2018
Exploratory Analysis of Brigatinib Activity in Patients With Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer and Brain Metastases in Two Clinical Trials.
Camidge DR, Kim DW, Tiseo M, Langer CJ, Ahn MJ, Shaw AT, Huber RM, Hochmair MJ, Lee DH, Bazhenova LA, Gold KA, Ou SI, West HL, Reichmann W, Haney J, Clackson T, Kerstein D, Gettinger SN. Exploratory Analysis of Brigatinib Activity in Patients With Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer and Brain Metastases in Two Clinical Trials. Journal Of Clinical Oncology 2018, 36: 2693-2701. PMID: 29768119, DOI: 10.1200/jco.2017.77.5841.Peer-Reviewed Original ResearchConceptsIntracranial progression-free survivalBaseline brain metastasesALK-positive NSCLCBrain metastasesIntracranial ORRArm ALung cancerAnaplastic Lymphoma Kinase-Positive NonMedian intracranial progression-free survivalPhase I/II trialNext-generation ALK inhibitorsSmall cell lung cancerMeasurable brain metastasesPrior brain radiotherapyResults Most patientsPrimary end pointProgression-free survivalCell lung cancerIndependent review committeeInitial disease progressionAnaplastic lymphoma kinase (ALK) geneIntracranial efficacyII trialPrior radiationBrain radiotherapy
2017
Brigatinib (BRG) in patients (pts) with crizotinib (CRZ)-refractory ALK+ non-small cell lung cancer (NSCLC) and brain metastases in the pivotal randomized phase 2 ALTA trial.
Ou S, Tiseo M, Camidge D, Ahn M, Huber R, Hochmair M, Kim S, West H, Reckamp K, Molina J, Liu G, Delmonte A, Viteri Ramirez S, Bearz A, Summers Y, Reichmann W, Kerstein D, Gettinger S, Kim D. Brigatinib (BRG) in patients (pts) with crizotinib (CRZ)-refractory ALK+ non-small cell lung cancer (NSCLC) and brain metastases in the pivotal randomized phase 2 ALTA trial. Journal Of Clinical Oncology 2017, 35: e20502-e20502. DOI: 10.1200/jco.2017.35.15_suppl.e20502.Peer-Reviewed Original ResearchNon-small cell lung cancerBaseline brain metastasesBrain metastasesIndependent review committeeIntracranial efficacyCommon treatment-emergent adverse eventsNext-generation ALK inhibitorsTreatment-emergent adverse eventsFirst disease progressionCell lung cancerBlood CPKNSCLC ptsAdverse eventsAcceptable safetyLung cancerDisease progressionIntracranial responseALK inhibitorsBrigatinibMetastasisReview CommitteeGood responseEfficacyTrialsHypertensionDesign of ALTA-1L (ALK in lung cancer trial of brigatinib in first-line), a randomized phase 3 trial of brigatinib (BRG) versus crizotinib (CRZ) in tyrosine kinase inhibitor (TKI)-naive patients (pts) with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).
Tiseo M, Popat S, Gettinger S, Peters S, Haney J, Kerstein D, Camidge D. Design of ALTA-1L (ALK in lung cancer trial of brigatinib in first-line), a randomized phase 3 trial of brigatinib (BRG) versus crizotinib (CRZ) in tyrosine kinase inhibitor (TKI)-naive patients (pts) with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2017, 35: tps9098-tps9098. DOI: 10.1200/jco.2017.35.15_suppl.tps9098.Peer-Reviewed Original ResearchNon-small cell lung cancerProgression-free survivalObjective response rateRandomized phase 3 trialPhase 3 trialPrimary endpointTKI therapyPositive non-small cell lung cancerAdvanced anaplastic lymphoma kinaseNext-generation ALK inhibitorsRandomized phase 2 trialPrior TKI therapySafety/tolerabilityPhase 1/2 trialPhase 2 trialKaplan-Meier methodCell lung cancerDuration of responseIndependent review committeeLog-rank testPotent preclinical activityTyrosine kinase inhibitorsAnaplastic lymphoma kinaseNaive patientsNSCLC ptsBrigatinib 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
Ceritinib enables stereotactic radiosurgery to a previously untreatable symptomatic brain metastasis in a patient with ALK rearranged non-small cell lung cancer
Qian J, Yu J, Gettinger S, Chiang V. Ceritinib enables stereotactic radiosurgery to a previously untreatable symptomatic brain metastasis in a patient with ALK rearranged non-small cell lung cancer. Cancer Treatment And Research Communications 2016, 6: 17-19. DOI: 10.1016/j.ctrc.2016.02.002.Peer-Reviewed Original ResearchNon-small cell lung cancerAnaplastic lymphoma kinaseWhole-brain radiation therapySymptomatic brain metastasesBrain radiation therapyCell lung cancerBrain metastasesStereotactic radiosurgerySystemic therapyLung cancerRadiation therapyActive small-molecule tyrosine kinase inhibitorLarge symptomatic brain metastasisNext-generation ALK inhibitorsSmall molecule tyrosine kinase inhibitorsYear old Caucasian femaleMolecule tyrosine kinase inhibitorsGeneration ALK inhibitorsALK inhibitor crizotinibOld Caucasian femaleKey driver mutationsTyrosine kinase inhibitorsLocal therapyInhibitor crizotinibALK inhibitors