2024
Phase Ib dose-escalation trial of taselisib (GDC-0032) in combination with HER2-directed therapies in patients with advanced HER2+ breast cancer
Grinshpun A, Ren S, Graham N, DeMeo M, Wrabel E, Carter J, Tayob N, Pereslete A, Hamilton E, Juric D, Mayer E, Tolaney S, Krop I, Metzger O. Phase Ib dose-escalation trial of taselisib (GDC-0032) in combination with HER2-directed therapies in patients with advanced HER2+ breast cancer. ESMO Open 2024, 9: 103465. PMID: 38833970, PMCID: PMC11179085, DOI: 10.1016/j.esmoop.2024.103465.Peer-Reviewed Original ResearchProgression-free survivalMaximal tolerated doseHER2+ breast cancerAdverse eventsBreast cancerT-DM1Cohort AHuman epidermal growth factor receptor 2-positiveEpidermal growth factor receptor 2-positiveHER2+) breast cancerMedian progression-free survivalAll-grade adverse eventsAssociated with significant toxicityCirculating tumor DNA analysisDevelopment of acquired resistanceHER2-directed regimensHER2-directed therapyAnti-HER2 therapyHER2-targeted therapyPhase Ib studyTumor DNA analysisPI3KDose escalationImprove disease controlOral inhibitorAnalysis of drug-related interstitial lung disease (ILD) inpatients (pts) treated with datopotamab deruxtecan (Dato-DXd).
Lisberg A, Bardia A, Shimizu T, Ahn M, Paz-Ares L, Meric-Bernstam F, Kitazono S, Krop I, Girard N, Tostivint E, Heist R, Cornelissen R, Pistilli B, Lee K, Howarth P, Gu W, Fairhurst R, Khan S, Okamoto I. Analysis of drug-related interstitial lung disease (ILD) inpatients (pts) treated with datopotamab deruxtecan (Dato-DXd). Journal Of Clinical Oncology 2024, 42: 8623-8623. DOI: 10.1200/jco.2024.42.16_suppl.8623.Peer-Reviewed Original ResearchNon-small cell lung cancerInterstitial lung diseaseDrug-related interstitial lung diseaseInterstitial lung disease incidenceBreast cancerTumor typesCases of interstitial lung diseaseCell lung cancerSolid tumor typesDuration of treatmentMultiple tumor typesAntibody drug conjugatesCheckpoint inhibitorsDrug interruptionDose reductionDrug withdrawalSolid tumorsAdverse eventsTumor indicationsLung cancerPooled analysisClinical dataLung diseasePT subgroupAdjudication committeePooled analysis by best confirmed response to trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2+ metastatic breast cancer (mBC) from DESTINY-Breast-01, -02, and -03.
Saura C, Cortés J, Modi S, Kim S, Hamilton E, Hurvitz S, Krop I, Curigliano G, Iwata H, Im S, Herbolsheimer P, Karnoub M, Gambhire D, Egorov A, Andre F. Pooled analysis by best confirmed response to trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2+ metastatic breast cancer (mBC) from DESTINY-Breast-01, -02, and -03. Journal Of Clinical Oncology 2024, 42: 1023-1023. DOI: 10.1200/jco.2024.42.16_suppl.1023.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsHER2+ metastatic breast cancerProgression-free survivalMetastatic breast cancerComplete responsePartial responseT-DXdOverall survivalPooled analysisInterstitial lung disease (ILD)/pneumonitisStable disease (SD)/progressive diseaseProlonged progression-free survivalDuration of responseIndependent central reviewNumerically lower ratesLonger treatment durationMetastatic settingRECIST v1.1Trastuzumab deruxtecanOS outcomesCentral reviewAdverse eventsBreast cancerTreatment durationDrug-relatedClinical management, monitoring, and prophylaxis of adverse events of special interest associated with datopotamab deruxtecan
