2024
EP.07C.10 Real-World Outcomes of Patients Treated with Neoadjuvant Immunotherapy for Resectable Non-Small Cell Lung Cancer
Ermer T, Kim S, Goldberg S, Zolfaghari E, Blasberg J, Boffa D, Herbst R, Politi K, Schalper K, Dacic S, Woodard G. EP.07C.10 Real-World Outcomes of Patients Treated with Neoadjuvant Immunotherapy for Resectable Non-Small Cell Lung Cancer. Journal Of Thoracic Oncology 2024, 19: s543-s544. DOI: 10.1016/j.jtho.2024.09.1007.Peer-Reviewed Original ResearchAuthor Correction: Mechanisms and clinical activity of an EGFR and HER2 exon 20–selective kinase inhibitor in non–small cell lung cancer
Robichaux J, Elamin Y, Tan Z, Carter B, Zhang S, Liu S, Li S, Chen T, Poteete A, Estrada-Bernal A, Le A, Truini A, Nilsson M, Sun H, Roarty E, Goldberg S, Brahmer J, Altan M, Lu C, Papadimitrakopoulou V, Politi K, Doebele R, Wong K, Heymach J. Author Correction: Mechanisms and clinical activity of an EGFR and HER2 exon 20–selective kinase inhibitor in non–small cell lung cancer. Nature Medicine 2024, 30: 2694-2695. PMID: 39164519, DOI: 10.1038/s41591-024-03178-1.Peer-Reviewed Original ResearchBSLM-10 MOLECULAR AND HISTOLOGICAL CHARACTERIZATION OF NSCLC PROGRESSION TO LEPTOMENINGEAL METASTASIS WITH COMORBID INTRAPARENCHYMAL DISEASE
Kandigian S, Chande S, Dolezal D, Tang T, Wang D, Arnal-Estapé A, Cheok S, McGuone D, Liu Y, Goldberg S, Blondin N, Chiang V, Nguyen D. BSLM-10 MOLECULAR AND HISTOLOGICAL CHARACTERIZATION OF NSCLC PROGRESSION TO LEPTOMENINGEAL METASTASIS WITH COMORBID INTRAPARENCHYMAL DISEASE. Neuro-Oncology Advances 2024, 6: i7-i7. PMCID: PMC11296776, DOI: 10.1093/noajnl/vdae090.020.Peer-Reviewed Original ResearchNon-small cell lung cancerLeptomeningeal diseaseCentral nervous systemLeptomeningeal metastasesParenchymal metastasesCerebrospinal fluidTumor cellsTyrosine kinase inhibitor treatmentCell lung cancerKinase inhibitor treatmentCerebrospinal fluid of patientsCell linesCerebral lateral ventriclesIntra-arterial injectionTGF-b signalingIn vivo passageIntraparenchymal diseaseMechanisms of progressionTumor microenvironmentMultiplex immunofluorescenceAggressive treatmentLeptomeningeal infiltrationPerivascular invasionIntraparenchymal metastasesMurine modelCentral nervous system metastases in advanced non-small cell lung cancer: A review of the therapeutic landscape
Weller M, Remon J, Rieken S, Vollmuth P, Ahn M, Minniti G, Le Rhun E, Westphal M, Brastianos P, Soo R, Kirkpatrick J, Goldberg S, Öhrling K, Hegi-Johnson F, Hendriks L. Central nervous system metastases in advanced non-small cell lung cancer: A review of the therapeutic landscape. Cancer Treatment Reviews 2024, 130: 102807. PMID: 39151281, DOI: 10.1016/j.ctrv.2024.102807.Peer-Reviewed Original ResearchNon-small cell lung cancerAdvanced non-small cell lung cancerCentral nervous system metastasesCentral nervous systemCell lung cancerOncogene-addicted non-small cell lung cancerLung cancerAssessment of treatment responseProgressive CNS metastasesImmune checkpoint inhibitorsNervous system metastasesLocal treatment optionsMultimodal therapeutic strategiesCNS diseaseSubgroup of patientsTreatment of patientsCheckpoint inhibitorsCNS metastasesLung cancer clinical trialsSystemic metastasesLocal therapySystemic therapyIntracranial activityTargeted therapyTreatment optionsTyrosine Kinase Inhibitors With and Without Up-Front Stereotactic Radiosurgery for Brain Metastases From EGFR and ALK Oncogene–Driven Non–Small Cell Lung Cancer (TURBO-NSCLC)
