2019
Brigatinib in Crizotinib-Refractory ALK+ NSCLC: 2-Year Follow-up on Systemic and Intracranial Outcomes in the Phase 2 ALTA Trial
Huber RM, Hansen KH, Paz-Ares Rodríguez L, West HL, Reckamp KL, Leighl NB, Tiseo M, Smit EF, Kim DW, Gettinger SN, Hochmair MJ, Kim SW, Langer CJ, Ahn MJ, Kim ES, Kerstein D, Groen HJM, Camidge DR. Brigatinib in Crizotinib-Refractory ALK+ NSCLC: 2-Year Follow-up on Systemic and Intracranial Outcomes in the Phase 2 ALTA Trial. Journal Of Thoracic Oncology 2019, 15: 404-415. PMID: 31756496, DOI: 10.1016/j.jtho.2019.11.004.Peer-Reviewed Original ResearchConceptsProgression-free survivalObjective response rateIntracranial objective response rateOverall survivalIntracranial PFSResponse rateEnd pointIntracranial responseBrain lesionsCentral nervous system metastasesSolid Tumors version 1.1Intracranial progression-free survivalCrizotinib-refractory patientsMedian overall survivalNervous system metastasesNew safety findingsPrimary end pointSecondary end pointsTarget lesion responseResponse Evaluation CriteriaIndependent review committeeDepth of responseImportant end pointIntracranial outcomesOral brigatinibA phase III randomized study of nivolumab plus ipilimumab versus nivolumab for previously treated patients with stage IV squamous cell lung cancer and no matching biomarker (Lung-MAP Sub-Study S1400I, NCT02785952).
Bazhenova L, Redman M, Gettinger S, Hirsch F, Mack P, Schwartz L, Gandara D, Bradley J, Stinchcombe T, Leighl N, Ramalingam S, Tavernier S, Minichiello K, Kelly K, Papadimitrakopoulou V, Herbst R. A phase III randomized study of nivolumab plus ipilimumab versus nivolumab for previously treated patients with stage IV squamous cell lung cancer and no matching biomarker (Lung-MAP Sub-Study S1400I, NCT02785952). Journal Of Clinical Oncology 2019, 37: 9014-9014. DOI: 10.1200/jco.2019.37.15_suppl.9014.Peer-Reviewed Original ResearchInvestigator-assessed progression-free survivalOverall survivalInterim analysisStage IV squamous cell lung cancerSquamous cell lung cancerGrade 5 AEsImmunotherapy-naïve patientsStudies of nivolumabTreatment-related AEsPD-L1 expressionProgression-free survivalPhase IIICell lung cancerECOG 0Primary endpointRECIST 1.1Baseline characteristicsPD-L1Lung cancerLung-MAPNivolumabStage IVPatientsResponse rateMaster protocols
2018
FIR: Efficacy, Safety, and Biomarker Analysis of a Phase II Open-Label Study of Atezolizumab in PD-L1–Selected Patients With NSCLC
Spigel DR, Chaft JE, Gettinger S, Chao BH, Dirix L, Schmid P, Chow LQM, Hicks RJ, Leon L, Fredrickson J, Kowanetz M, Sandler A, Funke R, Rizvi NA. FIR: Efficacy, Safety, and Biomarker Analysis of a Phase II Open-Label Study of Atezolizumab in PD-L1–Selected Patients With NSCLC. Journal Of Thoracic Oncology 2018, 13: 1733-1742. PMID: 29775807, PMCID: PMC7455890, DOI: 10.1016/j.jtho.2018.05.004.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsObjective response ratePD-L1 expressionAdverse eventsCohort 1Immune cell PD-L1 expressionInvestigator-assessed objective response ratePhase II open-label studyResponse rateIC PD-L1 expressionTumor cellsBaseline tumor samplesOpen-label studyPhase II studyProgression-free survivalResponse Evaluation CriteriaDuration of responseAtezolizumab monotherapyAdvanced NSCLCBrain metastasesMonotherapy studiesPrimary endpointSecondary endpointsII studyOverall survivalBrigatinib versus Crizotinib in ALK-Positive Non–Small-Cell Lung Cancer
