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, Figueiredo Lima I, Oppelt P, da Cunha Junior 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, jco2302625. PMID: 39038265, 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-L1A Phase 1 Dose-escalation and Expansion Study of CUE-101, Given As Monotherapy in 3rd Line and in Combination with Pembrolizumab in 1st Line Recurrent/Metastatic (R/M) HPV16+ Head and Neck Cancer Patients
Colevas A, Chung C, Adkins D, Rodriguez C, Park J, Gibson M, Sukari A, Burtness B, Johnson F, Julian R, Saba N, Worden F, Dunn L, Seiwert T, Jotte R, Haddad R, Gabrail N, Bauman J, Margossian S, Pai S. A Phase 1 Dose-escalation and Expansion Study of CUE-101, Given As Monotherapy in 3rd Line and in Combination with Pembrolizumab in 1st Line Recurrent/Metastatic (R/M) HPV16+ Head and Neck Cancer Patients. International Journal Of Radiation Oncology • Biology • Physics 2024, 118: e87. DOI: 10.1016/j.ijrobp.2024.01.192.Peer-Reviewed Original ResearchCD8+ T cellsR/M HNSCCHuman leukocyte antigenT cellsHLA-A*0201Phase 1 dose-escalationTumor antigen-specific CD8First-in-human studyHead and neck cancer patientsTargeted delivery of cytokinesHLA-A*0201 patientsHPV16 E7 peptidesRecurrent/metastatic (R/MData cut-offInfusion-related reactionsT-cell engagersDelivery of cytokinesNeck cancer patientsTreatment of patientsPembrolizumab combinationDose escalationEscalating dosesComplete responseMaculopapular rashLeukocyte antigen
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 inhibitors
2017
LUX-head and neck 2: Randomized, double-blind, placebo-controlled, phase III trial of afatinib as adjuvant therapy after chemoradiation (CRT) in primary unresected, high/intermediate-risk, squamous cell cancer of the head and neck (HNSCC) patients (pts).
Burtness B, Haddad R, Dinis J, Trigo Perez J, Yokota T, Viana L, Romanov I, Vermorken J, Bourhis J, Tahara M, Segalla J, Psyrri A, Vasilevskaya I, Nangia C, Chaves-Conde M, Wang B, Gibson N, Ehrnrooth E, Harrington K, Cohen E. LUX-head and neck 2: Randomized, double-blind, placebo-controlled, phase III trial of afatinib as adjuvant therapy after chemoradiation (CRT) in primary unresected, high/intermediate-risk, squamous cell cancer of the head and neck (HNSCC) patients (pts). Journal Of Clinical Oncology 2017, 35: 6001-6001. DOI: 10.1200/jco.2017.35.15_suppl.6001.Peer-Reviewed Original ResearchDisease-free survivalPhase III trialsIII trialsEGFR inhibitionMedian disease-free survivalRecurrent/metastatic diseaseErbB family blocker afatinibPre-planned interim analysisECOG PS 0Median treatment durationSquamous cell cancerDefinitive chemoradiationECOG PSEligible ptsAdvanced HNSCCConcurrent cisplatinN2 diseasePrimary endpointAdjuvant therapyMetastatic diseasePS 0Complete responseDisease recurrenceMedian ageNodal stage
2014
LBA31 A Phase Ib Study of Pembrolizumab (Pembro; Mk-3475) in Patients (Pts) with Human Papiilloma Virus (Hpv)-Positive and Negative Head and Neck Cancer (Hnc)