Heist R, Sands J, Bardia A, Shimizu T, Lisberg A, Krop I, Yamamoto N, Kogawa T, Al-Hashimi S, Fung S, Galor A, Pisetzky F, Basak P, Lau C, Meric-Bernstam F. Clinical management, monitoring, and prophylaxis of adverse events of special interest associated with datopotamab deruxtecan. Cancer Treatment Reviews 2024, 125: 102720. PMID: 38502995, DOI: 10.1016/j.ctrv.2024.102720.Peer-Reviewed Original ResearchNon-small cell lung cancerTriple-negative breast cancerTrophoblast cell surface antigen 2Antibody drug conjugatesAdverse eventsHR+/HER2- BCDelivery of cytotoxic agents to tumor cellsBreast cancerCytotoxic agents to tumor cellsTopoisomerase I inhibitor payloadAgents to tumor cellsInterstitial lung disease/pneumonitisInfusion-related reactionsSolid tumor indicationsPhase I studyCell lung cancerNovel antibody drug conjugatesSystemic therapySafety profileSolid tumorsTumor indicationsTumor cellsLung cancerClinical managementClinical trials
2023
Trastuzumab deruxtecan in previously treated patients with HER2-positive metastatic breast cancer: updated survival results from a phase II trial (DESTINY-Breast01) ☆
Saura C, Modi S, Krop I, Park Y, Kim S, Tamura K, Iwata H, Tsurutani J, Sohn J, Mathias E, Liu Y, Cathcart J, Singh J, Yamashita T. Trastuzumab deruxtecan in previously treated patients with HER2-positive metastatic breast cancer: updated survival results from a phase II trial (DESTINY-Breast01) ☆. Annals Of Oncology 2023, 35: 302-307. PMID: 38092229, PMCID: PMC11322859, DOI: 10.1016/j.annonc.2023.12.001.Peer-Reviewed Original ResearchHER2-positive metastatic breast cancerTreatment-emergent adverse eventsMetastatic breast cancerObjective response rateProgression-free survivalDuration of responseIndependent central reviewT-DXdAdverse eventsOverall survivalTrastuzumab deruxtecanCentral reviewBreast cancerDrug-related treatment-emergent adverse eventsInterstitial lung disease/pneumonitisResponse rateMedian progression-free survivalPositive metastatic breast cancerHuman epidermal growth factor receptor 2End pointEpidermal growth factor receptor 2Sustained antitumor activityAntitumor activityMedian overall survivalPrimary end pointAn age-specific pooled analysis of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-positive (HER2+) metastatic breast cancer (mBC) from DESTINY-Breast01, -02, and -03.
Krop I, Wildiers H, Hurvitz S, Cortes J, Im S, Iwata H, Andre F, Saura C, Modi S, Kim S, Egorov A, Mathias E, Cathcart J, Cagnazzo A, Cheng Y, Park Y. An age-specific pooled analysis of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-positive (HER2+) metastatic breast cancer (mBC) from DESTINY-Breast01, -02, and -03. Journal Of Clinical Oncology 2023, 41: 1006-1006. DOI: 10.1200/jco.2023.41.16_suppl.1006.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsMetastatic breast cancerT-DXdGrade treatment-emergent adverse eventsHER2-positive metastatic breast cancerInterstitial lung disease/pneumonitisFavorable benefit-risk profileAge-specific efficacyGrade 5 eventsPooled safety analysisBenefit-risk profileYears of ageKey efficacy dataOlder ptsSerious AEsAdverse eventsTrastuzumab deruxtecanAdditional efficacyPooled analysisT-DM1Trastuzumab emtansineEfficacy dataBreast cancerSafety dataSafety outcomesTrastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial
