2024
Quantitative Measurement of HER2 Expression in Non–Small Cell Lung Cancer With a High-Sensitivity Assay
Liu M, Vathiotis I, Robbins C, Chan N, Moutafi M, Burela S, Xirou V, Schalper K, Herbst R, Syrigos K, Rimm D. Quantitative Measurement of HER2 Expression in Non–Small Cell Lung Cancer With a High-Sensitivity Assay. Modern Pathology 2024, 37: 100556. PMID: 38964502, DOI: 10.1016/j.modpat.2024.100556.Peer-Reviewed Original ResearchNon-small cell lung cancerCases of non-small cell lung cancerNon-small cell lung cancer casesT-DXdCell lung cancerHER2 expressionBreast cancerRare case of non-small cell lung cancerQuantitative immunofluorescenceAntibody-drug conjugate trastuzumab deruxtecanLung cancerHER2 antibody-drug conjugatesNon-small cell lung cancer patientsDetecting HER2 expressionHER2-targeted therapyMetastatic breast cancerHER2 protein expressionBreast cancer casesHER2 protein levelsAntibody-drug conjugatesProportion of casesTrastuzumab deruxtecanNSCLC casesFrequency of casesImmunohistochemistry scoreUpdated results from COAST, a phase 2 study of durvalumab (D) ± oleclumab (O) or monalizumab (M) in patients (pts) with stage III unresectable non-small cell lung cancer (uNSCLC).
Aggarwal C, Martinez-Marti A, Majem M, Barlesi F, Carcereny E, Chu Q, Monnet I, Sanchez A, Dakhil S, Camidge D, Pillet M, Brown M, Dowson A, Cooper Z, Kumar R, Herbst R. Updated results from COAST, a phase 2 study of durvalumab (D) ± oleclumab (O) or monalizumab (M) in patients (pts) with stage III unresectable non-small cell lung cancer (uNSCLC). Journal Of Clinical Oncology 2024, 42: 8046-8046. DOI: 10.1200/jco.2024.42.16_suppl.8046.Peer-Reviewed Original ResearchUnresectable non-small cell lung cancerStage III unresectable non-small cell lung cancerProgression free survivalImmune-mediated AEConcurrent chemoradiotherapyPhase 2 studyNon-small cell lung cancerProlonged progression free survivalECOG PS 0Suppress antitumor immunityMedian follow-upCell lung cancerExpression of CD73Anti-CD73Anti-NKG2AImmunotherapy combinationsAntitumor immunityConsolidation therapyPD-L1Free survivalImmune checkpointsPS 0Open-labelProgressive diseaseDiscontinued treatmentSWOG S2302, PRAGMATICA-LUNG: A prospective randomized study of ramucirumab plus pembrolizumab (PR) versus standard of care (SOC) for participants previously treated with immunotherapy for stage IV or recurrent non-small cell lung cancer.
Reckamp K, Redman M, Dragnev K, Iams W, Henick B, Miao J, LeBlanc M, Carrizosa D, Herbst R, Blanke C, Gray J. SWOG S2302, PRAGMATICA-LUNG: A prospective randomized study of ramucirumab plus pembrolizumab (PR) versus standard of care (SOC) for participants previously treated with immunotherapy for stage IV or recurrent non-small cell lung cancer. Journal Of Clinical Oncology 2024, 42: tps8657-tps8657. DOI: 10.1200/jco.2024.42.16_suppl.tps8657.Peer-Reviewed Original ResearchNon-small cell lung cancerAdvanced non-small cell lung cancerStandard of careCell lung cancerPD-(L)1Overall survivalAdverse eventsRecurrent non-small cell lung cancerLung cancerTreatment-related adverse eventsRandomized phase II trialStandard of care treatmentPlatinum-based therapyTreated with immunotherapyPhase II trialLog-rank testCompare OSInhibitor therapyII trialCombination therapyStatistically significant improvementTumor resistanceSafety profileTherapeutic optionsRandomized studyLung-MAP S1800D: A phase II/III study of N-803 (ALT-803) plus pembrolizumab versus standard of care in participants with stage IV or recurrent non-small cell lung cancer (NSCLC) previously treated with anti-PD-1 or anti-PD-L1 therapy.
