2024
Tyrosine 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, 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 durationBrief 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 FoodEfficacy of Osimertinib in Patients with Lung Cancer Positive for Uncommon EGFR Exon 19 Deletion Mutations
Grant M, Aredo J, Starrett J, Stockhammer P, van Rosenburgh I, Wurtz A, Piper-Valillo A, Piotrowska Z, Falcon C, Yu H, Aggarwal C, Scholes D, Patil T, Nguyen C, Phadke M, Li F, Neal J, Lemmon M, Walther Z, Politi K, Goldberg S. Efficacy of Osimertinib in Patients with Lung Cancer Positive for Uncommon EGFR Exon 19 Deletion Mutations. Clinical Cancer Research 2023, 29: of1-of8. PMID: 36913537, PMCID: PMC10493186, DOI: 10.1158/1078-0432.ccr-22-3497.Peer-Reviewed Original ResearchConceptsProgression-free survivalNon-small cell lung cancerInferior progression-free survivalMulticenter retrospective cohortEfficacy of osimertinibMulti-institutional cohortCell lung cancerExon 19 deletion mutationUncommon EGFRRetrospective cohortClinical outcomesClinical efficacyLung cancerOsimertinib efficacyEGFR mutationsPreclinical modelsEx19delPatientsAACR Genie databaseLater linesOsimertinibMutant cohortFirst lineCohortEfficacyManagement of patients with brain metastases from NSCLC without a genetic driver alteration: upfront radiotherapy or immunotherapy?
Merkin R, Chiang V, Goldberg S. Management of patients with brain metastases from NSCLC without a genetic driver alteration: upfront radiotherapy or immunotherapy? Therapeutic Advances In Medical Oncology 2023, 15: 17588359231175438. PMID: 37275964, PMCID: PMC10233588, DOI: 10.1177/17588359231175438.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsBrain metastasesTargetable genetic alterationsLocal therapyLung cancerStereotactic radiosurgeryDeath 1 ligand 1 expressionManagement of BMSole metastatic siteStage IV diseaseWhole brain radiotherapyLigand 1 expressionPD-L1 expressionProspective clinical trialsTime of diagnosisManagement of patientsCell lung cancerCancer-related deathGenetic alterationsCentral nervous systemGenetic driver alterationsAnaplastic lymphoma kinaseEpidermal growth factor receptorGrowth factor receptorUpfront radiotherapy
2022
Biochemical and structural basis for differential inhibitor sensitivity of EGFR with distinct exon 19 mutations
van Alderwerelt van Rosenburgh I, Lu D, Grant M, Stayrook S, Phadke M, Walther Z, Goldberg S, Politi K, Lemmon M, Ashtekar K, Tsutsui Y. Biochemical and structural basis for differential inhibitor sensitivity of EGFR with distinct exon 19 mutations. Nature Communications 2022, 13: 6791. PMID: 36357385, PMCID: PMC9649653, DOI: 10.1038/s41467-022-34398-z.Peer-Reviewed Original ResearchCancer of the Lung
Morgensztern D, Boffa D, Chen A, Dhanasopon A, Goldberg S, Decker R, Devarakonda S, Ko J, Soto L, Waqar S, Wistuba I, Herbst R. Cancer of the Lung. 2022, 1-29. DOI: 10.1002/9781119000822.hfcm085.pub2.Peer-Reviewed Original ResearchEP08.02-019 Phase 1/2 Study of BLU-701, a Highly Selective EGFR Inhibitor, in Patients With EGFR-Mutant Non-Small Cell Lung Cancer
Spira A, Spigel D, Camidge R, de Langen A, Kim T, Goto K, Elamin Y, Shum E, Reckamp K, Rotow J, Goldberg S, Gadgeel S, Leal T, Albayya F, Fitzpatrick S, Louie-Gao M, Parepally J, Zalutskaya A, Yu H. EP08.02-019 Phase 1/2 Study of BLU-701, a Highly Selective EGFR Inhibitor, in Patients With EGFR-Mutant Non-Small Cell Lung Cancer. Journal Of Thoracic Oncology 2022, 17: s406. DOI: 10.1016/j.jtho.2022.07.701.Peer-Reviewed Original ResearchOA03.06 CodeBreaK 100/101: First Report of Safety/Efficacy of Sotorasib in Combination with Pembrolizumab or Atezolizumab in Advanced KRAS p.G12C NSCLC
Li B, Falchook G, Durm G, Burns T, Skoulidis F, Ramalingam S, Spira A, Bestvina C, Goldberg S, Veluswamy R, Iams W, Chiappori A, Lemech C, Meloni A, Ebiana V, Dai T, Gauto D, Varrieur T, Snyder W, Govindan R. OA03.06 CodeBreaK 100/101: First Report of Safety/Efficacy of Sotorasib in Combination with Pembrolizumab or Atezolizumab in Advanced KRAS p.G12C NSCLC. Journal Of Thoracic Oncology 2022, 17: s10-s11. DOI: 10.1016/j.jtho.2022.07.025.Peer-Reviewed Original ResearchP1.10-01 Phase 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. P1.10-01 Phase 3 Study of Durvalumab Combined with Oleclumab or Monalizumab in Patients with Unresectable Stage III NSCLC (PACIFIC-9). Journal Of Thoracic Oncology 2022, 17: s107. DOI: 10.1016/j.jtho.2022.07.179.Peer-Reviewed Original Research