André F, Hee Park Y, Kim S, Takano T, Im S, Borges G, Lima J, Aksoy S, Gavila Gregori J, De Laurentiis M, Bianchini G, Roylance R, Miyoshi Y, Armstrong A, Sinha R, Ruiz Borrego M, Lim E, Ettl J, Yerushalmi R, Zagouri F, Duhoux F, Fehm T, Gambhire D, Cathcart J, Wu C, Chu C, Egorov A, Krop I. Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial. The Lancet 2023, 401: 1773-1785. PMID: 37086745, DOI: 10.1016/s0140-6736(23)00725-0.Peer-Reviewed Original ResearchConceptsHER2-positive metastatic breast cancerMetastatic breast cancerPhysician's choice groupTreatment-emergent adverse eventsBlinded independent central reviewPhase 3 trialProgression-free survivalTrastuzumab deruxtecanIndependent central reviewBreast cancerPhysician's choiceAdverse eventsCentral reviewTrastuzumab emtansineEastern Cooperative Oncology Group performance statusCommon treatment-emergent adverse eventsHigher treatment-emergent adverse eventsMedian progression-free survivalPositive metastatic breast cancerFavorable benefit-risk profilePalmar-plantar erythrodysaesthesiaInterstitial lung diseaseBenefit-risk profileAntibody-drug conjugatesChoice group
2022
Phase Ib study of pembrolizumab in combination with trastuzumab emtansine for metastatic HER2-positive breast cancer
Waks AG, Keenan TE, Li T, Tayob N, Wulf GM, Richardson ET, Attaya V, Anderson L, Mittendorf EA, Overmoyer B, Winer EP, Krop IE, Agudo J, Van Allen EM, Tolaney SM. Phase Ib study of pembrolizumab in combination with trastuzumab emtansine for metastatic HER2-positive breast cancer. Journal For ImmunoTherapy Of Cancer 2022, 10: e005119. PMID: 36252998, PMCID: PMC9577940, DOI: 10.1136/jitc-2022-005119.Peer-Reviewed Original ResearchConceptsObjective response rateProgression-free survivalMetastatic breast cancerAdverse eventsBreast cancerT-DM1Immune biomarkersTrastuzumab emtansineHER2-positive metastatic breast cancerMetastatic HER2-positive breast cancerGrade 3 adverse eventsMedian progression-free survivalTreatment-related adverse eventsHuman epidermal growth factor receptor 2Cell death ligand 1HER2-positive breast cancerEpidermal growth factor receptor 2Dose-finding cohortPhase 2 dosePhase Ib studyPhase Ib trialAnti-HER2 therapyDose-limiting toxicityGrowth factor receptor 2Immune checkpoint blockadeLong-term safety of inavolisib (GDC-0077) in an ongoing phase 1/1b study evaluating monotherapy and in combination (combo) with palbociclib and/or endocrine therapy in patients (pts) with PIK3CA-mutated, hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer (BC).
Bedard P, Accordino M, Cervantes A, Gambardella V, Hamilton E, Italiano A, Juric D, Kalinsky K, Krop I, Oliveira M, Saura C, Schmid P, Turner N, Varga A, Shankar N, Schutzman J, Royer-Joo S, Martin M, Jhaveri K. Long-term safety of inavolisib (GDC-0077) in an ongoing phase 1/1b study evaluating monotherapy and in combination (combo) with palbociclib and/or endocrine therapy in patients (pts) with PIK3CA-mutated, hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer (BC). Journal Of Clinical Oncology 2022, 40: 1052-1052. DOI: 10.1200/jco.2022.40.16_suppl.1052.Peer-Reviewed Original ResearchBreast cancerPO QDHormone receptor-positive/HER2-negative metastatic breast cancerFrequent treatment-related adverse eventsFrequent treatment-related grade 3HER2-negative metastatic breast cancerTreatment-related adverse eventsTreatment-related grade 3G3-4 neutropeniaPhase 1/1b studyPhase 3 doseLong-term tolerabilityNew safety signalsOverall study populationPhase 3 studyMetastatic breast cancerPreliminary antitumor activityLong-term safetyFemale ptsEndocrine therapyPrior therapyDose intensityAdverse eventsArm BMedian ageCardiac outcomes of subjects on adjuvant trastuzumab emtansine vs paclitaxel in combination with trastuzumab for stage I HER2-positive breast cancer (ATEMPT) study (TBCRC033): a randomized controlled trial