Wrangle J, Redman M, Husain H, Reckamp K, Stinchcombe T, Edelman M, Leal T, Faller B, Minichiello K, Borghaei H, Kelly K, Herbst R, Gray J. Lung-MAP S1800D: A phase II/III study of N-803 (ALT-803) plus pembrolizumab versus standard of care in participants with stage IV or recurrent non-small cell lung cancer (NSCLC) previously treated with anti-PD-1 or anti-PD-L1 therapy. Journal Of Clinical Oncology 2024, 42: 2619-2619. DOI: 10.1200/jco.2024.42.16_suppl.2619.Peer-Reviewed Original ResearchNon-small cell lung cancerAdvanced non-small cell lung cancerProgression-free survivalPhase II/III studiesN-803Overall survivalIL-15Resistance cohortRecurrent non-small cell lung cancerTreated advanced non-small cell lung cancerLung cancerTreated with anti-PD-1Anti-PD-L1 therapyIL-15 receptor alphaAnti-PD-1Anti-PD-L1Performance of immunotherapiesAnti-PD-(L)1Cell lung cancerCancer related deathGamma-chain familyClinical unmet needStandard of careALT-803Secondary endpointsMolecular residual disease (MRD) analysis from the ADAURA trial of adjuvant (adj) osimertinib in patients (pts) with resected EGFR-mutated (EGFRm) stage IB–IIIA non-small cell lung cancer (NSCLC).
John T, Grohe C, Goldman J, Kato T, Laktionov K, Bonanno L, Tiseo M, Majem M, Domine M, Ahn M, Perol M, Hartmaier R, Robichaux J, Bhetariya P, Markovets A, Rukazenkov Y, Muldoon C, Herbst R, Tsuboi M, Wu Y. Molecular residual disease (MRD) analysis from the ADAURA trial of adjuvant (adj) osimertinib in patients (pts) with resected EGFR-mutated (EGFRm) stage IB–IIIA non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2024, 42: 8005-8005. DOI: 10.1200/jco.2024.42.16_suppl.8005.Peer-Reviewed Original ResearchDisease-free survivalMolecular residual diseaseNon-small cell lung cancerDisease-free survival eventsDisease recurrenceEGFR-mutantOverall survivalStage IB-IIIA non-small cell lung cancerEGFR T790M resistance mutationT790M resistance mutationMedian follow-up timeEGFR-TKI sensitivityResected tumor tissueCell lung cancerTumor-specific variantsMedian lead timeWhole-exome sequencingDetection of ctDNAADAURA studyADAURA trialInvestigator-assessedMolecular recurrenceEGFR-TKIsResidual diseaseEligible ptsSummary of Research: Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC
Tsuboi M, Herbst R, John T, Kato T, Majem M, Grohé C, Wang J, Goldman J, Lu S, de Marinis F, Shepherd F, Lee K, Le N, Dechaphunkul A, Kowalski D, Bonanno L, Dómine M, Poole L, Bolanos A, Rukazenkov Y, Wu Y. Summary of Research: Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC. Targeted Oncology 2024, 19: 131-134. PMID: 38466534, PMCID: PMC10963460, DOI: 10.1007/s11523-024-01034-3.Peer-Reviewed Original ResearchNon-small cell lung cancerEGFR-mutant non-small cell lung cancerResected EGFR-mutant non-small cell lung cancerEpidermal growth factor receptorOverall survivalEGFR-mutantStage IB-IIIA non-small cell lung cancerPatients treated with osimertinibDisease-free survivalStage II-IIIAEffects of osimertinibCell lung cancerGrowth factor receptorCancer cell deathRisk of deathADAURA studyLength of time patientsOsimertinib groupTumor shrinkagePlacebo groupCancer-freeOsimertinibLung cancerFactor receptorCancer cells
2023
Understanding health-related quality of life measures used in early-stage non-small cell lung cancer clinical trials: A review
Majem M, Basch E, Cella D, Garon E, Herbst R, Leighl N. Understanding health-related quality of life measures used in early-stage non-small cell lung cancer clinical trials: A review. Lung Cancer 2023, 187: 107419. PMID: 38070301, DOI: 10.1016/j.lungcan.2023.107419.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerEarly-stage diseaseHealth-related qualityClinical trialsEarly-stage non-small cell lung cancerTreatment-related adverse effectsAppropriate HRQoL instrumentNSCLC clinical trialsCell lung cancerLong-term treatmentLung cancer clinical trialsCancer clinical researchCancer clinical trialsAdjuvant treatmentAdvanced diseaseHRQOL assessmentTreatment landscapeDisease recurrenceHRQoL instrumentsLung cancerDisease progressionLife measuresHRQoLNarrative reviewHealthcare professionals606 IMpower110: Tertiary lymphoid structures (TLS) and clinical outcomes in advanced non-small cell lung cancer (NSCLC) treated with first-line atezolizumab or chemotherapy