Pike L, Miao E, Boe L, Patil T, Imber B, Myall N, Pollom E, Hui C, Qu V, Langston J, Chiang V, Grant M, Goldberg S, Palmer J, Prasad R, Wang T, Lee A, Shu C, Chen L, Thomas N, Braunstein S, Kavanagh B, Camidge D, Rusthoven C. Tyrosine Kinase Inhibitors With and Without Up-Front Stereotactic Radiosurgery for Brain Metastases From EGFR and ALK Oncogene–Driven Non–Small Cell Lung Cancer (TURBO-NSCLC). Journal Of Clinical Oncology 2024, 42: 3606-3617. PMID: 39047224, DOI: 10.1200/jco.23.02668.Peer-Reviewed Original ResearchNon-small cell lung cancerUp-front stereotactic radiosurgeryTyrosine kinase inhibitorsALK-driven NSCLCStereotactic radiosurgeryBrain metastasesCell lung cancerOverall survivalCNS controlLung cancerOncogene-driven non-small cell lung cancerKinase inhibitorsCNS progression-free survivalStereotactic radiosurgery groupTKI-naive patientsProgression-free survivalAnaplastic lymphoma kinaseEpidermal growth factor receptorCox proportional hazards modelsGrowth factor receptorClinically relevant factorsProportional hazards modelMedian OSNo significant differenceNeurological symptomsPACIFIC-9: Phase III trial of durvalumab + oleclumab or monalizumab in unresectable stage III non-small-cell lung cancer
Barlesi F, Cho B, Goldberg S, Yoh K, Gelatti A, Mann H, Gopinathan A, Bielecka Z, Newton M, Aggarwal C. PACIFIC-9: Phase III trial of durvalumab + oleclumab or monalizumab in unresectable stage III non-small-cell lung cancer. Future Oncology 2024, 20: 2137-2147. PMID: 39023287, PMCID: PMC11508940, DOI: 10.1080/14796694.2024.2354160.Peer-Reviewed Original ResearchNon-small-cell lung cancerStage III non-small-cell lung cancerIII non-small-cell lung cancerPhase III trialsConcurrent chemoradiotherapyUnresectable stage III non-small-cell lung cancerLung cancerPhase III PACIFIC trialGlobal standard of careTargeting PD-L1Early-phase trialsStandard of carePACIFIC trialPD-L1Double-blindIII trialsPlacebo-controlledDurvalumabMonalizumabOleclumabDisease progressionAntitumor activityMonoclonal antibodiesImmunotherapyMAbTyrosine kinase inhibitors with and without upfront CNS radiation for brain metastases in oncogene-driven non-small cell lung cancer (TURBO-NSCLC).
Miao E, Pike L, Boe L, Patil T, Myall N, Hui C, Pollom E, Qu V, Langston J, Grant M, Goldberg S, Palmer J, Prasad R, Wang T, Lee A, Shu C, Chen L, Thomas N, Camidge D, Rusthoven C. Tyrosine kinase inhibitors with and without upfront CNS radiation for brain metastases in oncogene-driven non-small cell lung cancer (TURBO-NSCLC). Journal Of Clinical Oncology 2024, 42: 2019-2019. DOI: 10.1200/jco.2024.42.16_suppl.2019.Peer-Reviewed Original ResearchTyrosine kinase inhibitorsUpfront stereotactic radiosurgeryCentral nervous systemTKI-naive patientsStereotactic radiosurgeryOverall survivalMultivariable adjustmentCNS controlNeurological symptomsCNS objective response rateOncogene-driven non-small cell lung cancerFirst-generation TKIsKinase inhibitorsUpfront tyrosine kinase inhibitorNon-small cell lung cancerCentral nervous system radiationGeneration tyrosine kinase inhibitorsEGFR-mutant NSCLCMulti-institutional seriesObjective response rateInferior overall survivalMedian follow-upTreatment of BMCell lung cancerCox proportional hazards modelsComprehensive characterization of ERBB2 genomic alterations inlung cancer.
