2023
Association Between Biomarkers and Clinical Outcomes of Pembrolizumab Monotherapy in Patients With Metastatic Triple-Negative Breast Cancer: KEYNOTE-086 Exploratory Analysis.
Loi S, Salgado R, Schmid P, Cortes J, Cescon D, Winer E, Toppmeyer D, Rugo H, De Laurentiis M, Nanda R, Iwata H, Awada A, Tan A, Sun Y, Karantza V, Wang A, Huang L, Saadatpour A, Cristescu R, Yearley J, Lunceford J, Jelinic P, Adams S. Association Between Biomarkers and Clinical Outcomes of Pembrolizumab Monotherapy in Patients With Metastatic Triple-Negative Breast Cancer: KEYNOTE-086 Exploratory Analysis. JCO Precision Oncology 2023, 7: e2200317. PMID: 37099733, DOI: 10.1200/po.22.00317.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerTriple-negative breast cancerClinical outcomesPembrolizumab monotherapyPD-L1Metastatic diseaseGEP signaturesBreast cancerStromal tumor-infiltrating lymphocytesT-cell-inflamed gene expression profileExploratory biomarker analysisMore systemic therapiesPD-L1 CPSTumor PD-L1PD-L1 statusTumor-infiltrating lymphocytesImproved clinical outcomesTumor mutational burdenSignature 3Mutational signature 3Cohort BDifferentiation 8Systemic therapyCohort ACombined cohort
2021
PD-L1 Immunohistochemistry Assay Comparison in Atezolizumab Plus nab-Paclitaxel–Treated Advanced Triple-Negative Breast Cancer
Rugo HS, Loi S, Adams S, Schmid P, Schneeweiss A, Barrios CH, Iwata H, Diéras V, Winer EP, Kockx MM, Peeters D, Chui SY, Lin JC, Nguyen-Duc A, Viale G, Molinero L, Emens LA. PD-L1 Immunohistochemistry Assay Comparison in Atezolizumab Plus nab-Paclitaxel–Treated Advanced Triple-Negative Breast Cancer. Journal Of The National Cancer Institute 2021, 113: 1733-1743. PMID: 34097070, PMCID: PMC8634452, DOI: 10.1093/jnci/djab108.Peer-Reviewed Original ResearchConceptsNab-paclitaxelPD-L1Metastatic triple-negative breast cancer patientsAdvanced triple-negative breast cancerAnalytical concordanceTriple-negative breast cancer patientsTriple-negative breast cancerDouble-positive casesCombined positive scorePD-L1 statusPD-L1 assaysBreast cancer patientsSingle positive caseMore patientsSP263 assaysClinical outcomesClinical benefitCancer patientsClinical activityBreast cancerSP142SP263PatientsPhase IIIPositive scoreALEXANDRA/IMpassion030: A phase 3 study of standard adjuvant chemotherapy with or without atezolizumab in patients with early-stage triple-negative breast cancer.
Saji S, McArthur H, Ignatiadis M, Bailey A, El-Abed S, Brandao M, Metzger O, Lai C, Guillaume S, Fumagalli D, Agbor-tarh D, Seiller A, Xifro R, Honvault V, Viale G, DuFrane C, Barata T, Winer E, Gelber R, Piccart-Gebhart M. ALEXANDRA/IMpassion030: A phase 3 study of standard adjuvant chemotherapy with or without atezolizumab in patients with early-stage triple-negative breast cancer. Journal Of Clinical Oncology 2021, 39: tps597-tps597. DOI: 10.1200/jco.2021.39.15_suppl.tps597.Peer-Reviewed Original ResearchTriple-negative breast cancerInvasive disease-free survivalEarly-stage triple-negative breast cancerPD-L1Breast cancerAdjuvant chemotherapyStage triple-negative breast cancerMetastatic triple-negative breast cancerPD-L1 negative tumorsF. Hoffmann-La Roche LtdBreast International GroupOperable stage IIRandomized phase 3Same chemotherapy regimenStandard adjuvant chemotherapyCentral pathology reviewDisease-free survivalPD-L1 statusPhase 3 studyPhase 3 trialType of surgeryNegative breast cancerQuality of lifeAtezolizumab 1200Weekly paclitaxel
2020
Effect of Eribulin With or Without Pembrolizumab on Progression-Free Survival for Patients With Hormone Receptor–Positive, ERBB2-Negative Metastatic Breast Cancer
Tolaney SM, Barroso-Sousa R, Keenan T, Li T, Trippa L, Vaz-Luis I, Wulf G, Spring L, Sinclair NF, Andrews C, Pittenger J, Richardson ET, Dillon D, Lin NU, Overmoyer B, Partridge AH, Van Allen E, Mittendorf EA, Winer EP, Krop IE. Effect of Eribulin With or Without Pembrolizumab on Progression-Free Survival for Patients With Hormone Receptor–Positive, ERBB2-Negative Metastatic Breast Cancer. JAMA Oncology 2020, 6: 1598-1605. PMID: 32880602, PMCID: PMC7489368, DOI: 10.1001/jamaoncol.2020.3524.Peer-Reviewed Original ResearchConceptsProgression-free survivalObjective response rateTumor-infiltrating lymphocytesTumor mutational burdenPD-L1 statusOverall survivalHormonal therapyPrior linesPD-L1Clinical trialsMedian numberDay 1Cell death ligand 1 (PD-L1) inhibitorsERBB2-negative metastatic breast cancerMedian progression-free survivalDeath ligand 1 (PD-L1) inhibitorsEnd pointCause adverse eventsEfficacy of eribulinHormone receptor positiveMulticenter phase 2PD-L1 22C3Treatment-related deathsLines of chemotherapyPrimary end point