Srivastava M, Gayevskiy V, Ma V, Estay I, Rodas M, Rajendran B, Hoang T, Ballinger M, Amin R, Herbst R, Marinis F, Giaccone G, Jassem J, Spigel D, Schalper K, Koeppen H, Shames D, Johnston R, Giltnane J, Nabet B. 606 IMpower110: Tertiary lymphoid structures (TLS) and clinical outcomes in advanced non-small cell lung cancer (NSCLC) treated with first-line atezolizumab or chemotherapy. 2023, a690-a690. DOI: 10.1136/jitc-2023-sitc2023.0606.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 ResearchNon-small cell lung cancerCell lung cancerAdenosinergic pathwayLung cancerImmunotherapy targetClinical significanceCancerLBA63 SAPPHIRE: Phase III study of sitravatinib plus nivolumab versus docetaxel in patients with previously treated advanced non-squamous non-small cell lung cancer (NSCLC)
Borghaei H, Johnson M, Garon E, He K, Planchard D, Reck M, Popat S, Herbst R, Leal T, Dumoulin D, de Marinis F, Reynolds C, Theelen W, Percent I, Calderon V, Flandin A, Shazer R, Yan X, Harrigan R, Peters S. LBA63 SAPPHIRE: Phase III study of sitravatinib plus nivolumab versus docetaxel in patients with previously treated advanced non-squamous non-small cell lung cancer (NSCLC). Annals Of Oncology 2023, 34: s1308. DOI: 10.1016/j.annonc.2023.10.064.Peer-Reviewed Original ResearchBiomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results
Gutierrez M, Lam W, Hellmann M, Gubens M, Aggarwal C, Tan D, Felip E, Chiu J, Lee J, Yang J, Garon E, Finocchiaro G, Ahn M, Luft A, Landers G, Basso A, Ma H, Kobie J, Palcza J, Cristescu R, Fong L, Snyder A, Yuan J, Herbst R. Biomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results. Nature Medicine 2023, 29: 1718-1727. PMID: 37429923, DOI: 10.1038/s41591-023-02385-6.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerObjective response rateAdvanced non-small cell lung cancerCell lung cancerSafety profileCombination therapyLung cancerInvestigator-assessed objective response rateRandomized phase 2 studySolid Tumors version 1.1T-cell-inflamed gene expression profileGroup IIIBiomarker-defined subgroupsFirst-line pembrolizumabPhase 2 studyProgression-free survivalResponse Evaluation CriteriaSubset of patientsHeterogenous tumor microenvironmentData cutoffOverall survivalSecondary outcomesPrimary outcomeTreatment armsTMB assessmentOverall survival analysis from the ADAURA trial of adjuvant osimertinib in patients with resected EGFR-mutated (EGFRm) stage IB–IIIA non-small cell lung cancer (NSCLC).
Herbst R, Tsuboi M, John T, Kato T, Majem M, Grohé C, Wang J, Goldman J, Lu S, Su W, de Marinis F, Shepherd F, Lee K, Le N, Dechaphunkul A, Kowalski D, Poole L, Stachowiak M, Rukazenkov Y, Wu Y. Overall survival analysis from the ADAURA trial of adjuvant osimertinib in patients with resected EGFR-mutated (EGFRm) stage IB–IIIA non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2023, 41: lba3-lba3. DOI: 10.1200/jco.2023.41.17_suppl.lba3.Peer-Reviewed Original ResearchNon-small cell lung cancerStage IB-IIIA non-small cell lung cancerAdjuvant osimertinibOverall survival analysisOS HRAdjuvant chemotherapyOS benefitOS ratesII-IIIASurvival analysisDisease-free survival benefitFinal overall survival analysisGlobal phase III studyEGFR T790M resistance mutationII-IIIA diseaseStage IB-IIIAT790M resistance mutationTolerable safety profilePhase III studyCell lung cancerComplete tumor resectionEGFR-TKI sensitizingM resistance mutationExtended treatment durationADAURA studyECOG-ACRIN LUNG-MAP S1900E substudy: A phase II study of sotorasib in participants (Pts) with previously treated stage IV or recurrent KRAS G12C mutant non-squamous (Non-sq) non-small cell lung cancer (NSCLC).