Camidge DR, Kim HR, Ahn MJ, Yang JC, Han JY, Lee JS, Hochmair MJ, Li JY, Chang GC, Lee KH, Gridelli C, Delmonte A, Garcia Campelo R, Kim DW, Bearz A, Griesinger F, Morabito A, Felip E, Califano R, Ghosh S, Spira A, Gettinger SN, Tiseo M, Gupta N, Haney J, Kerstein D, Popat S. Brigatinib versus Crizotinib in ALK-Positive Non–Small-Cell Lung Cancer. New England Journal Of Medicine 2018, 379: 2027-2039. PMID: 30280657, DOI: 10.1056/nejmoa1810171.Peer-Reviewed Original ResearchConceptsProgression-free survivalALK-positive NSCLCAdvanced ALK-positive NSCLCObjective response rateFirst interim analysisALK inhibitorsLung cancerIntracranial responseInterim analysisNext-generation anaplastic lymphoma kinase (ALK) inhibitorResponse rateConfirmed objective response rateEnd pointSmall cell lung cancerBlinded independent central reviewAnaplastic lymphoma kinase inhibitorsEfficacy of brigatinibPrimary end pointSecondary end pointsPhase 3 trialALK-Positive NonCell lung cancerIndependent central reviewNew safety concernsCrizotinib group
2017
Activity of brigatinib (BRG) in crizotinib (CRZ)-resistant ALK+ NSCLC patients (pts) according to ALK plasma mutation status.
Bazhenova L, Hodgson J, Langer C, Simon G, Gettinger S, Ou S, Reckamp K, West H, Chiappori A, Koh H, Molina J, Shaw A, Patel J, Favaro J, Haney J, Reichmann W, Kerstein D, Rivera V, Camidge D. Activity of brigatinib (BRG) in crizotinib (CRZ)-resistant ALK+ NSCLC patients (pts) according to ALK plasma mutation status. Journal Of Clinical Oncology 2017, 35: 9065-9065. DOI: 10.1200/jco.2017.35.15_suppl.9065.Peer-Reviewed Original ResearchSecondary ALK mutationsNSCLC ptsALK mutationsALK fusionMutation statusObjective response ratePlasma samplesALK mutation statusSelective ALK inhibitorNSCLC patientsClinical activityEvaluable samplesALK inhibitorsResistance patternsSecondary resistanceTherapeutic implicationsComplex mutation patternsResponse rateBrigatinibPlasma specimensWild-type ALKALKTrialsGood responseMutation patternsBrigatinib (BRG) in crizotinib (CRZ)-refractory ALK+ non-small cell lung cancer (NSCLC): Updates from ALTA, a pivotal randomized phase 2 trial.
Ahn M, Camidge D, Tiseo M, Reckamp K, Holmskov Hansen K, Kim S, Huber R, West H, Groen H, Hochmair M, Leighl N, Gettinger S, Langer C, Paz-Ares L, Smit E, Kim E, Reichmann W, Kerstein D, Kim D. Brigatinib (BRG) in crizotinib (CRZ)-refractory ALK+ non-small cell lung cancer (NSCLC): Updates from ALTA, a pivotal randomized phase 2 trial. Journal Of Clinical Oncology 2017, 35: e20503-e20503. DOI: 10.1200/jco.2017.35.15_suppl.e20503.Peer-Reviewed Original ResearchNon-small cell lung cancerObjective response rateRandomized phase 2 trialPhase 2 trialAdverse eventsBrain metastasesMost common treatment-emergent adverse eventsCommon treatment-emergent adverse eventsTreatment-emergent adverse eventsIntracranial objective response rateBaseline brain metastasesPulmonary adverse eventsPhase 1/2 trialCell lung cancerRECIST v1.1Primary endpointNSCLC patientsMedian ageAcceptable safetyLung cancerDisease progressionDose reductionDose levelsResponse rateBrigatinibA 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
2016
Nivolumab in Combination With Platinum‐Based Doublet Chemotherapy for First-Line Treatment of Advanced Non–Small-Cell Lung Cancer
