2025
Lenvatinib Plus Pembrolizumab, Pemetrexed, and a Platinum as First-Line Therapy for Metastatic Nonsquamous Non–Small-Cell Lung Cancer: Phase 3 LEAP-006 Study
Herbst R, Cho B, Zhou C, Burotto M, Dols M, Sendur M, Moiseyenko V, Casarini I, Nishio M, Hui R, Pons-Tostivint E, Dudnik J, Ahmed S, Okpara C, Dutcus C, Yin L, Luo Y, Chirovsky D, Bhagwati N, Abreu D. Lenvatinib Plus Pembrolizumab, Pemetrexed, and a Platinum as First-Line Therapy for Metastatic Nonsquamous Non–Small-Cell Lung Cancer: Phase 3 LEAP-006 Study. Journal Of Thoracic Oncology 2025 PMID: 40419140, DOI: 10.1016/j.jtho.2025.05.016.Peer-Reviewed Original ResearchNonsquamous non-small-cell lung cancerProgression-free survivalMetastatic nonsquamous non-small-cell lung cancerNonsquamous NSCLCNon-small-cell lung cancerFirst-line pembrolizumabOverall survivalTargetable genetic alterationsPlacebo armGenetic alterationsLung cancerTreatment-related adverse eventsFirst-line therapyMedian follow-upDouble-blind studyPrimary endpointPembrolizumabLenvatinibAdverse eventsChemotherapyFollow-upDisease progressionSafety signalsPemetrexedMonthsThe evolving immuno-angiogenic paradigm in NSCLC: lessons from ivonescimab
Herbst R, Chen L. The evolving immuno-angiogenic paradigm in NSCLC: lessons from ivonescimab. Nature Reviews Clinical Oncology 2025, 22: 461-462. PMID: 40329050, DOI: 10.1038/s41571-025-01024-y.Peer-Reviewed Original ResearchAdvanced-stage non-small-cell lung cancerNon-small-cell lung cancerProgression-free survivalOverall survival resultsAntitumour immunityReverse immunosuppressionTumor vasculatureVEGF antibodySurvival resultsLung cancerPembrolizumabNSCLCImmunosuppressionTumorPatientsCancerVasculatureDiverse populationsMolecular residual disease analysis of adjuvant osimertinib in resected EGFR-mutated stage IB–IIIA non-small-cell lung cancer
Herbst R, John T, Grohé C, Goldman J, Kato T, Laktionov K, Bonanno L, Tiseo M, Majem M, Dómine M, Ahn M, Kowalski D, Pérol M, Sriuranpong V, Özgüroğlu M, Bhetariya P, Markovets A, Rukazenkov Y, Muldoon C, Robichaux J, Hartmaier R, Tsuboi M, Wu Y. Molecular residual disease analysis of adjuvant osimertinib in resected EGFR-mutated stage IB–IIIA non-small-cell lung cancer. Nature Medicine 2025, 31: 1958-1968. PMID: 40097663, PMCID: PMC12176615, DOI: 10.1038/s41591-025-03577-y.Peer-Reviewed Original ResearchConceptsMolecular residual diseaseDisease-free survivalNon-small-cell lung cancerDisease-free survival eventsEvent-free rateAdjuvant osimertinibOsimertinib treatmentStage IB-IIIA non-small-cell lung cancerLung cancerOverall survival improvementEvent-free statusPosttreatment follow-upExploratory post hoc analysisYear adjuvant treatmentPost hoc analysisDFS eventsOsimertinib groupResidual diseaseTreatment discontinuationPlacebo groupAdjuvant therapyAdjuvant treatmentSurvival improvementOsimertinibFollow-up
2024
CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors
Skoulidis F, Araujo H, Do M, Qian Y, Sun X, Cobo A, Le J, Montesion M, Palmer R, Jahchan N, Juan J, Min C, Yu Y, Pan X, Arbour K, Vokes N, Schmidt S, Molkentine D, Owen D, Memmott R, Patil P, Marmarelis M, Awad M, Murray J, Hellyer J, Gainor J, Dimou A, Bestvina C, Shu C, Riess J, Blakely C, Pecot C, Mezquita L, Tabbó F, Scheffler M, Digumarthy S, Mooradian M, Sacher A, Lau S, Saltos A, Rotow J, Johnson R, Liu C, Stewart T, Goldberg S, Killam J, Walther Z, Schalper K, Davies K, Woodcock M, Anagnostou V, Marrone K, Forde P, Ricciuti B, Venkatraman D, Van Allen E, Cummings A, Goldman J, Shaish H, Kier M, Katz S, Aggarwal C, Ni Y, Azok J, Segal J, Ritterhouse L, Neal J, Lacroix L, Elamin Y, Negrao M, Le X, Lam V, Lewis W, Kemp H, Carter B, Roth J, Swisher S, Lee R, Zhou T, Poteete A, Kong Y, Takehara T, Paula A, Parra Cuentas E, Behrens C, Wistuba I, Zhang J, Blumenschein G, Gay C, Byers L, Gibbons D, Tsao A, Lee J, Bivona T, Camidge D, Gray J, Leighl N, Levy B, Brahmer J, Garassino M, Gandara D, Garon E, Rizvi N, Scagliotti G, Wolf J, Planchard D, Besse B, Herbst R, Wakelee H, Pennell N, Shaw A, Jänne P, Carbone D, Hellmann M, Rudin C, Albacker L, Mann H, Zhu Z, Lai Z, Stewart R, Peters S, Johnson M, Wong K, Huang A, Winslow M, Rosen M, Winters I, Papadimitrakopoulou V, Cascone T, Jewsbury P, Heymach J. CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors. Nature 2024, 635: 462-471. PMID: 39385035, PMCID: PMC11560846, DOI: 10.1038/s41586-024-07943-7.Peer-Reviewed Original ResearchNon-small-cell lung cancerImmune checkpoint blockadeTumor suppressor genePD-L1Advanced non-small-cell lung cancerCD8+ cytotoxic T cellsSuppressor geneCD4+ effector cellsDual immune checkpoint blockadeMouse modelPD-L1 inhibitor durvalumabSuppressive myeloid cellsPD-L1 inhibitorsImmune-related toxicitiesPD-(L)1 inhibitorsAnti-tumor efficacyCytotoxic T cellsMyeloid cell compartmentAdverse tumor microenvironmentAssociated with higher ratesAnti-tumor activityLoss of Keap1CTLA4 inhibitorsSTK11 alterationsCheckpoint blockade
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