Padda S, Redman M, Gerber D, Stinchcombe T, Waqar S, Leal T, Minichiello K, Reckamp K, Herbst R, Borghaei H, Brahmer J, Gray J, Kelly K, Ramalingam S, Neal J. ECOG-ACRIN LUNG-MAP S1900E substudy: A phase II study of sotorasib in participants (Pts) with previously treated stage IV or recurrent KRAS G12C mutant non-squamous (Non-sq) non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2023, 41: tps9143-tps9143. DOI: 10.1200/jco.2023.41.16_suppl.tps9143.Peer-Reviewed Original ResearchNon-squamous non-small cell lung cancerTarget sample sizeKRAS G12C inhibitorsCohort 1Eligible ptsBrain metastasesG12C inhibitorsPhase 2 open-label studyNon-small cell lung cancerAsymptomatic brain metastasesOpen-label studyPhase II studyUntreated brain metastasesCell lung cancerDuration of responsePresence of TP53Wild-type TP53Oral dailySecondary endpointsII studySystemic treatmentAccrual targetLung cancerCohort 2Clinical activityGenomic and transcriptomic analysis of checkpoint blockade response in advanced non-small cell lung cancer
Ravi A, Hellmann M, Arniella M, Holton M, Freeman S, Naranbhai V, Stewart C, Leshchiner I, Kim J, Akiyama Y, Griffin A, Vokes N, Sakhi M, Kamesan V, Rizvi H, Ricciuti B, Forde P, Anagnostou V, Riess J, Gibbons D, Pennell N, Velcheti V, Digumarthy S, Mino-Kenudson M, Califano A, Heymach J, Herbst R, Brahmer J, Schalper K, Velculescu V, Henick B, Rizvi N, Jänne P, Awad M, Chow A, Greenbaum B, Luksza M, Shaw A, Wolchok J, Hacohen N, Getz G, Gainor J. Genomic and transcriptomic analysis of checkpoint blockade response in advanced non-small cell lung cancer. Nature Genetics 2023, 55: 807-819. PMID: 37024582, PMCID: PMC10181943, DOI: 10.1038/s41588-023-01355-5.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerAdvanced non-small cell lung cancerCell lung cancerLung cancerAnti-PD-1/PD-L1 agentsCheckpoint blockade responsePD-L1 agentsTumor intrinsic subtypesCheckpoint inhibitorsCheckpoint blockadeTreatment landscapeImmunotherapy outcomesBlockade responseCohortBiological determinantsGenomic subgroupsEnhanced responseMolecular featuresWhole exomeCancerProminent associationOutcomesAssociationResponseNumber of associations
2022
635 KEYNOTE-495/KeyImPaCT: updated analysis of a biomarker-directed, randomized, phase 2 trial of pembrolizumab-based combination therapy for non-small cell lung cancer
Herbst R, Lam W, Hellmann M, Gubens M, Aggarwal C, Weng Tan D, Felip E, Chiu J, Lee J, Yang J, Garon E, Finocchiaro G, Ahn M, Luft A, Landers G, Basso A, Ma H, Kobie J, Palcza J, Cristescu R, Fong L, Snyder A, Yuan J, Gutierrez M. 635 KEYNOTE-495/KeyImPaCT: updated analysis of a biomarker-directed, randomized, phase 2 trial of pembrolizumab-based combination therapy for non-small cell lung cancer. 2022, a666-a666. DOI: 10.1136/jitc-2022-sitc2022.0635.Peer-Reviewed Original ResearchNon-small cell lung cancerPhase 2 trialCell lung cancerCombination therapyLung cancerTherapyCancerTrialsLBA5 Long-term tolerability of adjuvant osimertinib in patients with resected EGFR-mutated (EGFRm) stage IB–IIIA non-small cell lung cancer (NSCLC) from ADAURA
John T, Grohe C, Goldman J, De Marinis F, Kato T, Wang Q, Choi J, Melotti B, Fidler M, Sainsbury L, Stachowiak M, Taggart S, Wu Y, Tsuboi M, Herbst R, Tarruella M. LBA5 Long-term tolerability of adjuvant osimertinib in patients with resected EGFR-mutated (EGFRm) stage IB–IIIA non-small cell lung cancer (NSCLC) from ADAURA. Annals Of Oncology 2022, 33: s1548. DOI: 10.1016/j.annonc.2022.10.323.Peer-Reviewed Original Research296P Osimertinib as adjuvant therapy in patients (pts) with resected EGFR-mutated (EGFRm) stage IB-IIIA non-small cell lung cancer (NSCLC): Updated results from ADAURA
Wu Y, Tsuboi M, Grohe C, John T, Tarruella M, Wang J, Kato T, Goldman J, Kim S, Yu C, Vu H, Mukhametshina G, Akewanlop C, de Marinis F, Shepherd F, Urban D, Stachowiak M, Bolanos A, Huang X, Herbst R. 296P Osimertinib as adjuvant therapy in patients (pts) with resected EGFR-mutated (EGFRm) stage IB-IIIA non-small cell lung cancer (NSCLC): Updated results from ADAURA. Annals Of Oncology 2022, 33: s1548-s1549. DOI: 10.1016/j.annonc.2022.10.324.Peer-Reviewed Original ResearchQuantitative assessment of Siglec-15 expression in lung, breast, head, and neck squamous cell carcinoma and bladder cancer.
