2024
Phase II Trial of Afatinib in Patients With EGFR-Mutated Solid Tumors Excluding Lung Cancer: Results From NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol A
Gettinger S, Song Z, Reckamp K, Moscow J, Gray R, Wang V, McShane L, Rubinstein L, Patton D, Williams P, Hamilton S, Kong X, Tricoli J, Conley B, Arteaga C, Harris L, O'Dwyer P, Chen A, Flaherty K. Phase II Trial of Afatinib in Patients With EGFR-Mutated Solid Tumors Excluding Lung Cancer: Results From NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol A. JCO Precision Oncology 2024, 8: e2300725. PMID: 38986051, DOI: 10.1200/po.23.00725.Peer-Reviewed Original ResearchConceptsProgression-free survivalTyrosine kinase inhibitorsEGFR tyrosine kinase inhibitorsNCI-MATCHLung cancerGlioblastoma multiformeOverall survivalAdvanced non-small cell lung cancerNational Cancer Institute-Molecular AnalysisNon-small cell lung cancerEnd pointsTumor genomic testingTrial primary end pointPhase 2 trialPhase II trialSecondary end pointsPrimary end pointCell lung cancerCohort of patientsMedian OSStable diseaseAdenosquamous carcinomaProtocol therapyPartial responseArm A
2021
Brigatinib Versus Crizotinib in ALK Inhibitor–Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial
Camidge DR, Kim HR, Ahn MJ, Yang JCH, Han JY, Hochmair MJ, Lee KH, Delmonte A, Garcia Campelo MR, Kim DW, Griesinger F, Felip E, Califano R, Spira AI, Gettinger SN, Tiseo M, Lin HM, Liu Y, Vranceanu F, Niu H, Zhang P, Popat S. Brigatinib Versus Crizotinib in ALK Inhibitor–Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial. Journal Of Thoracic Oncology 2021, 16: 2091-2108. PMID: 34537440, DOI: 10.1016/j.jtho.2021.07.035.Peer-Reviewed Original ResearchConceptsBlinded independent review committeeIndependent review committeeBrain metastasesSurvival benefitSuperior efficacyTP53 mutationsAdvanced ALK-positive NSCLCBaseline brain metastasesSecondary ALK mutationsMedian overall survivalOverall survival benefitPrimary end pointNew safety signalsPhase 3 studyALK-positive NSCLCLung cancer trialsPlasma cell-free DNAPoor prognostic biomarkerReview CommitteeEML4-ALK variantsCell-free DNAAdvanced ALKOverall survivalPoor PFSPositive NSCLCNivolumab Plus Ipilimumab vs Nivolumab for Previously Treated Patients With Stage IV Squamous Cell Lung Cancer
Gettinger SN, Redman MW, Bazhenova L, Hirsch FR, Mack PC, Schwartz LH, Bradley JD, Stinchcombe TE, Leighl NB, Ramalingam SS, Tavernier SS, Yu H, Unger JM, Minichiello K, Highleyman L, Papadimitrakopoulou VA, Kelly K, Gandara DR, Herbst RS. Nivolumab Plus Ipilimumab vs Nivolumab for Previously Treated Patients With Stage IV Squamous Cell Lung Cancer. JAMA Oncology 2021, 7: 1368-1377. PMID: 34264316, PMCID: PMC8283667, DOI: 10.1001/jamaoncol.2021.2209.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerInvestigator-assessed progression-free survivalNivolumab/ipilimumabPlatinum-based chemotherapyCell lung cancerOverall survivalIpilimumab groupLung cancerClinical trialsDisease progressionStage IV squamous cell lung cancerAdvanced non-small cell lung cancerHigher treatment-related adverse eventsTreatment-related adverse eventsSquamous cell lung cancerNational Clinical Trials NetworkStandard platinum-based chemotherapyEnd pointAddition of ipilimumabIntolerable toxic effectsNivolumab Plus IpilimumabMedian response durationPrimary end pointSecondary end pointsProgression-free survivalFive-Year Outcomes From the Randomized, Phase III Trials CheckMate 017 and 057: Nivolumab Versus Docetaxel in Previously Treated Non–Small-Cell Lung Cancer