El Zarif T, Stockhammer P, Schillo J, Goldberg S, Politi K, Grant M. Comprehensive characterization of ERBB2 genomic alterations inlung cancer. Journal Of Clinical Oncology 2024, 42: 3148-3148. DOI: 10.1200/jco.2024.42.16_suppl.3148.Peer-Reviewed Original ResearchNon-small cell lung cancerProgression-free survivalShorter progression-free survivalTyrosine kinase domainSystemic therapyCo-mutationsClinical characteristics of non-small cell lung cancerCharacteristics of non-small cell lung cancerFirst-line platinum-based chemotherapyMedian tumor mutation burdenNon-small cell lung cancer tumorsFirst-line systemic therapyTP53 co-mutationsPlatinum-based chemotherapyTumor mutational burdenKaplan-Meier methodCell lung cancerLog-rank testOptimal treatment strategyHistory of smokingCopy number profilesTumor profile dataJuxtamembrane domainSquamous histologyTrastuzumab deruxtecanHLA class-I antigen presentation machinery (APM) alterations mediate immune evasion in lung cancer brain metastases.
Vilariño N, Lopez De Rodas M, Ranjan K, Costantini A, Villalba M, Lu B, Kravitz C, Nadal E, Goldberg S, Nguyen D, Schalper K. HLA class-I antigen presentation machinery (APM) alterations mediate immune evasion in lung cancer brain metastases. Journal Of Clinical Oncology 2024, 42: e14014-e14014. DOI: 10.1200/jco.2024.42.16_suppl.e14014.Peer-Reviewed Original ResearchLung cancer brain metastasisPrimary lung tumorsTumor-infiltrating lymphocytesImmune checkpoint inhibitorsCancer brain metastasesAntigen presentation machineryB2M expressionIFN-gBrain metastasesB2MImmune evasionAssociated with shorter overall survivalMultiplexed quantitative immunofluorescenceM expressionExpression of B2MB2M levelsExpression of pSTAT1Shorter overall survivalUnfavorable clinical featuresNo significant associationAssociated with unfavorable clinical featuresCheckpoint inhibitorsImmunotherapy resistanceProperties of tumorsPresentation machinery
2023
1102 The HLA-E/NKG2A axis is a dominant immunomodulatory pathway associated with distinct tumor microenvironment features in a subset of NSCLC
Ashley K, Iyer K, Kumar R, Cooper Z, Herbst R, Goldberg S, Schalper K. 1102 The HLA-E/NKG2A axis is a dominant immunomodulatory pathway associated with distinct tumor microenvironment features in a subset of NSCLC. 2023, a1213-a1213. DOI: 10.1136/jitc-2023-sitc2023.1102.Peer-Reviewed Original Research1103 Spatial mapping and clinical significance of the CD39/CD73 adenosinergic pathway as a candidate immunotherapy target in non-small cell lung cancer
Ashley K, Iyer K, Kumar R, Cooper Z, Herbst R, Goldberg S, Schalper K. 1103 Spatial mapping and clinical significance of the CD39/CD73 adenosinergic pathway as a candidate immunotherapy target in non-small cell lung cancer. 2023, a1214-a1214. DOI: 10.1136/jitc-2023-sitc2023.1103.Peer-Reviewed Original ResearchMA15.07 NC318, an Anti-Siglec-15 Humanized mAb, Alone and in Combination with Pembrolizumab in Immunotherapy Pretreated NSCLC
Gettinger S, Goldberg S, Chiang A, Wilson F, Kim S, Rowen E, Gerrish H, Duffield E, Davies M, Dest V, Jackson R, Pope J, Myint H, Langermann S, Cheng W, Rimm D, Chen L, Herbst R. MA15.07 NC318, an Anti-Siglec-15 Humanized mAb, Alone and in Combination with Pembrolizumab in Immunotherapy Pretreated NSCLC. Journal Of Thoracic Oncology 2023, 18: s155. DOI: 10.1016/j.jtho.2023.09.224.Peer-Reviewed Original ResearchCo-Occurring Alterations in Multiple Tumor Suppressor Genes Are Associated With Worse Outcomes in Patients With EGFR-Mutant Lung Cancer
