2020
Bempegaldesleukin (NKTR-214) plus Nivolumab in Patients with Advanced Solid Tumors: Phase I Dose-Escalation Study of Safety, Efficacy, and Immune Activation (PIVOT-02)
Diab A, Tannir NM, Bentebibel SE, Hwu P, Papadimitrakopoulou V, Haymaker C, Kluger HM, Gettinger SN, Sznol M, Tykodi SS, Curti BD, Tagliaferri MA, Zalevsky J, Hannah AL, Hoch U, Aung S, Fanton C, Rizwan A, Iacucci E, Liao Y, Bernatchez C, Hurwitz ME, Cho DC. Bempegaldesleukin (NKTR-214) plus Nivolumab in Patients with Advanced Solid Tumors: Phase I Dose-Escalation Study of Safety, Efficacy, and Immune Activation (PIVOT-02). Cancer Discovery 2020, 10: 1158-1173. PMID: 32439653, DOI: 10.1158/2159-8290.cd-19-1510.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungCarcinoma, Renal CellFemaleGene Expression Regulation, NeoplasticHumansImmune Checkpoint InhibitorsImmunotherapyInterleukin-2Kidney NeoplasmsLung NeoplasmsLymphocyte CountLymphocytes, Tumor-InfiltratingMaleMelanomaMiddle AgedNivolumabPolyethylene GlycolsProgrammed Cell Death 1 ReceptorTreatment OutcomeYoung AdultConceptsTreatment-related adverse eventsAdvanced solid tumorsPD-L1 statusSolid tumorsGrade 3/4 treatment-related adverse eventsPD-1/PD-L1 blockadeCommon treatment-related adverse eventsPhase I dose-escalation trialPoor prognostic risk factorsTotal objective response rateI dose-escalation studyI dose-escalation trialLongitudinal tumor biopsiesPD-L1 blockadeT-cell enhancementTreatment-related deathsObjective response ratePhase II doseDose-escalation studyDose-escalation trialDose-limiting toxicityFlu-like symptomsPrognostic risk factorsTumor-infiltrating lymphocytesCytotoxicity of CD8Phase 1 Trial of Pembrolizumab Administered Concurrently With Chemoradiotherapy for Locally Advanced Non–Small Cell Lung Cancer
Jabbour SK, Berman AT, Decker RH, Lin Y, Feigenberg SJ, Gettinger SN, Aggarwal C, Langer CJ, Simone CB, Bradley JD, Aisner J, Malhotra J. Phase 1 Trial of Pembrolizumab Administered Concurrently With Chemoradiotherapy for Locally Advanced Non–Small Cell Lung Cancer. JAMA Oncology 2020, 6: 848-855. PMID: 32077891, PMCID: PMC7042914, DOI: 10.1001/jamaoncol.2019.6731.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalCarboplatinCarcinoma, Non-Small-Cell LungChemoradiotherapyFemaleHumansImmune Checkpoint InhibitorsLung NeoplasmsMaleMiddle AgedNeoplasm StagingPaclitaxelProgrammed Cell Death 1 ReceptorTreatment OutcomeConceptsNon-small cell lung cancerProgression-free survivalStage III non-small cell lung cancerMedian progression-free survivalDose of pembrolizumabSafety expansion cohortPD-1 inhibitionCell lung cancerExpansion cohortLung cancerDay 29Eastern Cooperative Oncology Group performance status 0Advanced non-small cell lung cancerDay 1Cell death 1 (PD-1) inhibitionDeath ligand 1 (PD-L1) inhibitionDose-limiting toxic effectDeath-1 (PD-1) inhibitionDoses of pembrolizumabGrade 5 pneumonitisLeast grade 4Performance status 0PD-1 inhibitorsPhase 1 trialLeast grade 3Phase 1 study of epacadostat in combination with atezolizumab for patients with previously treated advanced nonsmall cell lung cancer