Barroso-Sousa R, Tarantino P, Tayob N, Dang C, Yardley DA, Isakoff SJ, Valero V, Faggen M, Mulvey T, Bose R, Hu J, Weckstein D, Wolff AC, Reeder-Hayes K, Rugo HS, Ramaswamy B, Zuckerman D, Hart L, Gadi VK, Constantine M, Cheng K, Briccetti F, Schneider B, Garrett AM, Marcom K, Albain K, DeFusco P, Tung N, Ardman B, Nanda R, Jankowitz RC, Rimawi M, Abramson V, Pohlmann PR, Van Poznak C, Forero-Torres A, Liu M, Ruddy KJ, Zheng Y, Rosenberg SM, Gelber RD, Trippa L, Barry W, DeMeo M, Burstein H, Partridge A, Winer EP, Krop I, Tolaney SM. Cardiac outcomes of subjects on adjuvant trastuzumab emtansine vs paclitaxel in combination with trastuzumab for stage I HER2-positive breast cancer (ATEMPT) study (TBCRC033): a randomized controlled trial. Npj Breast Cancer 2022, 8: 18. PMID: 35173164, PMCID: PMC8850608, DOI: 10.1038/s41523-022-00385-2.Peer-Reviewed Original ResearchLeft ventricular ejection fractionHER2-positive breast cancerAdjuvant T-DM1Adjuvant trastuzumab emtansineT-DM1Adverse eventsCardiac outcomesTrastuzumab emtansineBreast cancerStage I HER2-positive breast cancerAsymptomatic left ventricular ejection fractionBaseline left ventricular ejection fractionAnthracycline-free regimensAsymptomatic LVEF declineResidual invasive diseaseT-DM1 armCardiac adverse eventsVentricular systolic dysfunctionSignificant adverse eventsVentricular ejection fractionBody mass indexFavorable toxicity profilePotential therapeutic optionBreast Cancer StudyAdjuvant paclitaxel
2021
Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis
Curigliano G, Mueller V, Borges V, Hamilton E, Hurvitz S, Loi S, Murthy R, Okines A, Paplomata E, Cameron D, Carey L, Gelmon K, Hortobagyi G, Krop I, Loibl S, Pegram M, Slamon D, Ramos J, Feng W, Winer E. Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis. Annals Of Oncology 2021, 33: 321-329. PMID: 34954044, DOI: 10.1016/j.annonc.2021.12.005.Peer-Reviewed Original ResearchConceptsProgression-free survivalMetastatic breast cancerPlacebo-combination groupOverall survivalCombination groupBreast cancerHER2CLIMB trialBrain metastasesMedian durationSafety outcomesPrimary analysisFinal overall survival analysisHuman epidermal growth factor receptor 2 positive metastatic breast cancerPositive metastatic breast cancerMeaningful survival benefitMedian overall survivalPlacebo-controlled trialOverall study populationOverall survival analysisFinal OSMetastatic HER2Placebo combinationAdverse eventsLast patientPrespecified subgroupsTrastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2–Positive Early Breast Cancer: The Phase III KAITLIN Study
Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2–Positive Early Breast Cancer: The Phase III KAITLIN Study. Journal Of Clinical Oncology 2021, 40: 438-448. PMID: 34890214, PMCID: PMC8824393, DOI: 10.1200/jco.21.00896.Peer-Reviewed Original ResearchConceptsInvasive disease-free survivalOverall populationTrastuzumab emtansineHigh-risk human epidermal growth factor receptorHuman epidermal growth factor receptor 2End pointEpidermal growth factor receptor 2Early breast cancer treatmentHuman epidermal growth factor receptorAnthracycline-based chemotherapyCoprimary end pointsPrimary end pointDisease-free survivalSerious adverse eventsEarly breast cancerGlobal health statusGrowth factor receptor 2Treatment completion ratesStandard of careBreast cancer treatmentFactor receptor 2Epidermal growth factor receptorGrowth factor receptorEndocrine therapyAdverse eventsUpdated results of tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB).