Chow L, Burtness B, Weiss J, Berger R, Eder J, Gonzalez E, Pulini J, Johnson J, Dolled-Filhart M, Emancipator K, Lunceford J, Pathiraja K, Gause C, Cheng J, Seiwert T. LBA31 A Phase Ib Study of Pembrolizumab (Pembro; Mk-3475) in Patients (Pts) with Human Papiilloma Virus (Hpv)-Positive and Negative Head and Neck Cancer (Hnc). Annals Of Oncology 2014, 25: v1. DOI: 10.1093/annonc/mdu438.32.Peer-Reviewed Original ResearchOverall response ratePD-L1 expressionDrug-related adverse eventsAdverse eventsRECIST v1.1Subsidiary of MerckBristol-Myers SquibbInvestigator reviewAntitumor activityCommon drug-related adverse eventsAdvisory board membershipHigh PD-L1 expressionBoehringer IngelheimMerck SharpGenentech/RochePhase Ib studyPrimary end pointDrug-related deathsMeasurable diseaseMedian OSMedian PFSMetastatic HNCAdvanced HNCUnacceptable toxicityComplete responseInduction cetuximab, paclitaxel, and carboplatin followed by chemoradiation with cetuximab, paclitaxel, and carboplatin for stage III/IV head and neck squamous cancer: a phase II ECOG-ACRIN trial (E2303)
Wanebo HJ, Lee J, Burtness BA, Ridge JA, Ghebremichael M, Spencer SA, Psyrri D, Pectasides E, Rimm D, Rosen FR, Hancock MR, Tolba KA, Forastiere AA. Induction cetuximab, paclitaxel, and carboplatin followed by chemoradiation with cetuximab, paclitaxel, and carboplatin for stage III/IV head and neck squamous cancer: a phase II ECOG-ACRIN trial (E2303). Annals Of Oncology 2014, 25: 2036-2041. PMID: 25009013, PMCID: PMC4176450, DOI: 10.1093/annonc/mdu248.Peer-Reviewed Original ResearchConceptsEvent-free survivalStage III/IV headResponse/survivalInduction therapyComplete responseStage III/IV HNSCCNeck squamous cell carcinomaPrimary site biopsiesTreatment-related deathsPathologic complete responseNeck squamous cancerSquamous cell carcinomaProtein expression statusEligible patientsSite biopsiesOverall survivalCell carcinomaPromising survivalSquamous cancerDisease progressionChemoradiationRadiation therapyPatientsWeek 9CetuximabE1308: Reduced-dose IMRT in human papilloma virus (HPV)-associated resectable oropharyngeal squamous carcinomas (OPSCC) after clinical complete response (cCR) to induction chemotherapy (IC).
Cmelak A, Li S, Marur S, Zhao W, Westra W, Chung C, Gillison M, Gilbert J, Bauman J, Wagner L, Ferris R, Trevarthen D, Colevas A, Jahagirdar B, Burtness B. E1308: Reduced-dose IMRT in human papilloma virus (HPV)-associated resectable oropharyngeal squamous carcinomas (OPSCC) after clinical complete response (cCR) to induction chemotherapy (IC). Journal Of Clinical Oncology 2014, 32: lba6006-lba6006. DOI: 10.1200/jco.2014.32.18_suppl.lba6006.Peer-Reviewed Original ResearchClinical complete responseOropharyngeal squamous carcinomaLate grade 3 toxicityPost-treatment neck dissectionStage III/IVAHigh tumor control ratesGrade 3 toxicityWeek x 3Tumor control rateHuman papilloma virusLate toxicityPrimary endpointCurrent smokersComplete responseNeck dissectionNodal stageSquamous carcinomaControl ratePapilloma virusC-IMRTT1-3Weekly schedulePFSInvolved nodesDoseE1308: Reduced-dose IMRT in human papilloma virus (HPV)-associated resectable oropharyngeal squamous carcinomas (OPSCC) after clinical complete response (cCR) to induction chemotherapy (IC).