Hellmann MD, Gettinger S, Chow LQM, Gordon M, Awad MM, Cha E, Gong X, Zhou G, Walker C, Leopold L, Heist RS. Phase 1 study of epacadostat in combination with atezolizumab for patients with previously treated advanced nonsmall cell lung cancer. International Journal Of Cancer 2020, 147: 1963-1969. PMID: 32141617, PMCID: PMC7496129, DOI: 10.1002/ijc.32951.Peer-Reviewed Original ResearchConceptsNonsmall cell lung cancerTreatment-related adverse eventsDose-limiting toxicityCell lung cancerAdverse eventsLung cancerStage IIIB/IV nonsmall cell lung cancerFatal treatment-related adverse eventsAdvanced nonsmall cell lung cancerCell death ligand 1Grade 3 dehydrationGrade 3 hyponatremiaGrade 3/4 eventsPhase 1 studyPlatinum-based chemotherapyDeath ligand 1Dose of treatmentAutoimmune encephalitisEligible patientsIntravenous atezolizumabStable diseasePrimary endpointPartial responsePrior linesIDO expression
2019
The EGFR Exon 19 Mutant L747-A750>P Exhibits Distinct Sensitivity to Tyrosine Kinase Inhibitors in Lung Adenocarcinoma
Truini A, Starrett JH, Stewart T, Ashtekar K, Walther Z, Wurtz A, Lu D, Park JH, DeVeaux M, Song X, Gettinger S, Zelterman D, Lemmon MA, Goldberg SB, Politi K. The EGFR Exon 19 Mutant L747-A750>P Exhibits Distinct Sensitivity to Tyrosine Kinase Inhibitors in Lung Adenocarcinoma. Clinical Cancer Research 2019, 25: 6382-6391. PMID: 31182434, PMCID: PMC6825535, DOI: 10.1158/1078-0432.ccr-19-0780.Peer-Reviewed Original ResearchComparison of Survival Rates After a Combination of Local Treatment and Systemic Therapy vs Systemic Therapy Alone for Treatment of Stage IV Non–Small Cell Lung Cancer
Uhlig J, Case MD, Blasberg JD, Boffa DJ, Chiang A, Gettinger SN, Kim HS. Comparison of Survival Rates After a Combination of Local Treatment and Systemic Therapy vs Systemic Therapy Alone for Treatment of Stage IV Non–Small Cell Lung Cancer. JAMA Network Open 2019, 2: e199702. PMID: 31433481, PMCID: PMC6707019, DOI: 10.1001/jamanetworkopen.2019.9702.Peer-Reviewed Original ResearchMeSH KeywordsAblation TechniquesAdolescentAdultAgedAged, 80 and overAntineoplastic AgentsCarcinoma, Non-Small-Cell LungChemotherapy, AdjuvantComparative Effectiveness ResearchDatabases, FactualFemaleFollow-Up StudiesHumansLung NeoplasmsMaleMiddle AgedNeoplasm MetastasisNeoplasm StagingPneumonectomyProportional Hazards ModelsRadiotherapy, AdjuvantRetrospective StudiesSurvival RateTreatment OutcomeYoung AdultConceptsStage IV non-small cell lung cancerNon-small cell lung cancerPrimary tumor siteSuperior overall survivalSystemic therapySurgical resectionCell lung cancerExternal beam radiotherapyOverall survivalSurvival benefitLocal treatmentTumor siteTumor characteristicsLung cancerTreatment groupsMultivariable Cox proportional hazards regression modelsOligometastatic non-small cell lung cancerStage IV squamous cell carcinomaSurvival rateCox proportional hazards regression modelProportional hazards regression modelsComparative effectiveness research studyCancer-specific factorsNational Cancer DatabaseStage IV disease
2018
EGFR-Mutant Adenocarcinomas That Transform to Small-Cell Lung Cancer and Other Neuroendocrine Carcinomas: Clinical Outcomes
Marcoux N, Gettinger SN, O’Kane G, Arbour KC, Neal JW, Husain H, Evans TL, Brahmer JR, Muzikansky A, Bonomi PD, del Prete S, Wurtz A, Farago AF, Dias-Santagata D, Mino-Kenudson M, Reckamp KL, Yu HA, Wakelee HA, Shepherd FA, Piotrowska Z, Sequist LV. EGFR-Mutant Adenocarcinomas That Transform to Small-Cell Lung Cancer and Other Neuroendocrine Carcinomas: Clinical Outcomes. Journal Of Clinical Oncology 2018, 37: 278-285. PMID: 30550363, PMCID: PMC7001776, DOI: 10.1200/jco.18.01585.