Rizvi NA, Hellmann MD, Brahmer JR, Juergens RA, Borghaei H, Gettinger S, Chow LQ, Gerber DE, Laurie SA, Goldman JW, Shepherd FA, Chen AC, Shen Y, Nathan FE, Harbison CT, Antonia S. Nivolumab in Combination With Platinum‐Based Doublet Chemotherapy for First-Line Treatment of Advanced Non–Small-Cell Lung Cancer. Journal Of Clinical Oncology 2016, 34: 2969-2979. PMID: 27354481, PMCID: PMC5569693, DOI: 10.1200/jco.2016.66.9861.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenCarboplatinCarcinoma, Non-Small-Cell LungCisplatinCohort StudiesDeoxycytidineDisease-Free SurvivalDose-Response Relationship, DrugErbB ReceptorsFemaleGemcitabineHumansLung NeoplasmsMaleMiddle AgedNivolumabPemetrexedProto-Oncogene Proteins p21(ras)Survival RateConceptsPlatinum-based doublet chemotherapyTreatment-related adverse eventsProgression-free survival ratesDeath ligand 1 (PD-L1) expressionObjective response ratePercent of patientsLigand 1 expressionAdverse eventsPaclitaxel-carboplatinDoublet chemotherapyOverall survivalOS ratesLung cancerDeath-1 immune checkpoint inhibitor antibodyAdvanced non-small cell lung cancerResponse rateSurvival rateNon-small cell lung cancerImmune checkpoint inhibitor antibodyCheckpoint inhibitor antibodyEfficacy of nivolumabPaclitaxel-carboplatin groupDose-limiting toxicityCurrent standard therapyWeeks of treatment
2015
Immune Checkpoint Modulation for Non–Small Cell Lung Cancer
Soria JC, Marabelle A, Brahmer JR, Gettinger S. Immune Checkpoint Modulation for Non–Small Cell Lung Cancer. Clinical Cancer Research 2015, 21: 2256-2262. PMID: 25979932, DOI: 10.1158/1078-0432.ccr-14-2959.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerAdvanced non-small cell lung cancerCell lung cancerImmune checkpointsL1 antibodyLung cancerClinical trialsT cellsImmune-related progression-free survivalCytotoxic T-lymphocyte-associated protein 4Response rateT-lymphocyte-associated protein 4Tumor PD-L1 expressionRandomized phase II trialImmune checkpoint modulationObjective response ratePD-L1 expressionPhase II trialProgression-free survivalDeath ligand 1Immunosuppressive T cellsAdditional clinical trialsLung cancer patientsLow toxicity profileNSCLC histology
2014
1229PD Smoking History and Response to Nivolumab in Patients with Advanced Nsclcs
Hellmann M, Creelan B, Woo K, Sima C, Iams W, Antonia S, Horn L, Brahmer J, Gettinger S, Harbison C, Rizvi N. 1229PD Smoking History and Response to Nivolumab in Patients with Advanced Nsclcs. Annals Of Oncology 2014, 25: iv429. DOI: 10.1093/annonc/mdu349.8.Peer-Reviewed Original ResearchBristol-Myers SquibbCurrent smokersSmoking historyAdvanced NSCLCResponse rateMutation burdenPD-1 pathway inhibitorsSelf-reported smoking historySubset of ptsHigh somatic mutation burdenLog-rank testSomatic mutation burdenKRAS MUTRECIST v1.0Squamous histologyObjective responseSmoking statusTobacco exposureKRAS genotypeLung cancerMutational burdenSmokersStratification factorsNSCLCNivolumab
2012
IS7-15 A Large Retrospective Analysis of the Activity of Pemetrexed (PEM) in Patients (Patients) with ALK+ NSCLC Before Crizotinib (CRIZ)
Scagliotti G, Kim D, Shaw A, Ou S, Riely G, Gettinger S, Besse B, Thomas M, Salgia R, Wilner K, Bartlett C, Polli A, Gandara D. IS7-15 A Large Retrospective Analysis of the Activity of Pemetrexed (PEM) in Patients (Patients) with ALK+ NSCLC Before Crizotinib (CRIZ). Annals Of Oncology 2012, 23: xi33. DOI: 10.1016/s0923-7534(20)32007-x.Peer-Reviewed Original ResearchObjective response rateMedian TTPPROFILE 1007Response rateLow objective response rateOngoing phase 3 trialsHigher objective response ratePhase 3 trialLarge retrospective analysisSingle-arm studySmall cohort studiesLarge phase 2High response rateAdenocarcinoma NSCLCBetter PFSCrossover patientsMedian PFSProgressive diseaseCohort studyNSCLC cohortRetrospective studyShorter TTPALK statusRetrospective analysisPemetrexedA large retrospective analysis of the activity of pemetrexed (PEM) in patients (pts) with ALK -positive ( ALK +) non-small cell lung cancer (NSCLC) prior to crizotinib (CRIZ).