Borghaei H, Gettinger S, Vokes EE, Chow LQM, Burgio MA, de Castro Carpeno J, Pluzanski A, Arrieta O, Frontera OA, Chiari R, Butts C, Wójcik-Tomaszewska J, Coudert B, Garassino MC, Ready N, Felip E, García MA, Waterhouse D, Domine M, Barlesi F, Antonia S, Wohlleber M, Gerber DE, Czyzewicz G, Spigel DR, Crino L, Eberhardt WEE, Li A, Marimuthu S, Brahmer J. Five-Year Outcomes From the Randomized, Phase III Trials CheckMate 017 and 057: Nivolumab Versus Docetaxel in Previously Treated Non–Small-Cell Lung Cancer. Journal Of Clinical Oncology 2021, 39: 723-733. PMID: 33449799, PMCID: PMC8078445, DOI: 10.1200/jco.20.01605.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overCarcinoma, Non-Small-Cell LungClinical Trials, Phase III as TopicDisease ProgressionDocetaxelFemaleHumansImmune Checkpoint InhibitorsImmunotherapyLung NeoplasmsMaleMiddle AgedNivolumabProgression-Free SurvivalRandomized Controlled Trials as TopicTime FactorsTubulin ModulatorsYoung AdultConceptsTreatment-related adverse eventsNivolumab-treated patientsProgression-free survivalPhase III trialsOverall survivalCheckMate 017Advanced NSCLCIII trialsOS ratesLung cancerGrade 4 treatment-related adverse eventsFirst-line platinum-based chemotherapyNon-small cell lung cancerRandomized phase III trialEnd pointDeath-1 inhibitorsDocetaxel-treated patientsExploratory landmark analysisPrimary end pointSecondary end pointsFive-year outcomesNew safety signalsPlatinum-based chemotherapyCell lung cancerECOG PS
2020
Randomized Trial of Afatinib Plus Cetuximab Versus Afatinib Alone for First-Line Treatment of EGFR-Mutant Non-Small-Cell Lung Cancer: Final Results From SWOG S1403.
Goldberg SB, Redman MW, Lilenbaum R, Politi K, Stinchcombe TE, Horn L, Chen EH, Mashru SH, Gettinger SN, Melnick MA, Herbst RS, Baumgart MA, Miao J, Moon J, Kelly K, Gandara DR. Randomized Trial of Afatinib Plus Cetuximab Versus Afatinib Alone for First-Line Treatment of EGFR-Mutant Non-Small-Cell Lung Cancer: Final Results From SWOG S1403. Journal Of Clinical Oncology 2020, 38: 4076-4085. PMID: 33021871, PMCID: PMC7768342, DOI: 10.1200/jco.20.01149.Peer-Reviewed Original ResearchConceptsProgression-free survivalLung cancerMutant NSCLCEGFR monoclonal antibody cetuximabSmall cell lung cancerAddition of cetuximabPrimary end pointTyrosine kinase inhibitor afatinibCell lung cancerEGFR-Mutant NonCombination of afatinibMonoclonal antibody cetuximabAdvanced diseaseAdverse eventsOverall survivalMulticenter trialLine treatmentEGFR-TKIAntibody cetuximabDose reductionInhibitor afatinibInterim analysisCetuximabInsufficient evidencePatientsBrigatinib Versus Crizotinib in Advanced ALK Inhibitor–Naive ALK-Positive Non–Small Cell Lung Cancer: Second Interim Analysis of the Phase III ALTA-1L Trial
Camidge DR, Kim HR, Ahn MJ, Yang JCH, Han JY, Hochmair MJ, Lee KH, Delmonte A, Campelo M, Kim DW, Griesinger F, Felip E, Califano R, Spira A, Gettinger SN, Tiseo M, Lin HM, Gupta N, Hanley MJ, Ni Q, Zhang P, Popat S. Brigatinib Versus Crizotinib in Advanced ALK Inhibitor–Naive ALK-Positive Non–Small Cell Lung Cancer: Second Interim Analysis of the Phase III ALTA-1L Trial. Journal Of Clinical Oncology 2020, 38: 3592-3603. PMID: 32780660, PMCID: PMC7605398, DOI: 10.1200/jco.20.00505.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerALK-positive non-small cell lung cancerProgression-free survivalBlinded independent review committeeCell lung cancerInterim analysisLung cancerAdvanced ALK-positive non-small cell lung cancerGlobal health status/QoL scoreNext-generation anaplastic lymphoma kinase (ALK) inhibitorPositive non-small cell lung cancerPredictors of PFSPromising first-line treatmentSecond prespecified interim analysisSuperior progression-free survivalPlasma concentration-time curveAnaplastic lymphoma kinase inhibitorsPrespecified interim analysisPrimary end pointSecond interim analysisFirst-line treatmentFirst interim analysisHealth-related qualityIndependent review committeePatient-reported outcomes
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 brigatinib
2018
Brigatinib 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 groupExploratory 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 radiotherapyNivolumab 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 nivolumabSafety and feasibility of immuno-cryotherapy.
