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
2023
First-Line Treatment of Driver-Negative Non–Small Cell Lung Cancer
Kim S, Gettinger S. First-Line Treatment of Driver-Negative Non–Small Cell Lung Cancer. Hematology/Oncology Clinics Of North America 2023, 37: 557-573. PMID: 37150586, DOI: 10.1016/j.hoc.2023.02.008.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerLung cancerAdvanced non-small cell lung cancerFirst-line settingFirst-line treatmentStandard of careCombination immunotherapyImmunotherapy monotherapyPD-L1Immunotherapy responseLine treatmentSmoking statusTreatment choiceTrial dataCancerImmunotherapyRegimensCliniciansTreatmentChemoimmunotherapyMonotherapyCareNovel Approaches for Dynamic Visualization of Adverse Event Data in Oncology Clinical Trials: A Case Study Using Immunotherapy Trial S1400-I (SWOG).
Lee S, Fan W, Wang A, Vaidya R, Redman M, Gettinger S, Bazhenova L, Herbst R, Hershman D, Unger J. Novel Approaches for Dynamic Visualization of Adverse Event Data in Oncology Clinical Trials: A Case Study Using Immunotherapy Trial S1400-I (SWOG). JCO Clinical Cancer Informatics 2023, 7: e2200165. PMID: 37084329, PMCID: PMC10281446, DOI: 10.1200/cci.22.00165.Peer-Reviewed Original ResearchConceptsSystem organ classAdverse event dataRandomized phase III trialPhase III trialsCell lung cancerOncology clinical trialsOverall toxicity profileIII trialsNeurologic toxicityTreatment armsCardiac toxicityLung cancerClinical trialsGrade 3High prevalenceOrgan classToxicity profileNivolumabTreatment groupsStage IVEndocrine toxicityType of AEToxicity typesAE termsIpilimumabNCCN Guidelines® Insights: Non-Small Cell Lung Cancer, Version 2.2023.
Ettinger D, Wood D, Aisner D, Akerley W, Bauman J, Bharat A, Bruno D, Chang J, Chirieac L, DeCamp M, Dilling T, Dowell J, Durm G, Gettinger S, Grotz T, Gubens M, Hegde A, Lackner R, Lanuti M, Lin J, Loo B, Lovly C, Maldonado F, Massarelli E, Morgensztern D, Ng T, Otterson G, Patel S, Patil T, Polanco P, Riely G, Riess J, Schild S, Shapiro T, Singh A, Stevenson J, Tam A, Tanvetyanon T, Yanagawa J, Yang S, Yau E, Gregory K, Hughes M. NCCN Guidelines® Insights: Non-Small Cell Lung Cancer, Version 2.2023. Journal Of The National Comprehensive Cancer Network 2023, 21: 340-350. PMID: 37015337, DOI: 10.6004/jnccn.2023.0020.Peer-Reviewed Original ResearchSafety and clinical activity of atezolizumab plus erlotinib in patients with non-small-cell lung cancer
Rudin C, Cervantes A, Dowlati A, Besse B, Ma B, Costa D, Schmid P, Heist R, Villaflor V, Spahn J, Li S, Cha E, Riely G, Gettinger S. Safety and clinical activity of atezolizumab plus erlotinib in patients with non-small-cell lung cancer. ESMO Open 2023, 8: 101160. PMID: 36871392, PMCID: PMC10163154, DOI: 10.1016/j.esmoop.2023.101160.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsCell lung cancerAdverse eventsLung cancerClinical activityEpidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) efficacyGrade 3 treatment-related adverse eventsEGFR TKI-naive patientsMedian progression-free survivalEGFR mutation-positive NSCLCAdvanced EGFR mutation-positive NSCLCTyrosine kinase inhibitor efficacyDurable clinical activityTolerable safety profileMedian overall survivalMedian response durationObjective response ratePhase Ib trialSerious adverse eventsProgression-free survivalStage 2 patientsMutation-positive NSCLCEGFR-mutant NSCLCTKI-naive patientsAtezolizumab 1200Quality-of-life outcomes and risk prediction for patients randomized to nivolumab plus ipilimumab vs nivolumab on LungMAP-S1400I
Unger J, Qian L, Redman M, Tavernier S, Minasian L, Sigal E, Papadimitrakopoulou V, Leblanc M, Cleeland C, Dzingle S, Summers T, Chao H, Madhusudhana S, Villaruz L, Crawford J, Gray J, Kelly K, Gandara D, Bazhenova L, Herbst R, Gettinger S, Moinpour C. Quality-of-life outcomes and risk prediction for patients randomized to nivolumab plus ipilimumab vs nivolumab on LungMAP-S1400I. Journal Of The National Cancer Institute 2023, 115: 437-446. PMID: 36625510, PMCID: PMC10086628, DOI: 10.1093/jnci/djad003.Peer-Reviewed Original ResearchConceptsQuality of lifeComposite risk modelAppetite lossSeverity scoreWeek 13Advanced squamous cell lung cancerWeek 7Baseline patient-reported outcomesRandomized phase III trialSquamous cell lung cancerPhase III trialsRisk of progressionShortness of breathCell lung cancerPatient-reported outcomesRisk of deathMultivariable linear regressionEffect of treatmentEvaluable patientsPrimary endpointIII trialsOverall survivalMedian ageAdvanced cancerPrognostic relevance
2022
Non-Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.