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarcinoma, Non-Small-Cell LungClass I Phosphatidylinositol 3-KinasesErbB ReceptorsFemaleGenetic Predisposition to DiseaseHumansLung NeoplasmsMaleMiddle AgedMutationNeoplasm GradingNorth AmericaPhenotypeRetinoblastoma Binding ProteinsRetrospective StudiesSmall Cell Lung CarcinomaTime FactorsTreatment OutcomeTumor Suppressor Protein p53Ubiquitin-Protein LigasesConceptsNon-small cell lung cancerSmall cell lung cancerEGFR-mutant non-small cell lung cancerSCLC transformationLung cancerNeuroendocrine carcinomaEGFR mutationsDe novo small cell lung cancersInitial lung cancer diagnosisHigh-grade neuroendocrine carcinomaEGFR tyrosine kinase inhibitorsT790M positivityMedian overall survivalCell lung cancerTyrosine kinase inhibitorsHigh response rateEGFR-mutant adenocarcinomaLung cancer diagnosisCNS metastasesCheckpoint inhibitorsMedian survivalOverall survivalClinical courseMixed histologyClinical outcomesOncolytic virus immunotherapy: future prospects for oncology
Raja J, Ludwig JM, Gettinger SN, Schalper KA, Kim HS. Oncolytic virus immunotherapy: future prospects for oncology. Journal For ImmunoTherapy Of Cancer 2018, 6: 140. PMID: 30514385, PMCID: PMC6280382, DOI: 10.1186/s40425-018-0458-z.Peer-Reviewed Original ResearchConceptsOncolytic virusesSevere immune-related adverse eventsImmune-related adverse eventsAnti-tumor immune responseEarly-stage clinical trialsImmune checkpoint inhibitorsSerious adverse effectsOncolytic viral therapyLimited therapeutic responseAnti-cancer treatmentLocal target cellsCheckpoint inhibitorsSalvage therapyTolerability profileCytotoxic chemotherapyAdverse eventsImmune dysregulationOncologic careTherapeutic optionsTumor bedSuch therapyTherapeutic responseClinical trialsNovel therapiesViral therapyLong-term survival follow-up of atezolizumab in combination with platinum-based doublet chemotherapy in patients with advanced non–small-cell lung cancer
Liu SV, Camidge DR, Gettinger SN, Giaccone G, Heist RS, Hodi FS, Ready NE, Zhang W, Wallin J, Funke R, Waterkamp D, Foster P, Iizuka K, Powderly J. Long-term survival follow-up of atezolizumab in combination with platinum-based doublet chemotherapy in patients with advanced non–small-cell lung cancer. European Journal Of Cancer 2018, 101: 114-122. PMID: 30053670, DOI: 10.1016/j.ejca.2018.06.033.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCarboplatinCarcinoma, Non-Small-Cell LungDisease-Free SurvivalFemaleFollow-Up StudiesHumansLung NeoplasmsMaleMiddle AgedNeutropeniaSurvival AnalysisTime FactorsTreatment OutcomeConceptsObjective response rateProgression-free survivalCell lung cancerOverall survivalLung cancerAnti-programmed death ligand 1 antibodyGrade III/IV adverse eventsConfirmed objective response rateMedian progression-free survivalPlatinum-based doublet chemotherapyStandard first-line therapyDeath ligand 1 antibodyCell death protein 1Availability of immunotherapyMedian overall survivalFirst-line therapyLigand 1 antibodyDeath protein 1Actionable gene alterationsLong-term survivalDoublet chemotherapyImmunotherapy combinationsNab-PacNab-paclitaxelAdverse eventsEarly Assessment of Lung Cancer Immunotherapy Response via Circulating Tumor DNA
