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 1200
2022
2MO First-line (1L) nivolumab (NIVO) + ipilimumab (IPI) in metastatic non-small cell lung cancer (mNSCLC): Clinical outcomes and biomarker analyses from CheckMate 592
Gettinger S, Schenker M, De Langen J, Fischer J, Morgensztern D, Ciuleanu T, Beck T, De Castro Carpeno J, Schumann C, Yang X, Telivala B, Deschepper K, Nadal E, Schalper K, Spires T, Balli D, Nassar A, Karam S, Bhingare A, Spigel D. 2MO First-line (1L) nivolumab (NIVO) + ipilimumab (IPI) in metastatic non-small cell lung cancer (mNSCLC): Clinical outcomes and biomarker analyses from CheckMate 592. Immuno-Oncology Technology 2022, 16: 100107. DOI: 10.1016/j.iotech.2022.100107.Peer-Reviewed Original Research235 (PB115) Phase II trial of afatinib in patients with EGFR-mutated solid tumors excluding lung cancer: results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol A
Reckamp K, Song Z, Gettinger S, Mitchell E, Wright J, Moscow J, Gray R, Wang V, McShane L, Rubinstein L, Patton D, Williams P, Hamilton S, Conley B, Arteaga C, Harris L, O’Dwyer P, Chen A, Flaherty K. 235 (PB115) Phase II trial of afatinib in patients with EGFR-mutated solid tumors excluding lung cancer: results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol A. European Journal Of Cancer 2022, 174: s84-s85. DOI: 10.1016/s0959-8049(22)01023-1.Peer-Reviewed Original ResearchDynamic changes in serum analyte levels associated with clinical outcome in squamous cell lung cancer trial SWOG Lung-MAP S1400I of nivolumab ± ipilimumab.
Gonzalez-Kozlova E, Huang H, Redman M, Herbst R, Gettinger S, Bazhenova L, Xie H, Patel M, Nie K, Harris J, Argueta K, Cerami E, Hong J, Biswas R, Van Nostrand S, Kelly K, Moravec R, Del Valle D, Kim-Schulze S, Gnjatic S. Dynamic changes in serum analyte levels associated with clinical outcome in squamous cell lung cancer trial SWOG Lung-MAP S1400I of nivolumab ± ipilimumab. Journal Of Clinical Oncology 2022, 40: 9044-9044. DOI: 10.1200/jco.2022.40.16_suppl.9044.Peer-Reviewed Original ResearchImmune checkpoint blockadeSerial blood specimensObjective responseOverall survivalLung cancerBlood specimensCox modelRecurrent squamous cell lung cancerWk 3Randomized phase III trialSquamous cell lung cancerPhase III trialsBest objective responseCell lung cancerRisk of deathProtein levelsSerum analyte levelsIndicators of outcomeLinear mixed modelsSerum protein levelsProximity extension assayMeasurement of bloodEligible patientsLower IL6Checkpoint blockadeMultiomics profiling and association with molecular and immune features in association with benefits from immunotherapy for patients with previously treated stage IV or recurrent squamous cell lung cancer from the phase III SWOG LungMAP S1400I trial.
Parra E, Duose D, Zhang J, Redman M, Segura R, Marques-Piubelli M, Fernandez C, Zhang B, Lindsay J, Moravec R, Kannan K, Luthra R, Alatrash G, Herbst R, Wistuba I, Gettinger S, Bazhenova L, Lee J, Zhang J, Haymaker C. Multiomics profiling and association with molecular and immune features in association with benefits from immunotherapy for patients with previously treated stage IV or recurrent squamous cell lung cancer from the phase III SWOG LungMAP S1400I trial. Journal Of Clinical Oncology 2022, 40: 9046-9046. DOI: 10.1200/jco.2022.40.16_suppl.9046.Peer-Reviewed Original ResearchImmune checkpoint blockadeSquamous cell carcinomaT cellsBetter PFSLung cancerRecurrent squamous cell lung cancerTumor compartmentsLog-rank test analysisMetastatic lung squamous cell carcinomaSquamous cell lung cancerPD-1/CTLALung squamous cell carcinomaImmune cell scoreSingle-agent nivolumabDurable clinical benefitCD8 T cellsCell lung cancerCytotoxic immune cellsPositive clinical outcomesCell phenotypeFFPE tumor tissueBetter OSEligible patientsImmunogenomic profilingWorse OSNon-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 treatmentTherapyOncologyTreatmentGuidelinesImmunotherapyRelapseDiagnosis29P Brigatinib (BRG) vs crizotinib (CRZ) in anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor-naive ALK+ non-small cell lung cancer (NSCLC): ALTA-1L final results
Tiseo M, Popat S, Kim H, Ahn M, Yang J, Han J, Hochmair M, Lee K, Delmonte A, Campelo M, Kim D, Griesinger F, Felip E, Califano R, Spira A, Gettinger S, Lin H, Liu Y, Vranceanu F, Camidge D. 29P Brigatinib (BRG) vs crizotinib (CRZ) in anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor-naive ALK+ non-small cell lung cancer (NSCLC): ALTA-1L final results. Annals Of Oncology 2022, 33: s44-s45. DOI: 10.1016/j.annonc.2022.02.038.Peer-Reviewed Original Research
2021
Immune Therapy: What Can We Learn From Acquired Resistance?
Grant M, Politi K, Gettinger S. Immune Therapy: What Can We Learn From Acquired Resistance? Current Cancer Research 2021, 75-114. DOI: 10.1007/978-3-030-74028-3_5.ChaptersNon-small cell lung cancerAdvanced non-small cell lung cancerDeath-1 pathway inhibitorsPD-1 axis inhibitorsInitial tumor regressionCell lung cancerImmune checkpoint pathwaysIFN-γ signalingMediators of resistanceDisease stabilitySystemic progressionMost patientsLocal therapyClinical criteriaLung cancerTumor regressionTumor typesDisease sitesPathway inhibitorAcquired ResistancePresentation defectPatientsTranslational workProgressionEpigenetic changesClinical 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 responseA 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 toxicityProlonged Complete Response of Early Stage Primary Adenocarcinoma of the Lung to Nivolumab Monotherapy.
Unlu S, Grant MJ, Gettinger S, Adeniran A, Kluger HM. Prolonged Complete Response of Early Stage Primary Adenocarcinoma of the Lung to Nivolumab Monotherapy. Clinical Oncology Case Reports 2021, 4 PMID: 34382032, PMCID: PMC8353529.Peer-Reviewed Original ResearchMultiple primary malignant tumorsNivolumab monotherapyCheckpoint inhibitorsLung cancerHigh Programmed-Death Ligand 1 (PD-L1) expressionProgrammed Death Ligand 1 ExpressionNon-small cell lung cancerMultiple regional lymph nodesImmune checkpoint inhibitorsPD-1 inhibitorsLigand 1 expressionPrimary lung cancerEarly-stage diseaseRegional lymph nodesCell lung cancerPrimary malignant tumorsHigh-risk natureSystemic immunotherapyDurable responsesAdvanced melanomaComplete responseEffective immunotherapyLymph nodesMore patientsPrimary adenocarcinomaFive-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 evidencePatients