Ettinger DS, Wood DE, Aisner DL, Akerley W, Bauman JR, Bharat A, Bruno DS, Chang JY, Chirieac LR, D'Amico TA, DeCamp M, Dilling TJ, Dowell J, Gettinger S, Grotz TE, Gubens MA, Hegde A, Lackner RP, Lanuti M, Lin J, Loo BW, Lovly CM, Maldonado F, Massarelli E, Morgensztern D, Ng T, Otterson GA, Pacheco JM, Patel SP, Riely GJ, Riess J, Schild SE, Shapiro TA, Singh AP, Stevenson J, Tam A, Tanvetyanon T, Yanagawa J, Yang SC, Yau E, Gregory K, Hughes M. Non-Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology. Journal Of The National Comprehensive Cancer Network 2022, 20: 497-530. PMID: 35545176, DOI: 10.6004/jnccn.2022.0025.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerNCCN Clinical Practice GuidelinesCell lung cancerClinical practice guidelinesLung cancerPractice guidelinesMetastatic non-small cell lung cancerMetastatic lung cancerNCCN guidelinesPrimary treatmentTargeted therapyActionable mutationsPatientsCancerSubsequent treatmentTherapyOncologyTreatmentGuidelinesImmunotherapyRelapseDiagnosisMicrowave Ablation versus Stereotactic Body Radiotherapy for Stage I Non–Small Cell Lung Cancer: A Cost-Effectiveness Analysis
Wu X, Uhlig J, Blasberg JD, Gettinger SN, Suh RD, Solomon SB, Kim HS. Microwave Ablation versus Stereotactic Body Radiotherapy for Stage I Non–Small Cell Lung Cancer: A Cost-Effectiveness Analysis. Journal Of Vascular And Interventional Radiology 2022, 33: 964-971.e2. PMID: 35490932, DOI: 10.1016/j.jvir.2022.04.019.Peer-Reviewed Original ResearchNivolumab Plus Ipilimumab for Previously Treated Stage IV Squamous Cell Lung Cancer—Reply
Gettinger S, Redman MW, Herbst RS. Nivolumab Plus Ipilimumab for Previously Treated Stage IV Squamous Cell Lung Cancer—Reply. JAMA Oncology 2022, 8: 1-1. PMID: 35142793, DOI: 10.1001/jamaoncol.2021.7790.Peer-Reviewed Original Research
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 NSCLCNTRK1 Fusions identified by non-invasive plasma next-generation sequencing (NGS) across 9 cancer types
Rolfo C, Drilon A, Hong D, McCoach C, Dowlati A, Lin JJ, Russo A, Schram AM, Liu SV, Nieva JJ, Nguyen T, Eshaghian S, Morse M, Gettinger S, Mobayed M, Goldberg S, Araujo-Mino E, Vidula N, Bardia A, Subramanian J, Sashital D, Stinchcombe T, Kiedrowski L, Price K, Gandara DR. NTRK1 Fusions identified by non-invasive plasma next-generation sequencing (NGS) across 9 cancer types. British Journal Of Cancer 2021, 126: 514-520. PMID: 34480094, PMCID: PMC8811064, DOI: 10.1038/s41416-021-01536-1.Peer-Reviewed Original ResearchConceptsPlasma next-generation sequencingNTRK1 fusionsTumor typesAdvanced-stage solid tumorsNTRK fusion-positive tumorsTarget resistance mechanismsTissue-based testingHigh positive predictive valuePrimary tumor typeIdentification of patientsNon-invasive screening methodNext-generation sequencingFusion-positive tumorsPositive predictive valueDurable responsesPediatric patientsNTRK fusionsDrivers of carcinogenesisClinical dataTRK inhibitorsClinical practiceCtDNA analysisPredictive valueSolid tumorsOncogenic driversClinical definition of acquired resistance to immunotherapy in patients with metastatic non-small-cell lung cancer