Goldberg SB, Narayan A, Kole AJ, Decker RH, Teysir J, Carriero NJ, Lee A, Nemati R, Nath SK, Mane SM, Deng Y, Sukumar N, Zelterman D, Boffa DJ, Politi K, Gettinger S, Wilson LD, Herbst RS, Patel AA. Early Assessment of Lung Cancer Immunotherapy Response via Circulating Tumor DNA. Clinical Cancer Research 2018, 24: 1872-1880. PMID: 29330207, PMCID: PMC5899677, DOI: 10.1158/1078-0432.ccr-17-1341.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerImmune checkpoint inhibitorsCtDNA responseCheckpoint inhibitorsCtDNA levelsMetastatic non-small cell lung cancerImmune checkpoint inhibitor therapySuperior progression-free survivalRadiographic tumor sizeCheckpoint inhibitor therapyProgression-free survivalSuperior overall survivalTumor DNA levelsCell lung cancerAllele fractionClin Cancer ResMultigene next-generation sequencingMutant allele fractionTumor cell deathInhibitor therapyOverall survivalRadiographic responseImmunotherapy efficacyImmunotherapy responseMedian timeNivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases
Vokes EE, Ready N, Felip E, Horn L, Burgio MA, Antonia SJ, Frontera O, Gettinger S, Holgado E, Spigel D, Waterhouse D, Domine M, Garassino M, Chow LQM, Blumenschein G, Barlesi F, Coudert B, Gainor J, Arrieta O, Brahmer J, Butts C, Steins M, Geese WJ, Li A, Healey D, Crinò L. Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases. Annals Of Oncology 2018, 29: 959-965. PMID: 29408986, DOI: 10.1093/annonc/mdy041.Peer-Reviewed Original ResearchConceptsBaseline liver metastasesImproved overall survivalLiver metastasesCell lung cancerOverall survivalOS benefitCheckMate 017Nonsquamous NSCLCLung cancerSubgroup analysisAnti-programmed death-1 (PD-1) antibody nivolumabNivolumab-treated patientsImmune checkpoint inhibitorsPrimary end pointHepatic adverse eventsPhase III trialsFavorable safety profileNew safety concernsCheckMate 057Advanced NSCLCCheckpoint inhibitorsAdverse eventsIII trialsOS ratesAntibody nivolumab
2017
Brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase–Positive Non–Small-Cell Lung Cancer: A Randomized, Multicenter Phase II Trial
Kim DW, Tiseo M, Ahn MJ, Reckamp KL, Hansen KH, Kim SW, Huber RM, West HL, Groen HJM, Hochmair MJ, Leighl NB, Gettinger SN, Langer CJ, Paz-Ares Rodríguez LG, Smit EF, Kim ES, Reichmann W, Haluska FG, Kerstein D, Camidge DR. Brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase–Positive Non–Small-Cell Lung Cancer: A Randomized, Multicenter Phase II Trial. Journal Of Clinical Oncology 2017, 35: jco.2016.71.590. PMID: 28475456, DOI: 10.1200/jco.2016.71.5904.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAnaplastic Lymphoma KinaseAntineoplastic AgentsBrain NeoplasmsCarcinoma, Non-Small-Cell LungCoughCrizotinibDiarrheaDisease ProgressionDisease-Free SurvivalFemaleHeadacheHumansLung NeoplasmsMaleMiddle AgedNauseaOrganophosphorus CompoundsProspective StudiesPyrazolesPyridinesPyrimidinesReceptor Protein-Tyrosine KinasesRetreatmentTreatment OutcomeYoung AdultConceptsObjective response rateProgression-free survivalBrain metastasesArm AAdverse eventsLung cancerInvestigator-assessed median progression-free survivalCommon treatment-emergent adverse eventsPositive non-small cell lung cancerNon-small cell lung cancerMedian progression-free survivalMulticenter phase II trialNext-generation ALK inhibitorsTreatment-emergent adverse eventsIntracranial objective response rateBaseline brain metastasesCrizotinib-treated patientsMeasurable brain metastasesPulmonary adverse eventsPrimary end pointPhase II trialCell lung cancerALK-positive NSCLCAnaplastic lymphoma kinase (ALK) geneAnaplastic lymphoma kinaseA phase Ib/II study of cabozantinib (XL184) with or without erlotinib in patients with non-small cell lung cancer