Stockhammer P, Grant M, Wurtz A, Foggetti G, Expósito F, Gu J, Zhao H, Choi J, Chung S, Li F, Walther Z, Dietz J, Duffield E, Gettinger S, Politi K, Goldberg S. Co-Occurring Alterations in Multiple Tumor Suppressor Genes Are Associated With Worse Outcomes in Patients With EGFR-Mutant Lung Cancer. Journal Of Thoracic Oncology 2023, 19: 240-251. PMID: 37806385, PMCID: PMC11364167, DOI: 10.1016/j.jtho.2023.10.001.Peer-Reviewed Original ResearchProgression-free survivalEGFR-mutant NSCLCTP53 mutationsOverall survivalClinical outcomesEGFR-TKIInferior outcomesWorse outcomesYale cohortMetastatic EGFR-mutant NSCLCShorter progression-free survivalEGFR-mutant lung cancerTyrosine kinase inhibitor therapyFirst-line TKIYale Cancer CenterSecond-line therapyInferior clinical outcomesSubset of patientsKinase inhibitor therapyAdditional therapeutic interventionsAggressive disease phenotypeCo-occurring alterationsTumor suppressor gene alterationsTumor genomic profilingMultiple tumor suppressor genesBSBM-16 HLA CLASS-I ANTIGEN PRESENTATION MACHINERY AND IFN-γ PATHWAY ALTERATIONS IN LUNG CANCER BRAIN METASTASES
Vilarino N, de Rodas M, Lu B, Goldberg S, Schalper K. BSBM-16 HLA CLASS-I ANTIGEN PRESENTATION MACHINERY AND IFN-γ PATHWAY ALTERATIONS IN LUNG CANCER BRAIN METASTASES. Neuro-Oncology Advances 2023, 5: iii4-iii4. PMCID: PMC10402438, DOI: 10.1093/noajnl/vdad070.012.Peer-Reviewed Original ResearchLung cancer brain metastasesPrimary lung tumorsImmune checkpoint inhibitorsCancer brain metastasesBrain metastasesPresentation machineryClinicopathologic variablesHLA classTumor cell PD-L1 expressionBackground Immune checkpoint inhibitorsLocal adaptive immune responseHLA Class I AntigenPD-L1 expressionDuration of responseB2MAdaptive immune responsesDistinct immunomodulatory propertiesImmune evasion mechanismsClass I AntigenIFN-γ signalingIRF-1Interferon regulatory factor 1Checkpoint inhibitorsMost patientsWorse survivalPrecise, pragmatic and inclusive: the modern era of oncology clinical trials
Grant M, Goldberg S. Precise, pragmatic and inclusive: the modern era of oncology clinical trials. Nature Medicine 2023, 29: 1908-1909. PMID: 37524954, DOI: 10.1038/s41591-023-02466-6.Peer-Reviewed Original ResearchEGFR tyrosine kinase inhibitors (TKIs) versus durvalumab (durva) following concurrent chemoradiation (CRT) in unresectable EGFR-mutant non-small-cell lung cancer (NSCLC).
Nassar A, Adib E, Feng J, Aredo J, Parikh K, Harris J, Velazquez Manana A, Ragavan M, Lin J, Piotrowska Z, Fitzgerald B, Grohé C, Sankar K, Neal J, Wakelee H, Shepherd F, Herbst R, Naqash A, Goldberg S, Kim S. EGFR tyrosine kinase inhibitors (TKIs) versus durvalumab (durva) following concurrent chemoradiation (CRT) in unresectable EGFR-mutant non-small-cell lung cancer (NSCLC). Journal Of Clinical Oncology 2023, 41: 8567-8567. DOI: 10.1200/jco.2023.41.16_suppl.8567.Peer-Reviewed Original ResearchEGFR tyrosine kinase inhibitorsDisease-free survivalTyrosine kinase inhibitorsTreatment-related adverse eventsConcurrent chemoradiationOverall survivalStage IIILonger disease-free survivalMulti-institutional retrospective analysisDefinitive radiation therapyPD-L1 expressionPD-L1 statusDefinitive concurrent chemoradiationEGFR-TKI therapyPlatinum-based chemotherapyCell lung cancerEGFR-mutant NSCLCGy of radiationAdjuvant osimertinibCTCAE 5.0PACIFIC trialAdvanced NSCLCConcurrent chemotherapyBaseline characteristicsMedian durationPhase 3 study of durvalumab combined with oleclumab or monalizumab in patients with unresectable stage III NSCLC (PACIFIC-9).