Schoenfeld A, Antonia S, Awad M, Felip E, Gainor J, Gettinger S, Hodi F, Johnson M, Leighl N, Lovly C, Mok T, Perol M, Reck M, Solomon B, Soria J, Tan D, Peters S, Hellmann M. Clinical definition of acquired resistance to immunotherapy in patients with metastatic non-small-cell lung cancer. Annals Of Oncology 2021, 32: 1597-1607. PMID: 34487855, DOI: 10.1016/j.annonc.2021.08.2151.Peer-Reviewed Original ResearchConceptsCell lung cancerClinical definitionAcquired ResistanceLung cancerClinical trialsCell death protein 1/Death protein 1/Consistent clinical definitionPersistent antitumor immunityProspective clinical trialsInvestigational immunotherapiesAntitumor immunityObjective responseProgressive diseaseAntibody treatmentNSCLC biologyInitial respondersTreatment strategiesClinical reportsPatientsBlockadeImmunotherapyTherapeutic discoveryCancerUniform criteriaNivolumab 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 survivalA Phase I Study of APX005M and Cabiralizumab with or without Nivolumab in Patients with Melanoma, Kidney Cancer, or Non–Small Cell Lung Cancer Resistant to Anti-PD-1/PD-L1
Weiss SA, Djureinovic D, Jessel S, Krykbaeva I, Zhang L, Jilaveanu L, Ralabate A, Johnson B, Levit NS, Anderson G, Zelterman D, Wei W, Mahajan A, Trifan O, Bosenberg M, Kaech SM, Perry CJ, Damsky W, Gettinger S, Sznol M, Hurwitz M, Kluger HM. A Phase I Study of APX005M and Cabiralizumab with or without Nivolumab in Patients with Melanoma, Kidney Cancer, or Non–Small Cell Lung Cancer Resistant to Anti-PD-1/PD-L1. Clinical Cancer Research 2021, 27: 4757-4767. PMID: 34140403, PMCID: PMC9236708, DOI: 10.1158/1078-0432.ccr-21-0903.Peer-Reviewed Original ResearchConceptsAnti-PD-1/PD-L1Non-small cell lung cancerCell lung cancerRenal cell carcinomaPD-L1Lung cancerDisease progressionCommon treatment-related adverse eventsPD-1/PD-L1 inhibitorsTreatment-related adverse eventsPhase 2 doseSubstantial clinical challengeUnconfirmed partial responseDose-limiting toxicityPD-L1 inhibitorsPhase I trialDose-escalation designPro-inflammatory cytokinesMultiple tumor typesAsymptomatic elevationStable diseaseIntolerable toxicityAdverse eventsMedian durationPartial responseClinical characteristics and outcomes of splenic infarction in cancer patients: a retrospective, single center report of 206 cases
Bewersdorf JP, Parmar N, Israel GM, Gettinger SN, Lee AI. Clinical characteristics and outcomes of splenic infarction in cancer patients: a retrospective, single center report of 206 cases. Journal Of Thrombosis And Thrombolysis 2021, 52: 854-862. PMID: 33765243, DOI: 10.1007/s11239-021-02428-0.Peer-Reviewed Original ResearchConceptsAtrial fibrillation/flutterSplenic infarctCancer patientsThromboembolic eventsRisk factorsHigh riskExact testMultivariable logistic regression modelYale-New Haven HospitalRetrospective cohort studyThromboembolic risk factorsUse of anticoagulationVenous thromboembolic eventsSingle-center reportsΧ2 testLow platelet countFisher's exact testNew Haven HospitalMultivariable regression modelsLow recurrence riskLogistic regression modelsPearson χ2 testAnticoagulation useClinical characteristicsCohort studyGenetic Determinants of EGFR-Driven Lung Cancer Growth and Therapeutic Response In VivoTumor Suppressor Genes and EGFR-Driven Lung Adenocarcinoma
Foggetti G, Li C, Cai H, Hellyer JA, Lin WY, Ayeni D, Hastings K, Choi J, Wurtz A, Andrejka L, Maghini DG, Rashleigh N, Levy S, Homer R, Gettinger SN, Diehn M, Wakelee HA, Petrov DA, Winslow MM, Politi K. Genetic Determinants of EGFR-Driven Lung Cancer Growth and Therapeutic Response In VivoTumor Suppressor Genes and EGFR-Driven Lung Adenocarcinoma. Cancer Discovery 2021, 11: 1736-1753. PMID: 33707235, PMCID: PMC8530463, DOI: 10.1158/2159-8290.cd-20-1385.Peer-Reviewed Original ResearchConceptsSuppressor geneKey tumor suppressorPutative tumor suppressor geneTumor