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-L1Correlative and spatial biomarker analysis of a phase 1/2b study to evaluate pepinemab in combination with pembrolizumab for first-line treatment of patients with recurrent or metastatic head and neck cancer.
Evans E, Fisher T, Mallow C, Foster A, Leonard J, Chaney M, Mekhail T, Seetharamu N, Steuer C, Saba N, Adkins D, Beck J, Algazi A, Burtness B, Baumgart M, Giampoli E, Hager S, Chay C, Spira A, Zauderer M. Correlative and spatial biomarker analysis of a phase 1/2b study to evaluate pepinemab in combination with pembrolizumab for first-line treatment of patients with recurrent or metastatic head and neck cancer. Journal Of Clinical Oncology 2024, 42: 2603-2603. DOI: 10.1200/jco.2024.42.16_suppl.2603.Peer-Reviewed Original ResearchHead and neck squamous cell carcinomaMyeloid suppressor cellsImmune checkpoint inhibitorsFirst-line treatmentDendritic cellsT cellsB cellsTumor biopsiesLymphoid structuresImmune cellsMetastatic head and neck squamous cell carcinomaActivity of immune checkpoint inhibitorsEfficacy of immune checkpoint inhibitorsSingle-arm open-label studyFirst-line treatment of patientsMetastatic head and neck cancerHead and neck squamous cell carcinoma tumorsImmune checkpoint inhibitor activationOn-treatment tumor biopsiesSuppression of adaptive immunityCD8+ T cellsNeck squamous cell carcinomaHead and neck cancerAnalysis of tumor biopsiesMechanism of immune enhancementLenvatinib ± Pembrolizumab Versus Chemotherapy for Recurrent/Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC) That Progressed after Platinum and Immunotherapy: The Phase 2 LEAP-009 Study
Harrington K, Kim H, Salas S, Oliva M, Metcalf R, Bernsdorf M, Kim J, Cohen E, Siu L, Rischin D, Licitra L, Vermorken J, Le Q, Tahara M, Machiels J, O'Hara K, Pathiraja K, Gumuscu B, Bidadi B, Burtness B. Lenvatinib ± Pembrolizumab Versus Chemotherapy for Recurrent/Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC) That Progressed after Platinum and Immunotherapy: The Phase 2 LEAP-009 Study. International Journal Of Radiation Oncology • Biology • Physics 2024, 118: e42. DOI: 10.1016/j.ijrobp.2024.01.095.Peer-Reviewed Original ResearchR/M HNSCCHead and neck squamous cell carcinomaPD-1/L1 inhibitorsPlatinum-based therapyPlatinum-based chemotherapyDisease progressionLenvatinib monotherapyECOG PSRecurrent/metastatic (R/M) head and neck squamous cell carcinomaPD-L1 tumor proportion scoreStandard-of-care chemotherapyNeck squamous cell carcinomaTumor proportion scoreProgression-free survivalDuration of responseEfficacy of lenvatinibSecondary end pointsFirst-line treatmentSquamous cell carcinomaEfficacious treatment optionStandard of careOral lenvatinibPembrolizumab monotherapyRECIST v1.1Monotherapy arm
2023
Top advances of the year: Head and neck cancer
Verma A, Burtness B. Top advances of the year: Head and neck cancer. Cancer 2023, 129: 1308-1312. PMID: 36692372, DOI: 10.1002/cncr.34654.Peer-Reviewed Original ResearchConceptsProgression-free survivalFavorable-risk patientsRisk patientsNeck cancerHuman papillomavirus-associated oropharyngeal cancerGemcitabine/cisplatin chemotherapyImmature survival dataVirus-related cancersIntermediate-risk patientsFirst-line treatmentPhase 3 trialCooperative group trialsTreatment deintensificationMetastatic headOverall survivalPostoperative therapySmoking historyOropharyngeal cancerAntibody nivolumabCisplatin chemotherapyTransoral resectionTransoral surgeryNasopharyngeal cancerGroup trialsGy radiationTreating Head and Neck Cancer in the Age of Immunotherapy: A 2023 Update
Bhatia A, Burtness B. Treating Head and Neck Cancer in the Age of Immunotherapy: A 2023 Update. Drugs 2023, 83: 217-248. PMID: 36645621, DOI: 10.1007/s40265-023-01835-2.Commentaries, Editorials and LettersConceptsNeck cancerRecurrent/metastatic settingImmune checkpoint inhibitor nivolumabNeck squamous cell carcinomaAge of immunotherapyLate stage HNSCCImmune checkpoint inhibitionPlatinum-containing chemotherapyFirst-line treatmentGrowth factor receptor overexpressionCheckpoint inhibitor nivolumabSquamous cell carcinomaEpidermal growth factor receptor (EGFR) overexpressionPathogenesis of HNSCCTreatment of patientsTreatment of HNSCCManagement of headMonoclonal antibody cetuximabCurative intentPalliative chemotherapyAdvanced diseaseInhibitor nivolumabLocoregional failureMetastatic settingMultimodality therapy
2022
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
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 new prognostic model in patients with recurrent or metastatic head and neck cancer treated with chemotherapy: An analysis of ECOG-ACRIN E1305.