Barlesi F, Goldberg S, Mann H, Gopinathan A, Newton M, Aggarwal C. Phase 3 study of durvalumab combined with oleclumab or monalizumab in patients with unresectable stage III NSCLC (PACIFIC-9). Journal Of Clinical Oncology 2023, 41: tps8610-tps8610. DOI: 10.1200/jco.2023.41.16_suppl.tps8610.Peer-Reviewed Original ResearchUnresectable stage III NSCLCStage III NSCLCBlinded independent central reviewProgression-free survivalIII NSCLCConsolidation therapyNumerically higher objective response rateBind to HLA-EHigher objective response rateInhibition of natural killerProlonged progression-free survivalCD8+ T cellsResponse rateDurvalumab consolidation therapyObjective response ratePD-L1 expressionPD-L1 statusPD-L1 inhibitionPromote antitumor immunityDuration of responsePhase 2 trialWHO performance statusIndependent central reviewPhase 3 studyMonths of treatmentBrief Report: Safety and Antitumor Activity of Durvalumab Plus Tremelimumab in Programmed Cell Death-(Ligand)1–Monotherapy Pretreated, Advanced NSCLC: Results From a Phase 1b Clinical Trial
Garon E, Spira A, Goldberg S, Chaft J, Papadimitrakopoulou V, Cascone T, Antonia S, Brahmer J, Camidge D, Powderly J, Wozniak A, Felip E, Wu S, Ascierto M, Elgeioushi N, Awad M. Brief Report: Safety and Antitumor Activity of Durvalumab Plus Tremelimumab in Programmed Cell Death-(Ligand)1–Monotherapy Pretreated, Advanced NSCLC: Results From a Phase 1b Clinical Trial. Journal Of Thoracic Oncology 2023, 18: 1094-1102. PMID: 37146752, DOI: 10.1016/j.jtho.2023.04.020.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerObjective response rateAdvanced non-small cell lung cancerTreatment-related adverse eventsBlinded independent central reviewIndependent central reviewRECIST v1.1Refractory patientsAdverse eventsCentral reviewRefractory non-small cell lung cancerCommon treatment-related adverse eventsSolid Tumors version 1.1Cell death protein 1End pointPhase 1b clinical trialEfficacy of durvalumabPhase 1b studyManageable safety profilePrimary end pointSecondary end pointsProgression-free survivalResponse Evaluation CriteriaMonths of treatmentDeath protein 1The Evolving Role for Systemic Therapy in Resectable Non-small Cell Lung Cancer
Grant M, Woodard G, Goldberg S. The Evolving Role for Systemic Therapy in Resectable Non-small Cell Lung Cancer. Hematology/Oncology Clinics Of North America 2023, 37: 513-531. PMID: 37024389, DOI: 10.1016/j.hoc.2023.02.003.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerLung cancerMetastatic non-small cell lung cancerResectable non-small cell lung cancerImmuno-oncology agentsHistologic classification systemUnited States FoodResectable tumorsSystemic therapyDriver alterationsDrug AdministrationStates FoodSystemic managementPatientsTherapyCancerEvolving roleClassification systemNTRKHER2TumorsKRASEGFRBRAFSociety for Immunotherapy of Cancer (SITC) consensus definitions for resistance to combinations of immune checkpoint inhibitors with chemotherapy
Rizvi N, Ademuyiwa F, Cao Z, Chen H, Ferris R, Goldberg S, Hellmann M, Mehra R, Rhee I, Park J, Kluger H, Tawbi H, Sullivan R. Society for Immunotherapy of Cancer (SITC) consensus definitions for resistance to combinations of immune checkpoint inhibitors with chemotherapy. Journal For ImmunoTherapy Of Cancer 2023, 11: e005920. PMID: 36918220, PMCID: PMC10016262, DOI: 10.1136/jitc-2022-005920.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsConsensus definitionCheckpoint inhibitorsAddition of ICIsAnti-programmed cell death protein 1Combination of ICIsCell death protein 1Consensus clinical definitionProfound clinical benefitDeath protein 1Immunotherapy of cancerSolid tumor indicationsClinical trial designICI combinationsImmunotherapy combinationsRecurrent diseaseUpfront treatmentClinical benefitLung cancerMechanisms of resistanceTargeted therapyClinical definitionTumor indicationsTrial designUS Food