Wakelee HA, Gettinger S, Engelman J, Jänne PA, West H, Subramaniam DS, Leach J, Wax M, Yaron Y, Miles DR, Lara PN. A phase Ib/II study of cabozantinib (XL184) with or without erlotinib in patients with non-small cell lung cancer. Cancer Chemotherapy And Pharmacology 2017, 79: 923-932. PMID: 28352985, PMCID: PMC5403837, DOI: 10.1007/s00280-017-3283-z.Peer-Reviewed Original ResearchConceptsObjective response ratePhase Ib/II studyII studyPhase INon-small cell lung cancerFrequent dose-limiting toxicityPhase IIDose of cabozantinibDose-limiting toxicityResultsSixty-four patientsCell lung cancerMulti-kinase inhibitorProgressive NSCLCStable diseaseCombination armPartial responseFrequent AEsErlotinib treatmentLung cancerEGFR mutationsErlotinib pharmacokineticsCabozantinibPatientsPrimary objectiveResponse rate
2015
Preliminary Safety, Pharmacokinetics, and Efficacy of Regorafenib, Cisplatin, and Pemetrexed in Patients With Advanced Nonsquamous Non–Small-Cell Lung Cancers
Hellmann MD, Sturm I, Trnkova ZJ, Lettieri J, Diefenbach K, Rizvi NA, Gettinger SN. Preliminary Safety, Pharmacokinetics, and Efficacy of Regorafenib, Cisplatin, and Pemetrexed in Patients With Advanced Nonsquamous Non–Small-Cell Lung Cancers. Clinical Lung Cancer 2015, 16: 514-522. PMID: 26003007, PMCID: PMC4750397, DOI: 10.1016/j.cllc.2015.04.003.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabCarcinoma, Non-Small-Cell LungCisplatinContraindicationsDrug InteractionsFemaleHumansLung NeoplasmsMaleMiddle AgedNeoplasm StagingNeovascularization, PathologicPemetrexedPhenylurea CompoundsPyridinesSurvival AnalysisTreatment OutcomeConceptsEfficacy of regorafenibMedian progression-free survivalChemotherapy-naive patientsProgression-free survivalPhase I trialCell lung cancerLung cancerAcceptable tolerabilityPartial responsePotent antiangiogenic activityI trialStandard dosesPK interactionsAdvanced nonsquamous non-small cell lung cancerNonsquamous non-small cell lung cancerTreatment-related grade 3 adverse eventsNon-small cell lung cancerGrade 3 adverse eventsKinase inhibitorsAntiangiogenic activityMinor pharmacokinetic interactionCombination of bevacizumabAdvanced colorectal cancerGastrointestinal stromal tumorsAdverse eventsOverall Survival and Long-Term Safety of Nivolumab (Anti–Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non–Small-Cell Lung Cancer
Gettinger SN, Horn L, Gandhi L, Spigel DR, Antonia SJ, Rizvi NA, Powderly JD, Heist RS, Carvajal RD, Jackman DM, Sequist LV, Smith DC, Leming P, Carbone DP, Pinder-Schenck MC, Topalian SL, Hodi FS, Sosman JA, Sznol M, McDermott DF, Pardoll DM, Sankar V, Ahlers CM, Salvati M, Wigginton JM, Hellmann MD, Kollia GD, Gupta AK, Brahmer JR. Overall Survival and Long-Term Safety of Nivolumab (Anti–Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non–Small-Cell Lung Cancer. Journal Of Clinical Oncology 2015, 33: 2004-2012. PMID: 25897158, PMCID: PMC4672027, DOI: 10.1200/jco.2014.58.3708.Peer-Reviewed Original ResearchConceptsOverall survivalLong-term safetyAdvanced NSCLCLung cancerDeath-1 immune checkpoint inhibitor antibodyAdvanced non-small cell lung cancerNon-small cell lung cancerImmune checkpoint inhibitor antibodyTreatment-related adverse eventsCheckpoint inhibitor antibodyTreatment-related deathsMedian overall survivalMedian response durationAdvanced solid tumorsPhase I trialCell lung cancerRandomized clinical trialsFurther clinical developmentHuman immunoglobulin G4Nivolumab 1Nivolumab monotherapyExpansion cohortLast doseNonsquamous NSCLCAdverse eventsPhase 1b study of the mammalian target of rapamycin inhibitor sirolimus in combination with nanoparticle albumin–bound paclitaxel in patients with advanced solid tumors