Argiris A, Flamand Y, Savvides P, Johnson J, Li S, Forastiere A, Burtness B. A new prognostic model in patients with recurrent or metastatic head and neck cancer treated with chemotherapy: An analysis of ECOG-ACRIN E1305. Journal Of Clinical Oncology 2022, 40: 6026-6026. DOI: 10.1200/jco.2022.40.16_suppl.6026.Peer-Reviewed Original ResearchOverall survivalFirst-line treatmentMedian OSPrognostic factorsHazard ratioBone/liver metastasesRM-SCCHNFirst-lineFirst-line treatment of patientsMultivariate modelMetastatic squamous cell carcinomaPhase III randomized trialRisk factorsCancer treated with chemotherapyPlatinum-based chemotherapyECOG performance statusCooperative group trialsSquamous cell carcinomaHead and neckTumor cell differentiationTreatment of patientsPrognostic scoring modelCox proportional hazards modelsProportional hazards modelPrior radiationA phase 1 dose-escalation and expansion study of CUE-101, a novel HPV16 E7-pHLA-IL2-Fc fusion protein, given alone and in combination with pembrolizumab in patients with recurrent/metastatic HPV16+ head and neck cancer.
Chung C, Colevas A, Adkins D, Gibson M, Rodriguez C, Sukari A, Bauman J, Wirth L, Johnson F, Saba N, Burtness B, Dunn L, Seiwert T, Worden F, Muzaffar J, Margossian S, Moniz R, Quayle S, Levisetti M, Pai S. A phase 1 dose-escalation and expansion study of CUE-101, a novel HPV16 E7-pHLA-IL2-Fc fusion protein, given alone and in combination with pembrolizumab in patients with recurrent/metastatic HPV16+ head and neck cancer. Journal Of Clinical Oncology 2022, 40: 6045-6045. DOI: 10.1200/jco.2022.40.16_suppl.6045.Peer-Reviewed Original ResearchCD8+ T cellsHuman leukocyte antigenT cellsInterleukin-2R/M HNSCCHLA-A*0201Recurrent/metastatic head and neck squamous cell carcinomaTumor antigen-specific T cellsHead and neck squamous cell carcinomaDelivery of interleukin-2Phase 1 dose-escalationRecommended phase 2 doseTumor antigen-specific CD8Neck squamous cell carcinomaFirst-in-human studyAntitumor activityDose-escalation cohortsHLA-A*0201 patientsPhase 2 doseTumor-specific CD8Data cut-offSpecific T cellsFirst-line treatmentSquamous cell carcinomaDose-dependent increasePhase 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 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 pointSecondary end pointsSecond-line regimenFirst-line treatmentTumor proportion scoreKey eligibility criteriaSquamous cell carcinomaInterim futility analysisMeasurable diseaseSOC chemotherapyMetastatic headUnacceptable toxicity
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 carcinoma
2019
Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study
Burtness B, Harrington KJ, Greil R, Soulières D, Tahara M, de Castro G, Psyrri A, Basté N, Neupane P, Bratland Å, Fuereder T, Hughes BGM, Mesía R, Ngamphaiboon N, Rordorf T, Ishak W, Hong RL, Mendoza R, Roy A, Zhang Y, Gumuscu B, Cheng JD, Jin F, Rischin D, Investigators K, Lerzo G, Tatangelo M, Varela M, Zarba J, Boyer M, Gan H, Gao B, Hughes B, Mallesara G, Rischin D, Taylor A, Burian M, Fuereder T, Greil R, Barrios C, de Castro D, Castro G, Franke F, Girotto G, Lima I, Nicolau U, Pinto G, Santos L, Victorino A, Chua N, Couture F, Gregg R, Hansen A, Hilton J, McCarthy J, Soulieres D, Ascui R, Gonzalez P, Villanueva L, Torregroza M, Zambrano A, Holeckova P, Kral Z, Melichar B, Prausova J, Vosmik M, Andersen M, Gyldenkerne N, Jurgens H, Putnik K, Reinikainen P, Gruenwald V, Laban S, Aravantinos G, Boukovinas I, Georgoulias V, Psyrri A, Kwong D, Al-Farhat