2019
289TiP ALEXANDRA/IMpassion030: A phase III study of standard adjuvant chemotherapy with or without atezolizumab in early stage triple negative breast cancer
Ignatiadis M, McArthur H, Bailey A, Martinez J, de Azambuja E, Metzger O, Lai C, Franzoi M, Goulioti T, Daly F, Bouhlel A, Balta V, Maetens M, Viale G, André B, DuFRane C, Nguyen D, Gelber R, Piccart M, Winer E. 289TiP ALEXANDRA/IMpassion030: A phase III study of standard adjuvant chemotherapy with or without atezolizumab in early stage triple negative breast cancer. Annals Of Oncology 2019, 30: v97. DOI: 10.1093/annonc/mdz240.112.Peer-Reviewed Original ResearchTriple-negative breast cancerInvasive disease-free survivalEarly-stage triple-negative breast cancerStage triple-negative breast cancerBreast International GroupNegative breast cancerBreast cancerAdjuvant chemotherapyPD-L1Seattle GeneticsRoche/GenentechMetastatic triple-negative breast cancerRoche-GenentechJules BordetOperable stage IIRandomized phase 3Same chemotherapy regimenStandard adjuvant chemotherapyCentral pathology reviewDisease-free survivalPD-L1 statusPhase 3 trialPhase III studyLymph node statusPD-L1 antibodiesLBA20 Performance of PD-L1 immunohistochemistry (IHC) assays in unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC): Post-hoc analysis of IMpassion130
Rugo H, Loi S, Adams S, Schmid P, Schneeweiss A, Barrios C, Iwata H, Dieras V, Winer E, Kockx M, Peeters D, Chui S, Lin J, Duc A, Viale G, Molinero L, Emens L. LBA20 Performance of PD-L1 immunohistochemistry (IHC) assays in unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC): Post-hoc analysis of IMpassion130. Annals Of Oncology 2019, 30: v858-v859. DOI: 10.1093/annonc/mdz394.009.Peer-Reviewed Original ResearchF. Hoffmann-La Roche LtdBiomarker-evaluable populationGenentech/RocheOverall percentage agreementMetastatic triple-negative breast cancerPD-L1 statusPD-L1F. Hoffmann-La RocheBristol-Myers SquibbDaiichi SankyoPercentage agreementOS benefitHoffmann-La RocheRoche/GenentechEli LillyPD-L1 IHC assaysPD-L1 immunohistochemistry assaysIHC assaysBoehringer IngelheimBreast Cancer Research FoundationSeattle GeneticsTriple-negative breast cancerNegative percentage agreementGreater clinical benefitPositive percentage agreementA phase II study of pembrolizumab in combination with palliative radiotherapy (RT) for hormone receptor-positive (HR+) metastatic breast cancer (MBC).
Barroso-Sousa R, Krop I, Trippa L, Tan-Wasielewski Z, Li T, Osmani W, Andrews C, Dillon D, Richardson E, Winer E, Mittendorf E, Schoenfeld J, Tolaney S. A phase II study of pembrolizumab in combination with palliative radiotherapy (RT) for hormone receptor-positive (HR+) metastatic breast cancer (MBC). Journal Of Clinical Oncology 2019, 37: 1047-1047. DOI: 10.1200/jco.2019.37.15_suppl.1047.Peer-Reviewed Original ResearchMetastatic breast cancerNeutrophil/lymphocyte ratioObjective response rateProgression-free survivalTumor-infiltrating lymphocytesPalliative radiotherapyAdverse eventsHormone receptor-positive metastatic breast cancerPhase II single-arm studyMedian progression-free survivalCause adverse eventsDistant tumor responsesECOG PS 1Prior cytotoxic therapyImmune checkpoint inhibitorsPD-L1 expressionPD-L1 statusPhase II studySingle-arm studyTotal RT doseUnexpected adverse eventsECOG PSEligible ptsRECIST v1.1Measurable lesionsRandomized phase II study of eribulin mesylate (E) with or without pembrolizumab (P) for hormone receptor-positive (HR+) metastatic breast cancer (MBC).
Tolaney S, Barroso-Sousa R, Keenan T, Trippa L, Hu J, Luis I, Wulf G, Spring L, Sinclair N, Andrews C, Pittenger J, Richardson E, Dillon D, Lin N, Overmoyer B, Partridge A, VanAllen E, Mittendorf E, Winer E, Krop I. Randomized phase II study of eribulin mesylate (E) with or without pembrolizumab (P) for hormone receptor-positive (HR+) metastatic breast cancer (MBC). Journal Of Clinical Oncology 2019, 37: 1004-1004. DOI: 10.1200/jco.2019.37.15_suppl.1004.Peer-Reviewed Original ResearchProgression-free survivalObjective response rateNeutrophil-lymphocyte ratioTumor-infiltrating lymphocytesTumor mutation burdenOverall survivalPrior linesMedian progression-free survivalCheckpoint inhibitor monotherapyMedian prior linesKey secondary endpointLines of chemotherapyPD-L1 statusTime of progressionChemotherapy 1Eligible patientsHormonal therapyPrimary endpointProtocol therapySecondary endpointsInhibitor monotherapyArm BMedian ageArm ATherapy 2