Raja J, Ghodadra A, Gettinger S, Kluger H, Sznol M, Schalper K, "Kevin" Kim H. Safety and feasibility of immuno-cryotherapy. Journal Of Clinical Oncology 2018, 36: 34-34. DOI: 10.1200/jco.2018.36.5_suppl.34.Peer-Reviewed Original ResearchAdverse eventsImage-guided cryotherapyGrade 3Metastatic non-small cell lung cancerNon-small cell lung cancerImmune checkpoint inhibitor resistanceImmune checkpoint inhibitor therapyAdverse Events criteriaCheckpoint inhibitor resistanceCheckpoint inhibitor therapyCTLA-4 blockadeDisease control rateHigher adverse eventsImmune checkpoint inhibitionPrimary end pointImmune checkpoint therapyCell lung cancerTypes of malignanciesCases of diarrheaProgression of diseaseSystemic immunotherapyMetastatic NSCLCPeriprocedural periodSecondary endpointsSite hematoma
2017
Phase II Trial of Atezolizumab As First-Line or Subsequent Therapy for Patients With Programmed Death-Ligand 1–Selected Advanced Non–Small-Cell Lung Cancer (BIRCH)
Peters S, Gettinger S, Johnson ML, Jänne PA, Garassino MC, Christoph D, Toh CK, Rizvi NA, Chaft JE, Carcereny Costa E, Patel JD, Chow LQM, Koczywas M, Ho C, Früh M, van den Heuvel M, Rothenstein J, Reck M, Paz-Ares L, Shepherd FA, Kurata T, Li Z, Qiu J, Kowanetz M, Mocci S, Shankar G, Sandler A, Felip E. Phase II Trial of Atezolizumab As First-Line or Subsequent Therapy for Patients With Programmed Death-Ligand 1–Selected Advanced Non–Small-Cell Lung Cancer (BIRCH). Journal Of Clinical Oncology 2017, 35: jco.2016.71.947. PMID: 28609226, PMCID: PMC5562171, DOI: 10.1200/jco.2016.71.9476.Peer-Reviewed Original ResearchConceptsMedian overall survivalOverall survivalImmune cellsPD-L1Tumor cellsLung cancerAdvanced non-small cell lung cancerNon-small cell lung cancerTumor-infiltrating immune cellsEnd pointEfficacy of atezolizumabEfficacy-evaluable patientsMethods Eligible patientsObjective response ratePrimary end pointSecondary end pointsLines of therapyPD-L1 expressionPD-L1 statusPhase II trialProgression-free survivalDeath ligand 1Cell lung cancerKRAS mutation statusAtezolizumab monotherapyBrigatinib 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
The BATTLE-2 Study: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non–Small-Cell Lung Cancer
Papadimitrakopoulou V, Lee JJ, Wistuba II, Tsao AS, Fossella FV, Kalhor N, Gupta S, Byers LA, Izzo JG, Gettinger SN, Goldberg SB, Tang X, Miller VA, Skoulidis F, Gibbons DL, Shen L, Wei C, Diao L, Peng SA, Wang J, Tam AL, Coombes KR, Koo JS, Mauro DJ, Rubin EH, Heymach JV, Hong WK, Herbst RS. The BATTLE-2 Study: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non–Small-Cell Lung Cancer. Journal Of Clinical Oncology 2016, 34: 3638-3647. PMID: 27480147, PMCID: PMC5065110, DOI: 10.1200/jco.2015.66.0084.Peer-Reviewed Original ResearchDisease control rateKRAS wild-type patientsMedian overall survivalProgression-free survivalWild-type patientsArm 1Overall survivalKRAS statusArm 3Lung cancerAdvanced non-small cell lung cancerNon-small cell lung cancerBiomarker-driven treatment strategiesLung Cancer Elimination (BATTLE) trialMedian progression-free survivalImproved progression-free survivalBiomarker-Integrated ApproachesReal-time biopsyPrimary end pointCell lung cancerPrior therapyUmbrella studyAdvanced NSCLCControl rateMesenchymal tumors
2015
Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer
Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhäufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crinò L, Blumenschein GR, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR. Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer. New England Journal Of Medicine 2015, 373: 1627-1639. PMID: 26412456, PMCID: PMC5705936, DOI: 10.1056/nejmoa1507643.Peer-Reviewed Original ResearchConceptsProgression-free survivalOverall survival rateOverall survivalNivolumab groupDocetaxel groupLung cancerAdvanced nonsquamous non-small cell lung cancerNonsquamous non-small cell lung cancerSurvival rateNon-small cell lung cancerInternational phase 3 studyPD-1-mediated signalingPlatinum-based doublet chemotherapyTreatment-related adverse eventsEnd pointAdvanced nonsquamous NSCLCMedian overall survivalPrimary end pointPD-1 ligandsPhase 3 studyPlatinum-based chemotherapyCell lung cancerBody surface areaDoublet chemotherapyNonsquamous NSCLC