suppressor geneSensitivity of EGFRTumor growthOncogenic contextTumor suppressorHuman EGFRGenetic determinantsKeap1 pathwayComplex genotypesTumor suppressor gene alterationsLung cancer growthGenesDeficient lung adenocarcinomaLung adenocarcinomaGenetic alterationsIssue featureStrong driverCancer growthEGFR inhibitorsKinase inhibitorsInactivationGene alterationsA Dose-finding Study Followed by a Phase II Randomized, Placebo-controlled Trial of Chemoradiotherapy With or Without Veliparib in Stage III Non–small-cell Lung Cancer: SWOG 1206 (8811)
Argiris A, Miao J, Cristea MC, Chen AM, Sands JM, Decker RH, Gettinger SN, Daly ME, Faller BA, Albain KS, Yanagihara RH, Garland LL, Byers LA, Wang D, Koczywas M, Redman MW, Kelly K, Gandara DR. A Dose-finding Study Followed by a Phase II Randomized, Placebo-controlled Trial of Chemoradiotherapy With or Without Veliparib in Stage III Non–small-cell Lung Cancer: SWOG 1206 (8811). Clinical Lung Cancer 2021, 22: 313-323.e1. PMID: 33745865, PMCID: PMC8562492, DOI: 10.1016/j.cllc.2021.02.009.Peer-Reviewed Original ResearchConceptsProgression-free survivalDose-limiting toxicityGrade 3 esophagitisPhase II partCell lung cancerLung cancerStage IIIPARP inhibitorsConcurrent weekly carboplatinEarly study closurePhase II RandomizedTrial of chemoradiotherapyDose-finding studyPhase I partStandard of careAdjuvant immunotherapyConsolidation carboplatinEligible patientsVeliparib doseWeekly carboplatinThoracic radiotherapyOverall survivalPlacebo armStudy closurePredictive biomarkersSecond-line nivolumab in relapsed small-cell lung cancer: CheckMate 331☆
Spigel D, Vicente D, Ciuleanu T, Gettinger S, Peters S, Horn L, Audigier-Valette C, Aranda N, Juan-Vidal O, Cheng Y, Zhang H, Shi M, Luft A, Wolf J, Antonia S, Nakagawa K, Fairchild J, Baudelet C, Pandya D, Doshi P, Chang H, Reck M. Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331☆. Annals Of Oncology 2021, 32: 631-641. PMID: 33539946, DOI: 10.1016/j.annonc.2021.01.071.Peer-Reviewed Original ResearchConceptsSmall cell lung cancerRelapsed Small-Cell Lung CancerOverall survivalLung cancerMedian progression-free survivalTreatment-related adverse eventsBaseline lactate dehydrogenaseBaseline liver metastasesSecond-line nivolumabSelect baseline characteristicsTrials of nivolumabImproved overall survivalObjective response rateCombined positive scoreNew safety signalsProgression-free survivalPlatinum-based chemotherapyPrimary endpointAdverse eventsBaseline characteristicsLiver metastasesMedian durationStandard chemotherapySurvival benefitUnacceptable toxicityFive-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 PSTumor DNA Mutations From Intraparenchymal Brain Metastases Are Detectable in CSF
Cheok SK, Narayan A, Arnal-Estape A, Gettinger S, Goldberg SB, Kluger HM, Nguyen D, Patel A, Chiang V. Tumor DNA Mutations From Intraparenchymal Brain Metastases Are Detectable in CSF. JCO Precision Oncology 2021, 5: 163-172. PMID: 34250381, PMCID: PMC8232069, DOI: 10.1200/po.20.00292.Peer-Reviewed Original ResearchConceptsIntraparenchymal brain metastasesBrain metastasesCell-free DNAExtracranial tumorsBrain metastasis tissuesProgressive brain metastasesThird of patientsNormal pressure hydrocephalusTumor DNA mutationsPrimary cancer typeAnalysis of CSFSamples of CSFLeptomeningeal diseaseEffective surrogate markerBrain biopsyPressure hydrocephalusLumbar punctureSurrogate markerCancer-associated genesMetastasis tissuesPatientsMetastasisDiscordant responsesRenal cellsGenomic profiling