Cmelak A, Li S, Marur S, Zhao W, Westra W, Chung C, Gillison M, Gilbert J, Bauman J, Wagner L, Ferris R, Trevarthen D, Colevas A, Jahagirdar B, Burtness B. E1308: Reduced-dose IMRT in human papilloma virus (HPV)-associated resectable oropharyngeal squamous carcinomas (OPSCC) after clinical complete response (cCR) to induction chemotherapy (IC). Journal Of Clinical Oncology 2014, 32: lba6006-lba6006. DOI: 10.1200/jco.2014.32.15_suppl.lba6006.Peer-Reviewed Original Research
2012
A phase I evaluation of vandetanib plus paclitaxel, carboplatin, 5-fluorouracil, and XRT induction therapy followed by surgery for previously untreated locally advanced cancer of the esophagus and GE junction.
Astsaturov I, Meyer J, Cheng J, Olszanski A, Dushkin H, Berger A, Davey M, Cohen S, Burtness B, Scott W. A phase I evaluation of vandetanib plus paclitaxel, carboplatin, 5-fluorouracil, and XRT induction therapy followed by surgery for previously untreated locally advanced cancer of the esophagus and GE junction. Journal Of Clinical Oncology 2012, 30: 74-74. DOI: 10.1200/jco.2012.30.4_suppl.74.Peer-Reviewed Original ResearchSquamous carcinomaGrade 3 non-hematological toxicityOpen-label phase IOperable esophagealFox Chase Cancer CenterNon-hematological toxicitiesPathologic complete responsePhase I evaluationAST/ALTPromising clinical activityEsophageal squamous carcinomaPET/CTCarboplatin AUC5Male ptsAbdominal painCurative intentGI hemorrhageInduction chemoradiotherapyInduction therapyDistant recurrenceInduction chemoradiationMedian followupComplete responseAdvanced cancerDose escalationEffect of increased time from chemoradiation to surgery on the pathologic complete response rate in patients with esophageal cancer.
Shaikh T, Ruth K, Scott W, Burtness B, Cohen S, Konski A, Cooper H, Astsaturov I, Meyer J. Effect of increased time from chemoradiation to surgery on the pathologic complete response rate in patients with esophageal cancer. Journal Of Clinical Oncology 2012, 30: 84-84. DOI: 10.1200/jco.2012.30.4_suppl.84.Peer-Reviewed Original ResearchPathologic complete responseEsophageal cancerPathologic complete response rateT3/T4 lesionsT1/T2 lesionsCarboplatin-based therapyTri-modality treatmentComplete response rateMedian radiation doseType of chemotherapyResectable esophageal cancerMultivariable logistic regressionSquamous cell carcinomaRadiation doseEnd of chemoradiationTrimodality therapyDistant recurrenceSubsequent surgeryT4 lesionsComplete responseMedian ageRectal cancerT2 lesionsMedian timeMultivariable analysis
2009
Phase II trial of docetaxel–irinotecan combination in advanced esophageal cancer
Burtness B, Gibson M, Egleston B, Mehra R, Thomas L, Sipples R, Quintanilla M, Lacy J, Watkins S, Murren JR, Forastiere AA. Phase II trial of docetaxel–irinotecan combination in advanced esophageal cancer. Annals Of Oncology 2009, 20: 1242-1248. PMID: 19429872, PMCID: PMC2699385, DOI: 10.1093/annonc/mdn787.Peer-Reviewed Original ResearchConceptsAdvanced esophageal cancerPartial responseComplete responseEligible patientsEsophageal cancerEastern Cooperative Oncology Group performance statusMetastatic squamous cell carcinomaSafety of docetaxelPhase II trialSquamous cell carcinomaPrincipal toxic effectsAssessable patientsEsophagogastric cancerMeasurable diseaseToxic deathsII trialCN patientsMedian survivalPerformance statusNormal bilirubinPreclinical evidenceMedian timeCell carcinomaMyocardial infarctionTumor assessment