Shafi S, Aung T, Xirou V, Gavrielatou N, Vathiotis I, Fernandez A, Moutafi M, Yaghoobi V, Herbst R, Liu L, Langermann S, Rimm D. Quantitative assessment of Siglec-15 expression in lung, breast, head, and neck squamous cell carcinoma and bladder cancer. Laboratory Investigation 2022, 102: 1143-1149. PMID: 36775354, DOI: 10.1038/s41374-022-00796-6.Peer-Reviewed Original ResearchConceptsSiglec-15 expressionNon-small cell lung cancerNeck squamous cell carcinomaProgression-free survivalSquamous cell carcinomaCancer typesOverall survivalCell carcinomaBladder cancerImmune cellsSiglec-15PD-1/PD-L1 blockadePotential future clinical trialsQuantitative immunofluorescencePD-L1 blockadeStromal immune cellsImmune checkpoint blockadeCell lung cancerFuture clinical trialsNew potential targetsCheckpoint blockadePD-L1Lung cancerClinical trialsIntra-tumoral heterogeneityLBA47 Osimertinib as adjuvant therapy in patients (pts) with resected EGFR-mutated (EGFRm) stage IB-IIIA non-small cell lung cancer (NSCLC): Updated results from ADAURA
Tsuboi M, Wu Y, Grohe C, John T, Tarruella M, Wang J, Kato T, Goldman J, Kim S, Yu C, Vu H, Mukhametshina G, Akewanlop C, de Marinis F, Shepherd F, Urban D, Stachowiak M, Bolanos A, Huang X, Herbst R. LBA47 Osimertinib as adjuvant therapy in patients (pts) with resected EGFR-mutated (EGFRm) stage IB-IIIA non-small cell lung cancer (NSCLC): Updated results from ADAURA. Annals Of Oncology 2022, 33: s1413-s1414. DOI: 10.1016/j.annonc.2022.08.047.Peer-Reviewed Original ResearchQuantitative tissue analysis and role of myeloid cells in non-small cell lung cancer
Henick BS, Villarroel-Espindola F, Datar I, Sanmamed MF, Yu J, Desai S, Li A, Aguirre-Ducler A, Syrigos K, Rimm DL, Chen L, Herbst RS, Schalper KA. Quantitative tissue analysis and role of myeloid cells in non-small cell lung cancer. Journal For ImmunoTherapy Of Cancer 2022, 10: e005025. PMID: 35793873, PMCID: PMC9260844, DOI: 10.1136/jitc-2022-005025.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerSquamous cell carcinomaHuman non-small cell lung cancerMyeloid cell subsetsCell lung cancerHLA-DRLung adenocarcinomaMyeloid cellsCell subsetsLung cancerLung tissueQuantitative immunofluorescenceNon-tumor lung tissuesIndependent NSCLC cohortsLevels of CD68Multiplexed quantitative immunofluorescenceProinflammatory myeloid cellsHLA-DR expressionM1-like macrophagesImmature myeloid cell populationMyeloid cell populationsKRAS mutant tumorsNormal lung tissuesTumor epithelial cellsNon-tumor lung