Y, Csoszi T, Erfan J, Horvai G, Landherr L, Remenar E, Ruzsa A, Szota J, Billan S, Gluck I, Gutfeld O, Popovtzer A, Benasso M, Bui S, Ferrari V, Licitra L, Nole F, Fujii T, Fujimoto Y, Hanai N, Hara H, Matsumoto K, Mitsugi K, Monden N, Nakayama M, Okami K, Oridate N, Shiga K, Shimizu Y, Sugasawa M, Tahara M, Takahashi M, Takahashi S, Tanaka K, Ueda T, Yamaguchi H, Yamazaki T, Yasumatsu R, Yokota T, Yoshizaki T, Kudaba I, Stara Z, Ishak W, Cheah S, Ponce J, Mendoza R, Hernandez C, Soto F, Buter J, Hoeben A, Oosting S, Suijkerbuijk K, Bratland A, Brydoey M, Alvarez R, Mas L, Caguioa P, Querol J, Regala E, Tamayo M, Villegas E, Kawecki A, Karpenko A, Klochikhin A, Smolin A, Zarubenkov O, Goh B, Cohen G, du Toit J, Jordaan C, Landers G, Ruff P, Szpak W, Tabane N, Brana I, Docampo L, Lavernia J, Mesia R, Abel E, Muratidu V, Nielsen N, Cristina V, Rordorf T, Rothschild S, Hong R, Wang H, Yang M, Yeh S, Yen C, Ngamphaiboon N, Soparattanapaisarn N, Sriuranpong V, Aksoy S, Cicin I, Ekenel M, Harputluoglu H, Ozyilkan O, Harrington K, Agarwala S, Ali H, Alter R, Anderson D, Bruce J, Burtness B, Campbell N, Conde M, Deeken J, Edenfield W, Feldman L, Gaughan E, Goueli B, Halmos B, Hegde U, Hunis B, Jotte R, Karnad A, Khan S, Laudi N, Laux D, Martincic D, McCune S, McGaughey D, Misiukiewicz K, Mulford D, Nadler E, Neupane P, Nunnink J, Ohr J, O'Malley M, Patson B, Paul D, Popa E, Powell S, Redman R, Rella V, Lima C, Sivapiragasam A, Su Y, Sukari A, Wong S, Yilmaz E, Yorio J. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. The Lancet 2019, 394: 1915-1928. PMID: 31679945, DOI: 10.1016/s0140-6736(19)32591-7.Peer-Reviewed Original ResearchConceptsCombined positive scoreSecond interim analysisProgression-free survivalPD-L1 combined positive scoreAppropriate first-line treatmentFirst-line treatmentOverall survivalSquamous cell carcinomaChemotherapy groupMetastatic HNSCCInterim analysisAdverse eventsAlone groupCell carcinomaFinal analysisCell death ligand 1 (PD-L1) expressionDeath ligand 1 (PD-L1) expressionMetastatic squamous cell carcinomaNeck squamous cell carcinomaCause adverse eventsPD-L1 positivityLigand 1 expressionPD-L1 expressionTotal populationIncurable recurrentThe Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC)
Cohen EEW, Bell RB, Bifulco CB, Burtness B, Gillison ML, Harrington KJ, Le QT, Lee NY, Leidner R, Lewis RL, Licitra L, Mehanna H, Mell LK, Raben A, Sikora AG, Uppaluri R, Whitworth F, Zandberg DP, Ferris RL. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC). Journal For ImmunoTherapy Of Cancer 2019, 7: 184. PMID: 31307547, PMCID: PMC6632213, DOI: 10.1186/s40425-019-0662-5.Peer-Reviewed Original ResearchConceptsSquamous cell carcinomaTreatment of patientsCell carcinomaNeck cancerAnti-PD-1 immune checkpoint inhibitorPD-L1 combined positive scoreMetastatic squamous cell carcinomaRecurrent squamous cell carcinomaApproval of nivolumabCancer consensus statementFirst new therapyImmune checkpoint inhibitorsPlatinum-based regimensPlatinum-containing chemotherapyRole of immunotherapyCombined positive scoreFirst-line treatmentPD-1 inhibitionTreatment of recurrentTumor proportion scoreAppropriate patient selectionAdverse event managementSame patient populationImmunotherapy of cancerCheckpoint inhibitors
2017
Phase III randomized trial of chemotherapy with or without bevacizumab (B) in patients (pts) with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): Survival analysis of E1305, an ECOG-ACRIN Cancer Research Group trial.