2007
Phase II Trial of Weekly Docetaxel/Irinotecan Combination in Advanced Pancreatic Cancer
Burtness B, Thomas L, Sipples R, McGurk M, Salikooti S, Christoforou M, Mirto G, Salem R, Sosa J, Kloss R, Rahman Z, Chung G, Lacy J, Murren JR. Phase II Trial of Weekly Docetaxel/Irinotecan Combination in Advanced Pancreatic Cancer. The Cancer Journal 2007, 13: 257-262. PMID: 17762761, DOI: 10.1097/ppo.0b013e31813c1174.Peer-Reviewed Original ResearchConceptsAdvanced pancreatic cancerPancreatic cancerEligible patientsIrinotecan combinationPartial responseComplete responseEastern Cooperative Oncology Group performance status 0Principal grade 3/4 toxicitiesWorld Health Organization criteriaSafety of docetaxelGrade 3/4 toxicitiesObjective response ratePerformance status 0One-year survivalPhase II trialCombination of docetaxelNormal bilirubin levelsEvaluable patientsFebrile neutropeniaMeasurable diseaseStatus 0Toxic deathsUnresectable diseaseII trialRecurrent disease
2006
Hepatic metastasectomy following FOLFOX therapy in patients with colorectal metastases
Arciero C, Salem R, Lacy J, Sigurdson E, Hoffman J, Watson J, Joseph N, Cooper H, Meropol N, Burtness B. Hepatic metastasectomy following FOLFOX therapy in patients with colorectal metastases. Journal Of Clinical Oncology 2006, 24: 13523-13523. DOI: 10.1200/jco.2006.24.18_suppl.13523.Peer-Reviewed Original ResearchHepatic metastasectomyPathologic complete responseFOLFOX chemotherapySynchronous metastasesAdverse prognostic featuresHigher lesion numberMedian age 55Multiple wedge resectionsTumor size 1Portal lymph nodesMetastatic colon cancerResidual cancer cellsCurative intentMedian followColorectal metastasesFOLFOX therapyOverall survivalOxaliplatin chemotherapyPathologic responseRadiographic responseResidual cancerSystemic therapyWedge resectionComplete resectionComplete responsePostchemotherapy MRI Overestimates Residual Disease Compared with Histopathology in Responders to Neoadjuvant Therapy for Locally Advanced Breast Cancer
Kwong MS, Chung GG, Horvath LJ, Ward BA, Hsu AD, Carter D, Tavassoli F, Haffty B, Burtness BA. Postchemotherapy MRI Overestimates Residual Disease Compared with Histopathology in Responders to Neoadjuvant Therapy for Locally Advanced Breast Cancer. The Cancer Journal 2006, 12: 212-221. PMID: 16803680, DOI: 10.1097/00130404-200605000-00010.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantDocetaxelDoxorubicinFemaleGranulocyte Colony-Stimulating FactorHumansMagnetic Resonance ImagingMastectomyMiddle AgedNeoadjuvant TherapyNeoplasm InvasivenessNeoplasm, ResidualPrognosisSurvival RateTaxoidsTreatment OutcomeConceptsAdvanced breast cancerPathologic complete responseMagnetic resonance imagingComplete responseBreast cancerResonance imagingNeoadjuvant chemotherapyPreoperative magnetic resonance imagingResidual invasive carcinomaBreast magnetic resonance imagingResidual tumor sizeSerial magnetic resonanceBreast magnetic resonanceMagnetic resonanceEligible patientsPrimary chemotherapyNeoadjuvant therapyResidual cancerAxillary lesionsPathologic evaluationStable patientsAdditional patientsPosttreatment examinationResidual diseaseTumor size
2003
Epidermal growth factor receptor, p53 mutation, and pathological response predict survival in patients with locally advanced esophageal cancer treated with preoperative chemoradiotherapy.
