2023
Digital spatial profiling links beta-2-microglobulin expression with immune checkpoint blockade outcomes in head and neck squamous cell carcinoma
Gavrielatou N, Vathiotis I, Aung T, Shafi S, Burela S, Fernandez A, Moutafi M, Burtness B, Economopoulou P, Anastasiou M, Foukas P, Psyrri A, Rimm D. Digital spatial profiling links beta-2-microglobulin expression with immune checkpoint blockade outcomes in head and neck squamous cell carcinoma. Cancer Research Communications 2023, 3: 558-563. PMID: 37057033, PMCID: PMC10088911, DOI: 10.1158/2767-9764.crc-22-0299.Peer-Reviewed Original ResearchConceptsDigital spatial profilingB2M expressionOverall survivalM HNSCCImmunotherapy outcomesNeck squamous cell carcinoma (HNSCC) treatmentHigh beta-2 microglobulinSquamous cell carcinoma treatmentCell death protein 1Neck squamous cell carcinomaM expressionPretreatment biopsy samplesImmune checkpoint inhibitorsPD-L1 expressionImmune checkpoint markersDeath protein 1Squamous cell carcinomaB2MBeta-2-microglobulinBeta 2 microglobulin expressionImproved PFSCheckpoint inhibitorsMetastatic headCheckpoint markersImproved survival
2022
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).
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 inhibitorsA 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 evaluationPhase 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 treatmentsPhase 2 LEAP-009: Lenvatinib (Lenva) With or Without Pembrolizumab (Pembro) vs. Chemotherapy (Chemo) for Recurrent or Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC) That has Progressed on Platinum and Immunotherapy
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. Phase 2 LEAP-009: Lenvatinib (Lenva) With or Without Pembrolizumab (Pembro) vs. Chemotherapy (Chemo) for Recurrent or Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC) That has Progressed on Platinum and Immunotherapy. International Journal Of Radiation Oncology • Biology • Physics 2022, 112: e43-e44. DOI: 10.1016/j.ijrobp.2021.12.101.Peer-Reviewed Original ResearchPD-1/PD-L1 inhibitorsECOG performance statusPD-L1 inhibitorsM HNSCCDisease progressionRECIST v1.1Monotherapy armPerformance statusPO QDPD-L1 tumor proportion scoreOptimal second-line regimenEnd pointNeck squamous cell carcinomaPrimary end pointSecond-line regimenSecondary end pointsFirst-line treatmentTumor proportion scoreKey eligibility criteriaSquamous cell carcinomaInterim futility analysisMeasurable diseaseSOC chemotherapyMetastatic headUnacceptable toxicity
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 tumorsKEYNOTE-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 outcomesPembrolizumab (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 ratioPhase 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 survivalRandomized, 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 monotherapy
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 advancesProtocol-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
2017
Biomarkers predict enhanced clinical outcomes with afatinib versus methotrexate in patients with second-line recurrent and/or metastatic head and neck cancer
Cohen EEW, Licitra LF, Burtness B, Fayette J, Gauler T, Clement PM, Grau JJ, del Campo JM, Mailliez A, Haddad RI, Vermorken JB, Tahara M, Guigay J, Geoffrois L, Merlano MC, Dupuis N, Krämer N, Cong XJ, Gibson N, Solca F, Ehrnrooth E, Machiels J. Biomarkers predict enhanced clinical outcomes with afatinib versus methotrexate in patients with second-line recurrent and/or metastatic head and neck cancer. Annals Of Oncology 2017, 28: 2526-2532. PMID: 28961833, PMCID: PMC5834024, DOI: 10.1093/annonc/mdx344.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, IntravenousAdministration, OralAfatinibAntimetabolites, AntineoplasticBiomarkers, TumorBiopsyCarcinoma, Squamous CellDisease-Free SurvivalHead and Neck NeoplasmsHumansMethotrexateNeoplasm MetastasisNeoplasm Recurrence, LocalPredictive Value of TestsQuinazolinesSquamous Cell Carcinoma of Head and NeckConceptsProgression-free survivalMetastatic headEfficacy outcomesMedian progression-free survivalRecurrent/metastatic headNeck squamous cell carcinomaTumor biomarkersNeck 1 trialP16-positive diseaseSecond-line afatinibOverall study populationSubset of patientsP16-negative tumorsSquamous cell carcinomaEnhanced clinical outcomesBiomarker analysisM HNSCCTherapy-naïveBaseline characteristicsStudy entryClinical outcomesHNSCC patientsPlatinum therapyCell carcinomaNeck cancerPTEN loss as a predictive biomarker in head and neck squamous cell cancer (HNSCC) patients treated with cetuximab (C).
Eze N, Chung C, Neumeister V, Sandoval-Schaefer T, Lee J, Burtness B. PTEN loss as a predictive biomarker in head and neck squamous cell cancer (HNSCC) patients treated with cetuximab (C). Journal Of Clinical Oncology 2017, 35: e17520-e17520. DOI: 10.1200/jco.2017.35.15_suppl.e17520.Peer-Reviewed Original ResearchM HNSCCHazard ratioPTEN lossPTEN analysisLow tumorsExact testHigh tumorNeck squamous cell cancer patientsSquamous cell cancer patientsCox proportional hazards modelWild-type patientsHigh expression groupProportional hazards modelFisher's exact testPTEN testingC therapyFirst tertilePatient selectionKaplan-MeierType patientsCancer patientsPredictive biomarkersPIK3CA mutationsExpression groupHazards model
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 HNSCC
2013
Association of the 3'-untranslated region KRAS-variant with cisplatin resistance in patients with recurrent and/or metastatic head and neck squamous cell carcinoma.
Weidhaas J, Lee J, Slebos R, Howard J, Perez J, Gilbert J, Nallur S, Paranjape T, Garcia J, Burtness B, Forastiere A, Chung C. Association of the 3'-untranslated region KRAS-variant with cisplatin resistance in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Journal Of Clinical Oncology 2013, 31: 6016-6016. DOI: 10.1200/jco.2013.31.15_suppl.6016.Peer-Reviewed Original ResearchNeck squamous cell carcinomaSquamous cell carcinomaKRAS-variantMetastatic headCell carcinomaP16/HPV statusRecurrent/metastatic headPoor progression-free survivalCisplatin resistanceHuman papillomavirus (HPV) statusProgression-free survivalTG/GGM HNSCCTumor DNA samplesHPV statusPatient demographicsHNSCC patientsClinical outcomesPoor outcomePoor prognosisPrognostic significancePredictive biomarkersClinical trialsProspective validationPromising biomarker