Argiris A, Li S, Savvides P, Ohr J, Gilbert J, Levine M, Haigentz M, Saba N, Chakravarti A, Ikpeazu C, Schneider C, Pinto H, Forastiere A, Burtness B. Phase III randomized trial of chemotherapy with or without bevacizumab (B) in patients (pts) with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): Survival analysis of E1305, an ECOG-ACRIN Cancer Research Group trial. Journal Of Clinical Oncology 2017, 35: 6000-6000. DOI: 10.1200/jco.2017.35.15_suppl.6000.Peer-Reviewed Original ResearchMedian overall survivalOverall survivalArm BM SCCHNAUC 6Hazard ratioArm AResponse rateMetastatic squamous cell carcinomaAnti-VEGF monoclonal antibodyCarboplatin AUC 6Objective response ratePerformance status 0Trial of chemotherapyFirst-line treatmentSquamous cell carcinomaImproved response ratesA vs BEligible ptsMedian PFSOropharyngeal primaryPlatinum doubletsStatus 0Primary endpointProphylactic antibiotics
2015
342TiP Phase 3 trial of pembrolizumab as a first-line treatment in subjects with recurrent/metastatic head and neck squamous cell carcinoma: KEYNOTE-048
Yen C, Klochikhin A, Cohen E, Vermorken J, Harrington K, Tahara M, Ge J, Geib J, Jin F, Burtness B. 342TiP Phase 3 trial of pembrolizumab as a first-line treatment in subjects with recurrent/metastatic head and neck squamous cell carcinoma: KEYNOTE-048. Annals Of Oncology 2015, 26: ix93. DOI: 10.1093/annonc/mdv527.29.Peer-Reviewed Original Research11TiP Phase 3 trial of pembrolizumab as a first-line treatment in subjects with recurrent/metastatic head and neck squamous cell carcinoma: KEYNOTE-048
Klochikhin A, Greil R, Cohen E, Vermorken J, Harrington K, Tahara M, Ge J, Geib J, Jin F, Burtness B. 11TiP Phase 3 trial of pembrolizumab as a first-line treatment in subjects with recurrent/metastatic head and neck squamous cell carcinoma: KEYNOTE-048. Annals Of Oncology 2015, 26: viii5. DOI: 10.1093/annonc/mdv514.01.Peer-Reviewed Original Research
2012
A Phase II Study of Capecitabine, Oxaliplatin, and Cetuximab with or Without Bevacizumab as Frontline Therapy for Metastatic Colorectal Cancer. A Fox Chase Extramural Research Study
Dotan E, Meropol NJ, Burtness B, Denlinger CS, Lee J, Mintzer D, Zhu F, Ruth K, Tuttle H, Sylvester J, Cohen SJ. A Phase II Study of Capecitabine, Oxaliplatin, and Cetuximab with or Without Bevacizumab as Frontline Therapy for Metastatic Colorectal Cancer. A Fox Chase Extramural Research Study. Journal Of Gastrointestinal Cancer 2012, 43: 562-569. PMID: 22294255, PMCID: PMC3400721, DOI: 10.1007/s12029-012-9368-3.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factorMetastatic colorectal cancerPhase II studyEpidermal growth factor receptorDay 1Arm B.II studyOverall survivalArm AColorectal cancerResponse rateMetastatic colorectal cancer patientsDual antibody therapySafety of capecitabineResultsTwenty-three patientsFirst-line treatmentColorectal cancer patientsOverall response rateKRAS mutation statusEndothelial growth factorBevacizumab 7.5Capecitabine 850Cetuximab 400Growth factor receptorOxaliplatin 130