Gibson MK, Abraham SC, Wu TT, Burtness B, Heitmiller RF, Heath E, Forastiere A. Epidermal growth factor receptor, p53 mutation, and pathological response predict survival in patients with locally advanced esophageal cancer treated with preoperative chemoradiotherapy. Clinical Cancer Research 2003, 9: 6461-8. PMID: 14695149.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAgedBcl-2-Associated X ProteinCisplatinCombined Modality TherapyDisease-Free SurvivalDNA Mutational AnalysisErbB ReceptorsEsophageal NeoplasmsFemaleFluorouracilGenes, p53HumansImmunohistochemistryMaleMiddle AgedMutationProportional Hazards ModelsProto-Oncogene ProteinsProto-Oncogene Proteins c-bcl-2Regression AnalysisTime FactorsTreatment OutcomeConceptsAdvanced esophageal cancerOverall survivalComplete responseEsophageal cancerEpidermal growth factor receptorP53 mutationsGrowth factor receptorClinical covariatesCellular markersBetter tumor differentiationPathological complete responseFactor receptorEGF-R expressionBcl-2 expressionInfusional cisplatinDaily radiotherapyMost patientsPoor OSPreoperative chemoradiotherapyPatient agePretreatment tumorOutcome predictorsPredictive factorsBarrett's metaplasiaTumor locationMature survival results with preoperative cisplatin, protracted infusion 5-fluorouracil, and 44-Gy radiotherapy for esophageal cancer
Kleinberg L, Knisely JP, Heitmiller R, Zahurak M, Salem R, Burtness B, Heath EI, Forastiere AA. Mature survival results with preoperative cisplatin, protracted infusion 5-fluorouracil, and 44-Gy radiotherapy for esophageal cancer. International Journal Of Radiation Oncology • Biology • Physics 2003, 56: 328-334. PMID: 12738305, DOI: 10.1016/s0360-3016(02)04598-4.Peer-Reviewed Original ResearchConceptsTime of surgeryEsophageal cancerDay 1Survival rateNeoadjuvant therapyPreoperative therapyMedian survivalComplete responseVenous infusionSurvival resultsResponse rateDisease-specific survival ratesLong-term survival resultsPathologic complete response rateCycles of paclitaxelPathologic stage IIAComplete response ratePathologic complete responsePathologic stage IRemainder of patientsDisease-specific survivalOverall cure rateSquamous cell carcinomaIsolated local failureCancer-related death
2000
Phase II evaluation of preoperative chemoradiation and postoperative adjuvant chemotherapy for squamous cell and adenocarcinoma of the esophagus.
Heath E, Burtness B, Heitmiller R, Salem R, Kleinberg L, Knisely J, Yang S, Talamini M, Kaufman H, Canto M, Topazian M, Wu T, Olukayode K, Forastiere A. Phase II evaluation of preoperative chemoradiation and postoperative adjuvant chemotherapy for squamous cell and adenocarcinoma of the esophagus. Journal Of Clinical Oncology 2000, 18: 868-76. PMID: 10673530, DOI: 10.1200/jco.2000.18.4.868.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAntimetabolites, AntineoplasticAntineoplastic AgentsAntineoplastic Agents, PhytogenicAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Squamous CellChemotherapy, AdjuvantCisplatinEsophageal NeoplasmsEsophagectomyFeasibility StudiesFemaleFluorouracilFollow-Up StudiesHumansMaleMiddle AgedNeoadjuvant TherapyNeoplasm StagingPaclitaxelRadiotherapy DosageRemission InductionSurvival RateTreatment OutcomeConceptsSurvival rateAdjuvant chemotherapyPreoperative chemoradiationComplete responseComplete pathologic response rateCompletion of chemoradiotherapyContinuous infusion cisplatinPathologic response ratePostoperative adjuvant chemotherapyPostoperative adjuvant therapyPathologic complete responsePhase II trialPhase II evaluationComplete tumor resectionContinuous intravenous infusionMedian survival timePathologic complete respondersExcellent survival ratesGy of radiationPatterns of failurePreoperative treatment planPreoperative cisplatinComplete respondersPreoperative treatmentResectable cancer