Curigliano G, Mueller V, Borges V, Hamilton E, Hurvitz S, Loi S, Murthy R, Okines A, Paplomata E, Cameron D, Carey L, Gelmon K, Hortobagyi G, Krop I, Loibl S, Pegram M, Slamon D, Ramos J, Zhang C, Winer E. Updated results of tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB). Journal Of Clinical Oncology 2021, 39: 1043-1043. DOI: 10.1200/jco.2021.39.15_suppl.1043.Peer-Reviewed Original ResearchMetastatic breast cancerBrain metastasesOverall survivalTyrosine kinase inhibitorsBreast cancerPlacebo armAnalysis of OSOral tyrosine kinase inhibitorECOG performance statusPlacebo-controlled trialTotal study populationKaplan-Meier timeHER2CLIMB trialMeaningful prolongationMetastatic HER2Study medicationTolerability assessmentsMetastatic settingAdverse eventsDose modificationHazard ratioLast patientPerformance statusDisease progressionStudy population
2020
A Randomized Placebo Controlled Phase II Trial Evaluating Exemestane with or without Enzalutamide in Patients with Hormone Receptor–Positive Breast Cancer
Krop I, Abramson V, Colleoni M, Traina T, Holmes F, Garcia-Estevez L, Hart L, Awada A, Zamagni C, Morris PG, Schwartzberg L, Chan S, Gucalp A, Biganzoli L, Steinberg J, Sica L, Trudeau M, Markova D, Tarazi J, Zhu Z, O'Brien T, Kelly C, Winer E, Yardley D. A Randomized Placebo Controlled Phase II Trial Evaluating Exemestane with or without Enzalutamide in Patients with Hormone Receptor–Positive Breast Cancer. Clinical Cancer Research 2020, 26: 6149-6157. PMID: 32988969, DOI: 10.1158/1078-0432.ccr-20-1693.Peer-Reviewed Original ResearchConceptsProgression-free survivalHormone receptor-positive breast cancerReceptor-positive breast cancerPhase II trialEndocrine therapyBreast cancerII trialAR mRNACohort 1Higher AR mRNA levelsLower ESR1 mRNA levelsET-naïve patientsGrade adverse eventsPrior endocrine therapyMetastatic breast cancerAndrogen receptor inhibitorMRNA levelsAR mRNA levelsESR1 mRNA levelsEnzalutamide armITT populationTreat populationAdvanced diseasePrimary endpointAdverse eventsSingle-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis
Brastianos PK, Lee EQ, Cohen JV, Tolaney SM, Lin NU, Wang N, Chukwueke U, White MD, Nayyar N, Kim A, Alvarez-Breckenridge C, Krop I, Mahar MK, Bertalan MS, Shaw B, Mora JL, Goss N, Subramanian M, Nayak L, Dietrich J, Forst DA, Nahed BV, Batchelor TT, Shih HA, Gerstner ER, Moy B, Lawrence D, Giobbie-Hurder A, Carter SL, Oh K, Cahill DP, Sullivan RJ. Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis. Nature Medicine 2020, 26: 1280-1284. PMID: 32483359, DOI: 10.1038/s41591-020-0918-0.Peer-Reviewed Original ResearchConceptsPrimary endpointOpen-label phase 2 trialDose of pembrolizumabExtracranial disease progressionHigher adverse eventsPercentage of patientsPhase 2 studyPhase 2 trialSolid tumor malignanciesFraction of patientsDefinitive progressionUnacceptable toxicityAdverse eventsOverall survivalPatients 17Leptomeningeal carcinomatosisLeptomeningeal disseminationLung cancerDisease progressionOvarian cancerMetastatic cancerPembrolizumabBreast cancerGrade 3PatientsManagement of adverse events in patients with HER2+ metastatic breast cancer treated with tucatinib, trastuzumab, and capecitabine (HER2CLIMB).
Okines A, Paplomata E, Wahl T, Wright G, Sutherland S, Jakobsen E, Valdes F, Chan A, Clark A, Conlin A, Lustberg M, Specht J, Pluard T, Zhu X, Krop I, Gelmon K, Slamon D, Ramos J, An G, Hamilton E. Management of adverse events in patients with HER2+ metastatic breast cancer treated with tucatinib, trastuzumab, and capecitabine (HER2CLIMB). Journal Of Clinical Oncology 2020, 38: 1043-1043. DOI: 10.1200/jco.2020.38.15_suppl.1043.Peer-Reviewed Original ResearchAdverse eventsMedian timeControl armBreast cancerExposure-adjusted incidence ratesElevated liver enzymesMetastatic breast cancerCases of diarrheaMedian durationDose modificationTx groupIncidence rateLiver enzymesHigh incidenceDiarrheaTucatinibFirst onsetCapecitabineTrastuzumabHER2Significant inhibitionBilirubinLonger durationCycle 1PatientsA phase Ib study of pembrolizumab (pembro) plus trastuzumab emtansine (T-DM1) for metastatic HER2+ breast cancer (MBC).