Abu-Khalaf MM, Baumgart MA, Gettinger SN, Doddamane I, Tuck DP, Hou S, Chen N, Sullivan C, Lezon-Geyda K, Zelterman D, Hatzis C, Deshpande H, Digiovanna MP, Azodi M, Schwartz PE, Harris LN. Phase 1b study of the mammalian target of rapamycin inhibitor sirolimus in combination with nanoparticle albumin–bound paclitaxel in patients with advanced solid tumors. Cancer 2015, 121: 1817-1826. PMID: 25649370, DOI: 10.1002/cncr.29254.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityIntravenous nab-paclitaxelPhase 1b studyAdvanced solid tumorsNab-paclitaxelFDG activityDay 1Solid tumorsNanoparticle albumin-bound paclitaxelMammalian targetWeekly oral doseAcceptable safety profileRapamycin inhibitor sirolimusAlbumin-bound paclitaxelClinical trial endpointsExploratory gene expression analysisPositron emission tomographyStable diseaseTaxane therapyPartial responseWeekly doseComplete responseOral sirolimusPharmacodynamic assessmentOral dose
2014
Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients
Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, Kohrt HE, Horn L, Lawrence DP, Rost S, Leabman M, Xiao Y, Mokatrin A, Koeppen H, Hegde PS, Mellman I, Chen DS, Hodi FS. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 2014, 515: 563-567. PMID: 25428504, PMCID: PMC4836193, DOI: 10.1038/nature14011.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedB7-H1 AntigenBiomarkersChemokine CX3CL1Clinical ProtocolsCTLA-4 AntigenDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticHumansImmunotherapyLymphocytes, Tumor-InfiltratingMaleMiddle AgedNeoplasmsTreatment OutcomeYoung AdultDual Inhibition of EGFR with Afatinib and Cetuximab in Kinase Inhibitor–Resistant EGFR-Mutant Lung Cancer with and without T790M Mutations
Janjigian YY, Smit EF, Groen HJ, Horn L, Gettinger S, Camidge DR, Riely GJ, Wang B, Fu Y, Chand VK, Miller VA, Pao W. Dual Inhibition of EGFR with Afatinib and Cetuximab in Kinase Inhibitor–Resistant EGFR-Mutant Lung Cancer with and without T790M Mutations. Cancer Discovery 2014, 4: 1036-1045. PMID: 25074459, PMCID: PMC4155006, DOI: 10.1158/2159-8290.cd-14-0326.Peer-Reviewed Original ResearchConceptsEGFR-mutant lung cancerT790M mutationLung cancerM mutationGrade 3/4 adverse eventsMedian progression-free survivalEGFR T790M mutationErlotinib/gefitinibRobust clinical activityT790M-negative tumorsManageable safety profileObjective response ratePhase Ib studyProgression-free survivalMutant lung cancerGefitinib/erlotinibFirst clinical proofReversible EGFR inhibitorsAdverse eventsMedian durationObjective responseSafety profilePreclinical hypothesisEGFR mutationsClinical activity
2013
Phase I Study of the Hedgehog Pathway Inhibitor IPI-926 in Adult Patients with Solid Tumors
