as a mechanism of adaptive immune resistance to anti-PD1 monotherapy in HNSCC.
Wirth L, Burtness B, Mehra R, Bauman J, Lee J, Smith N, Lefranc-Torres A, Westra W, Bishop J, Faquin W, Lin D, Pai S. IDO1 as a mechanism of adaptive immune resistance to anti-PD1 monotherapy in HNSCC. Journal Of Clinical Oncology 2017, 35: 6053-6053. DOI: 10.1200/jco.2017.35.15_suppl.6053.Peer-Reviewed Original ResearchHPV- HNSCCsPD-L1Clinical responseHNSCC patientsResponse rateAnti-PD-1 monotherapyAnti-PD-1 therapyHuman papillomavirus-associated headAnti-PD-1 blockadeNeck squamous cell carcinomaAdaptive immune resistanceAnti-PD1 monotherapyHPV(-) HNSCC patientsImmunogenic viral antigensImmune checkpoint moleculesPost-treatment biopsiesT cell activityImmune checkpoint pathwaysSquamous cell carcinomaQuantitative PCRImproved response ratesImmune-related genesCheckpoint moleculesPD-1IDO1 expression
2016
Antitumor Activity of Pembrolizumab in Biomarker-Unselected Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results From the Phase Ib KEYNOTE-012 Expansion Cohort
Chow LQM, Haddad R, Gupta S, Mahipal A, Mehra R, Tahara M, Berger R, Eder JP, Burtness B, Lee SH, Keam B, Kang H, Muro K, Weiss J, Geva R, Lin CC, Chung HC, Meister A, Dolled-Filhart M, Pathiraja K, Cheng JD, Seiwert TY. Antitumor Activity of Pembrolizumab in Biomarker-Unselected Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results From the Phase Ib KEYNOTE-012 Expansion Cohort. Journal Of Clinical Oncology 2016, 34: 3838-3845. PMID: 27646946, PMCID: PMC6804896, DOI: 10.1200/jco.2016.68.1478.Peer-Reviewed Original ResearchConceptsOverall response rateNeck squamous cell carcinomaProgression-free survivalSquamous cell carcinomaMetastatic headExpansion cohortPD-L1Cell carcinomaAnti-programmed death-1 antibodySix-month progression-free survivalTreatment-related adverse eventsEnd pointDeath-1 antibodyDose of pembrolizumabAntitumor activityPrimary end pointSecondary end pointsHuman papillomavirus (HPV) statusPD-L1 expressionOverall survival rateDurable antitumor activityFrequent dosing scheduleAssociation of responseAdvanced HNSCCM HNSCCSafety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial
Seiwert TY, Burtness B, Mehra R, Weiss J, Berger R, Eder JP, Heath K, McClanahan T, Lunceford J, Gause C, Cheng JD, Chow LQ. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. The Lancet Oncology 2016, 17: 956-965. PMID: 27247226, DOI: 10.1016/s1470-2045(16)30066-3.Peer-Reviewed Original ResearchConceptsMetastatic squamous cell carcinomaSquamous cell carcinomaDrug-related adverse eventsPost-baseline scanPhase 1b trialProportion of patientsCell carcinomaAdverse eventsPD-L1Anti-programmed death receptor 1 antibodyDeath receptor-1 (PD-1) antibodiesPositive squamous cell carcinomaActivity of pembrolizumabDose of pembrolizumabDrug-related rashMeaningful antitumour activityFull analysis setHPV-negative patientsSerious adverse eventsHPV-positive patientsPD-L1 expressionResponse Evaluation CriteriaTreatment of recurrentOverall responseDrug-related deathsPembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial
Muro K, Chung HC, Shankaran V, Geva R, Catenacci D, Gupta S, Eder JP, Golan T, Le DT, Burtness B, McRee AJ, Lin CC, Pathiraja K, Lunceford J, Emancipator K, Juco J, Koshiji M, Bang YJ. Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial. The Lancet Oncology 2016, 17: 717-726. PMID: 27157491, DOI: 10.1016/s1470-2045(16)00175-3.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsPost-baseline scanPhase 1b trialGastro-oesophageal junctionPD-L1Gastric cancerAdverse eventsMetastatic adenocarcinomaGrade 3 peripheral sensory neuropathyPositive advanced gastric cancerSolid Tumors version 1.1Anti-PD-1 antibodyDose of pembrolizumabGrade 3 fatigueGrade 4 pneumonitisMetastatic PD-L1Treatment-related deathsUnacceptable toxic effectsManageable toxicity profilePeripheral sensory neuropathyProportion of patientsResponse Evaluation CriteriaAdvanced gastric cancerPopulation of patientsClinical disease progression
2015
Antitumor activity and safety of pembrolizumab in patients (pts) with advanced squamous cell carcinoma of the head and neck (SCCHN): Preliminary results from KEYNOTE-012 expansion cohort.
Seiwert T, Haddad R, Gupta S, Mehra R, Tahara M, Berger R, Lee S, Burtness B, Le D, Heath K, Blum A, Dolled-Filhart M, Emancipator K, Pathiraja K, Cheng J, Chow L. Antitumor activity and safety of pembrolizumab in patients (pts) with advanced squamous cell carcinoma of the head and neck (SCCHN): Preliminary results from KEYNOTE-012 expansion cohort. Journal Of Clinical Oncology 2015, 33: lba6008-lba6008. DOI: 10.1200/jco.2015.33.18_suppl.lba6008.Peer-Reviewed Original ResearchRecurrent/metastatic SCCHNOverall response rateDrug-related adverse eventsProgression-free survivalAdverse eventsMetastatic SCCHNPD-L1KEYNOTE-012Expansion cohortOverall survivalCommon drug-related adverse eventsTumor-specific effector T cellsResponse rateAdvanced squamous cell carcinomaDrug-related gradePost-baseline scanSafety of pembrolizumabPrimary end pointLines of therapyPD-L1 expressionEffector T cellsSquamous cell carcinomaHumanized monoclonal antibodyPreliminary efficacy analysisAdvanced SCCHNInflamed-phenotype gene expression signatures to predict benefit from the anti-PD-1 antibody pembrolizumab in PD-L1+ head and neck cancer patients.
Seiwert T, Burtness B, Weiss J, Eder J, Yearley J, Murphy E, Nebozhyn M, McClanahan T, Ayers M, Lunceford J, Mehra R, Heath K, Cheng J, Chow L. Inflamed-phenotype gene expression signatures to predict benefit from the anti-PD-1 antibody pembrolizumab in PD-L1+ head and neck cancer patients. Journal Of Clinical Oncology 2015, 33: 6017-6017. DOI: 10.1200/jco.2015.33.15_suppl.6017.Peer-Reviewed Original Research