Waks A, Keenan T, Li T, Tayob N, Wulf G, Richardson E, Mittendorf E, Overmoyer B, Krop I, Winer E, Van Allen E, Agudo J, Tolaney S. A phase Ib study of pembrolizumab (pembro) plus trastuzumab emtansine (T-DM1) for metastatic HER2+ breast cancer (MBC). Journal Of Clinical Oncology 2020, 38: 1046-1046. DOI: 10.1200/jco.2020.38.15_suppl.1046.Peer-Reviewed Original ResearchObjective response rateProgression-free survivalAdverse eventsT-DM1PD-L1 combined positive scoreTumor-infiltrating lymphocyte (TIL) statusClinical benefit rateDose-finding cohortMedian age 54Phase 2 dosePhase Ib studyCombined positive scoreAnti-PD1 antibodyPhase 1 trialDe-escalation designEligible patientsLymphocyte statusMetastatic HER2Expansion cohortOral mucositisPrimary endpointSecondary endpointsAntitumor immunityImmune signaturesPrior linesEvaluating the clinical effectiveness and safety of various HER2-targeted regimens after prior taxane/trastuzumab in patients with previously treated, unresectable, or metastatic HER2-positive breast cancer: a systematic review and network meta-analysis
Paracha N, Reyes A, Diéras V, Krop I, Pivot X, Urruticoechea A. Evaluating the clinical effectiveness and safety of various HER2-targeted regimens after prior taxane/trastuzumab in patients with previously treated, unresectable, or metastatic HER2-positive breast cancer: a systematic review and network meta-analysis. Breast Cancer Research And Treatment 2020, 180: 597-609. PMID: 32100144, PMCID: PMC7103014, DOI: 10.1007/s10549-020-05577-7.Peer-Reviewed Original ResearchConceptsMetastatic HER2-positive breast cancerHER2-positive breast cancerOverall response rateProgression-free survivalT-DM1Breast cancerHazard ratioOverall survivalHead trial dataElevated liver transaminasesGastrointestinal side effectsTrial of treatmentAbsence of headRandom-effects NMAAdjuvant therapyEfficacy outcomesLiver transaminasesSafety endpointTolerability profileAdverse eventsEarly relapseMethodsSystematic reviewClinical effectivenessTrastuzumab emtansineConclusionsThe efficacy
2019
A phase Ib, open-label, dose-escalation study of the safety and pharmacology of taselisib (GDC-0032) in combination with either docetaxel or paclitaxel in patients with HER2-negative, locally advanced, or metastatic breast cancer
Abramson VG, Oliveira M, Cervantes A, Wildiers H, Patel MR, Bauer TM, Bedard PL, Becerra C, Richey S, Wei MC, Reyner E, Bond J, Cui N, Wilson TR, Moore HM, Saura C, Krop IE. A phase Ib, open-label, dose-escalation study of the safety and pharmacology of taselisib (GDC-0032) in combination with either docetaxel or paclitaxel in patients with HER2-negative, locally advanced, or metastatic breast cancer. Breast Cancer Research And Treatment 2019, 178: 121-133. PMID: 31368034, DOI: 10.1007/s10549-019-05360-3.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCarcinoma, Non-Small-Cell LungClass I Phosphatidylinositol 3-KinasesDocetaxelFemaleHumansImidazolesLung NeoplasmsMaleMaximum Tolerated DoseMiddle AgedMutationNeoplasm MetastasisOxazepinesPaclitaxelReceptor, ErbB-2Survival AnalysisTreatment OutcomeConceptsNon-small cell lung cancerDose-limiting toxicityMetastatic breast cancerAdverse eventsBreast cancerPhase IbClinical benefit rateDose-expansion studyObjective response ratePhase II doseSerious adverse eventsDose-escalation studyCell lung cancerBenefit-risk profileDays on/2ResultsEighty patientsPrimary endpointSecondary endpointsSafety profileLung cancerBenefit ratePatientsSingle agentResponse rateDocetaxelA 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 lesions