Jimeno A, Weiss GJ, Miller WH, Gettinger S, Eigl BJ, Chang AL, Dunbar J, Devens S, Faia K, Skliris G, Kutok J, Lewis KD, Tibes R, Sharfman WH, Ross RW, Rudin CM. Phase I Study of the Hedgehog Pathway Inhibitor IPI-926 in Adult Patients with Solid Tumors. Clinical Cancer Research 2013, 19: 2766-2774. PMID: 23575478, PMCID: PMC3694426, DOI: 10.1158/1078-0432.ccr-12-3654.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAlanine TransaminaseAlopeciaArea Under CurveAspartate AminotransferasesDose-Response Relationship, DrugDrug Administration ScheduleFatigueFemaleFollow-Up StudiesHedgehog ProteinsHumansMaleMetabolic Clearance RateMiddle AgedNauseaNeoplasmsSignal TransductionSpasmTreatment OutcomeVeratrum AlkaloidsConceptsBasal cell carcinomaDose-limiting toxicityInhibitor-naïve patientsIPI-926Alanine aminotransferaseSolid tumorsAspartate aminotransferaseAccelerated titration scheduleDose-escalation cohortsPhase II doseResponse Evaluation CriteriaSingle-agent activityHuman phase ISolid Tumors assessmentHematologic toxicityStarting doseAdult patientsStandard therapyMuscle spasmTitration scheduleReversible elevationCell carcinomaQD dosingTumor assessmentPharmacokinetic profileHigh SOX2 Levels Predict Better Outcome in Non-Small Cell Lung Carcinomas
Velcheti V, Schalper K, Yao X, Cheng H, Kocoglu M, Dhodapkar K, Deng Y, Gettinger S, Rimm DL. High SOX2 Levels Predict Better Outcome in Non-Small Cell Lung Carcinomas. PLOS ONE 2013, 8: e61427. PMID: 23620753, PMCID: PMC3631238, DOI: 10.1371/journal.pone.0061427.Peer-Reviewed Original ResearchConceptsSquamous cell carcinomaLonger survivalTissue microarrayMultivariate analysisIndependent lung cancer cohortsIndependent positive prognostic markerSOX2 levelsNon-small cell lung carcinomaQuantitative immunofluorescenceLung squamous cell carcinomaSecond independent validation cohortSOX2 expressionHigh SOX2 levelsLog rank pSOX2 overexpressionPositive prognostic markerRisk of deathClinico-pathological characteristicsClinico-pathological variablesCox univariate analysisIndependent validation cohortCell lung carcinomaLung cancer cohortNSCLC patientsOverall survival
2010
High expression of BCL-2 predicts favorable outcome in non-small cell lung cancer patients with non squamous histology
Anagnostou VK, Lowery FJ, Zolota V, Tzelepi V, Gopinath A, Liceaga C, Panagopoulos N, Frangia K, Tanoue L, Boffa D, Gettinger S, Detterbeck F, Homer RJ, Dougenis D, Rimm DL, Syrigos KN. High expression of BCL-2 predicts favorable outcome in non-small cell lung cancer patients with non squamous histology. BMC Cancer 2010, 10: 186. PMID: 20459695, PMCID: PMC2875218, DOI: 10.1186/1471-2407-10-186.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAgedBiomarkers, TumorCarcinoma, Large CellCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellCell DifferentiationCohort StudiesConnecticutFemaleGreeceHumansKaplan-Meier EstimateLung NeoplasmsMaleMiddle AgedNeoplasm StagingPredictive Value of TestsProportional Hazards ModelsProto-Oncogene Proteins c-bcl-2Reproducibility of ResultsRetrospective StudiesRisk AssessmentRisk FactorsTime FactorsTreatment OutcomeUp-RegulationConceptsNon-small cell lung cancer patientsCell lung cancer patientsNon-squamous tumorsLung cancer patientsBcl-2 expressionNSCLC patientsCancer patientsBcl-2Favorable outcomeIndependent cohortSmall cell lung cancer patientsIndependent lower riskNon-squamous histologySubgroup of patientsHigh expressersSquamous cell carcinomaHigh Bcl-2 expressionBcl-2 protein levelsSquamous histologyMedian survivalPrognostic factorsValidation cohortCell carcinomaPathological characteristicsPrognostic stratification