Scagliotti G, Kim D, Shaw A, Ou S, Riely G, Gettinger S, Besse B, Thomas M, Salgia R, Wilner K, Bartlett C, Polli A, Gandara D. A large retrospective analysis of the activity of pemetrexed (PEM) in patients (pts) with ALK -positive ( ALK +) non-small cell lung cancer (NSCLC) prior to crizotinib (CRIZ). Journal Of Clinical Oncology 2012, 30: 7599-7599. DOI: 10.1200/jco.2012.30.15_suppl.7599.Peer-Reviewed Original ResearchNon-small cell lung cancerObjective response ratePROFILE 1007Median TTPAdenocarcinoma non-small cell lung cancerALK-positive non-small cell lung cancerResponse rateLow objective response rateOngoing phase 3 trialsHigher objective response ratePhase 3 trialSingle-arm studyLarge retrospective analysisCell lung cancerSmall cohort studiesLarge phase 2High response rateBetter PFSMedian PFSNSCLC cohortProgressive diseaseCohort studyRetrospective studyShorter TTPALK statusA randomized discontinuation phase II trial of ridaforolimus in non-small cell lung cancer (NSCLC) patients with KRAS mutations.
Riely G, Brahmer J, Planchard D, Crinò L, Doebele R, Mas Lopez L, Gettinger S, Schumann C, Li X, Atkins B, Ebbinghaus S, Rosell R. A randomized discontinuation phase II trial of ridaforolimus in non-small cell lung cancer (NSCLC) patients with KRAS mutations. Journal Of Clinical Oncology 2012, 30: 7531-7531. DOI: 10.1200/jco.2012.30.15_suppl.7531.Peer-Reviewed Original ResearchProgression-free survivalStable diseaseKRAS mutationsAdvanced NSCLCStage IIIB/IV non-small cell lung cancerResponse rateNon-small cell lung cancer patientsNon-small cell lung cancerMedian progression-free survivalProlonged progression-free survivalCell lung cancer patientsAvailable standard treatmentMucositis/stomatitisPhase II trialAdvanced endometrial cancerCell lung cancerLung cancer patientsOverall response rateSoft tissue sarcomasDays/week scheduleKRAS-mutant NSCLCInhibitor of mTORMedian OSOral ridaforolimusPrior chemotherapy
2009
Axitinib: The evidence of its potential in the treatment of advanced thyroid cancer
Deshpande HA, Gettinger S, Sosa JA. Axitinib: The evidence of its potential in the treatment of advanced thyroid cancer. Core Evidence 2009, Volume 4: 43-48. PMID: 20694064, PMCID: PMC2899774, DOI: 10.2147/ce.s5996.Peer-Reviewed Original ResearchThyroid cancerVascular endothelial growth factor receptor 1Common grade 3Refractory thyroid cancerUse of axitinibGood tolerability profilePhase II studyAdvanced thyroid cancerGrowth factor receptor 1Greater side effectsFactor receptor 1Growth factor receptorStable diseaseTolerability profileII studyHistological typeCancer deathGrade 3New small molecule inhibitorsRare diseaseSide effectsSmall molecule inhibitorsResponse rateNew treatmentsReceptor 1