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 kinase
2016
Activity and safety of brigatinib in ALK-rearranged non-small-cell lung cancer and other malignancies: a single-arm, open-label, phase 1/2 trial
Gettinger SN, Bazhenova LA, Langer CJ, Salgia R, Gold KA, Rosell R, Shaw AT, Weiss GJ, Tugnait M, Narasimhan NI, Dorer DJ, Kerstein D, Rivera VM, Clackson T, Haluska FG, Camidge DR. Activity and safety of brigatinib in ALK-rearranged non-small-cell lung cancer and other malignancies: a single-arm, open-label, phase 1/2 trial. The Lancet Oncology 2016, 17: 1683-1696. PMID: 27836716, DOI: 10.1016/s1470-2045(16)30392-8.Peer-Reviewed Original ResearchConceptsTreatment-emergent adverse eventsPhase 2 doseCell lung cancerObjective responsePrimary endpointAdvanced malignanciesAdverse eventsLung cancerGrade 3ALK inhibitorsPrevious EGFR-tyrosine kinase inhibitorsSerious treatment-emergent adverse eventsCohort 5Phase 2 primary endpointRandomised phase 2 trialPotential new treatment optionAnaplastic lymphoma kinase (ALK) gene rearrangementEGFR tyrosine kinase inhibitorsCommon grade 3Acceptable safety profilePhase 2 trialProportion of patientsTotal daily dosesPotent preclinical activityNew treatment optionsPD-1 Axis Inhibitors in EGFR- and ALK-Driven Lung Cancer: Lost Cause?
Gettinger S, Politi K. PD-1 Axis Inhibitors in EGFR- and ALK-Driven Lung Cancer: Lost Cause? Clinical Cancer Research 2016, 22: 4539-4541. PMID: 27470969, PMCID: PMC5653962, DOI: 10.1158/1078-0432.ccr-16-1401.Peer-Reviewed Original Research
2014
Perfect ALKemy: Optimizing the Use of ALK-Directed Therapies in Lung Cancer
Politi K, Gettinger S. Perfect ALKemy: Optimizing the Use of ALK-Directed Therapies in Lung Cancer. Clinical Cancer Research 2014, 20: 5576-5578. PMID: 25228532, PMCID: PMC4401422, DOI: 10.1158/1078-0432.ccr-14-2306.Commentaries, Editorials and LettersMeSH KeywordsCarbazolesDrug Resistance, NeoplasmHumansMutationPiperidinesProtein Kinase InhibitorsReceptor Protein-Tyrosine Kinases
2013
A Clinical Model for Identifying Radiosensitive Tumor Genotypes in Non–Small Cell Lung Cancer
Johung KL, Yao X, Li F, Yu JB, Gettinger SN, Goldberg S, Decker RH, Hess JA, Chiang VL, Contessa JN. A Clinical Model for Identifying Radiosensitive Tumor Genotypes in Non–Small Cell Lung Cancer. Clinical Cancer Research 2013, 19: 5523-5532. PMID: 23897899, DOI: 10.1158/1078-0432.ccr-13-0836.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnaplastic Lymphoma KinaseAntineoplastic AgentsBrain NeoplasmsCarcinoma, Non-Small-Cell LungErbB ReceptorsFemaleGenotypeHumansLung NeoplasmsMaleMiddle AgedMutationProtein Kinase InhibitorsRadiation ToleranceReceptor Protein-Tyrosine KinasesRecurrenceTranslocation, GeneticTumor BurdenConceptsNon-small cell lung cancerCell lung cancerEML4-ALK translocationGamma knife treatmentLocal controlTumor genotypeLung cancerEGFR mutationsCox proportional hazards modelDistant brain controlDistant brain recurrenceGamma knife radiotherapyEGFR kinase domain mutationsSuperior local controlField local controlKRAS mutation statusProportional hazards modelKinase domain mutationsEGF receptorMetastasis sizeBrain recurrenceBrain metastasesField recurrenceClinical outcomesIndependent predictorsIdentification of EGFR mutation, KRAS mutation, and ALK gene rearrangement in cytological specimens of primary and metastatic lung adenocarcinoma
Cai G, Wong R, Chhieng D, Levy GH, Gettinger SN, Herbst RS, Puchalski JT, Homer RJ, Hui P. Identification of EGFR mutation, KRAS mutation, and ALK gene rearrangement in cytological specimens of primary and metastatic lung adenocarcinoma. Cancer Cytopathology 2013, 121: 500-507. PMID: 23495083, DOI: 10.1002/cncy.21288.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overAnaplastic Lymphoma KinaseBiomarkers, TumorBone NeoplasmsCytodiagnosisDNA, NeoplasmErbB ReceptorsFeasibility StudiesFemaleGene RearrangementHumansIn Situ Hybridization, FluorescenceLiver NeoplasmsLung NeoplasmsMaleMiddle AgedMutationNeoplasm Recurrence, LocalPrognosisProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)Ras ProteinsReal-Time Polymerase Chain ReactionReceptor Protein-Tyrosine KinasesSoft Tissue NeoplasmsYoung AdultConceptsALK gene rearrangementMetastatic lung adenocarcinomaEGFR mutationsKRAS mutationsMetastatic tumorsEpidermal growth factor receptorLung adenocarcinomaCytological specimensGene rearrangementsMolecular testsMolecular alterationsKirsten rat sarcoma viral oncogene homolog (KRAS) mutationsALK gene rearrangement analysisAnaplastic lymphoma kinase (ALK) gene rearrangementEGFR T790M mutationRat sarcoma viral oncogene homolog mutationsCases of lungT790M mutationImportant therapeutic implicationsFine needle aspiratesGene rearrangement analysisCell block materialGrowth factor receptorRecurrent lungRecurrent adenocarcinoma
2010
Activity of IPI-504, a Novel Heat-Shock Protein 90 Inhibitor, in Patients With Molecularly Defined Non–Small-Cell Lung Cancer
Sequist LV, Gettinger S, Senzer NN, Martins RG, Jänne PA, Lilenbaum R, Gray JE, Iafrate AJ, Katayama R, Hafeez N, Sweeney J, Walker JR, Fritz C, Ross RW, Grayzel D, Engelman JA, Borger DR, Paez G, Natale R. Activity of IPI-504, a Novel Heat-Shock Protein 90 Inhibitor, in Patients With Molecularly Defined Non–Small-Cell Lung Cancer. Journal Of Clinical Oncology 2010, 28: 4953-4960. PMID: 20940188, PMCID: PMC4676802, DOI: 10.1200/jco.2010.30.8338.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnaplastic Lymphoma KinaseBenzoquinonesCarcinoma, Non-Small-Cell LungErbB ReceptorsFemaleGene RearrangementHSP90 Heat-Shock ProteinsHumansLactams, MacrocyclicLung NeoplasmsMaleMiddle AgedMutationProspective StudiesProtein-Tyrosine KinasesReceptor Protein-Tyrosine KinasesConceptsObjective response rateProgression-free survivalCell lung cancerIPI-504Lung cancerEpidermal growth factor receptor tyrosine kinase inhibitor therapyUnited States cancer centersTyrosine kinase inhibitor therapyState Cancer CenterCommon adverse eventsLiver function abnormalitiesPhase II studyOverall study populationKinase inhibitor therapyHeat shock protein 90 inhibitorNovel heat shock protein 90 inhibitorALK gene rearrangementStable diseaseAdvanced NSCLCAdverse eventsFunction abnormalitiesII studyPartial responseInhibitor therapyPrimary outcome