2020
TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes.
Tung NM, Robson ME, Ventz S, Santa-Maria CA, Nanda R, Marcom PK, Shah PD, Ballinger TJ, Yang ES, Vinayak S, Melisko M, Brufsky A, DeMeo M, Jenkins C, Domchek S, D'Andrea A, Lin NU, Hughes ME, Carey LA, Wagle N, Wulf GM, Krop IE, Wolff AC, Winer EP, Garber JE. TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes. Journal Of Clinical Oncology 2020, 38: 4274-4282. PMID: 33119476, DOI: 10.1200/jco.20.02151.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerObjective response rateProgression-free survivalPoly (ADP-ribose) polymerase (PARP) inhibitorsPhase II studyBreast cancerMutation carriersII studyMedian progression-free survivalNegative metastatic breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Clinical benefit rateHER2-negative diseasePlatinum-refractory diseaseGrowth factor receptor 2Population of patientsFactor receptor 2Homologous recombination-related genesConfirmed responsesEligible patientsMeasurable diseaseSecondary endpointsChemotherapy regimensPrimary endpoint
2016
Phase III Trial Evaluating Letrozole As First-Line Endocrine Therapy With or Without Bevacizumab for the Treatment of Postmenopausal Women With Hormone Receptor–Positive Advanced-Stage Breast Cancer: CALGB 40503 (Alliance)
Dickler MN, Barry WT, Cirrincione CT, Ellis MJ, Moynahan ME, Innocenti F, Hurria A, Rugo HS, Lake DE, Hahn O, Schneider BP, Tripathy D, Carey LA, Winer EP, Hudis CA. Phase III Trial Evaluating Letrozole As First-Line Endocrine Therapy With or Without Bevacizumab for the Treatment of Postmenopausal Women With Hormone Receptor–Positive Advanced-Stage Breast Cancer: CALGB 40503 (Alliance). Journal Of Clinical Oncology 2016, 34: 2602-2609. PMID: 27138575, PMCID: PMC5012690, DOI: 10.1200/jco.2015.66.1595.Peer-Reviewed Original ResearchConceptsProlong progression-free survivalHormone receptor-positive metastatic breast cancerMetastatic breast cancerAddition of bevacizumabMedian PFSMeasurable diseaseOverall survivalGrade 3Breast cancerAnti-vascular endothelial growth factor therapyBevacizumab prolongs progression-free survivalDe novo metastatic breast cancerEndothelial growth factor therapyNovo metastatic breast cancerRole of bevacizumabTrial of letrozoleMedian overall survivalTreatment-related toxicityDisease-free intervalPhase III trialsProgression-free survivalGrowth factor therapyStage breast cancerHazard of progressionLine endocrine therapy
2014
A randomized phase 2 trial comparing efficacy of the combination of the PARP inhibitor olaparib and the antiangiogenic cediranib against olaparib alone in recurrent platinum-sensitive ovarian cancer.
Liu J, Barry W, Birrer M, Lee J, Buckanovich R, Fleming G, Rimel B, Buss M, Nattam S, Hurteau J, Luo W, Quy P, Obermayer E, Whalen C, Lee H, Winer E, Kohn E, Ivy S, Matulonis U. A randomized phase 2 trial comparing efficacy of the combination of the PARP inhibitor olaparib and the antiangiogenic cediranib against olaparib alone in recurrent platinum-sensitive ovarian cancer. Journal Of Clinical Oncology 2014, 32: lba5500-lba5500. DOI: 10.1200/jco.2014.32.18_suppl.lba5500.Peer-Reviewed Original ResearchProgression-free survivalPartial responseComplete responseHazard ratioOvarian cancerRecurrent platinum-sensitive ovarian cancerMedian progression-free survivalPrior anti-angiogenic therapyPARP inhibitorsPlatinum-sensitive ovarian cancerRandomized phase 2 trialOpen-label studyRecurrent ovarian cancerPhase 2 trialPhase 1 studyExploratory subgroup analysisAnti-angiogenic therapyCombination of cediranibPARP inhibitor olaparibMeasurable diseaseRECIST 1.1Radiographic progressionPFS eventsPS 0Oral combinationPhase I trial of olaparib in combination with cisplatin for the treatment of patients with advanced breast, ovarian and other solid tumors
Balmaña J, Tung N, Isakoff S, Graña B, Ryan P, Saura C, Lowe E, Frewer P, Winer E, Baselga J, Garber J. Phase I trial of olaparib in combination with cisplatin for the treatment of patients with advanced breast, ovarian and other solid tumors. Annals Of Oncology 2014, 25: 1656-1663. PMID: 24827126, DOI: 10.1093/annonc/mdu187.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsSolid tumorsBRCA1/2 mutationsDay 1Overall objective response rateBID days 1Grade 3 neutropeniaObjective response ratePhase I trialTreatment of patientsGermline BRCA1/2 mutationsColony-stimulating factorWarrants further investigationAdvanced breastHematologic supportMeasurable diseaseOral olaparibAdverse eventsI trialTreatment cohortsLipase elevationCisplatin dosesFrequent gradePreliminary efficacyStandard treatment
2013
Phase II study of ruxolitinib in patients with pStat3+ breast cancer.
Lin N, Gelman R, Brock J, Bardia A, Mayer E, Overmoyer B, Wang V, Iannone M, Krop I, Polyak K, Winer E. Phase II study of ruxolitinib in patients with pStat3+ breast cancer. Journal Of Clinical Oncology 2013, 31: tps1134-tps1134. DOI: 10.1200/jco.2013.31.15_suppl.tps1134.Peer-Reviewed Original ResearchBreast cancerObjective responseCohort BCohort AOpen-label phase 2 trialIL-6/JAK2/STAT3Tumor tissueM.D. Anderson Symptom InventoryTriple-negative breast cancerAdequate organ functionBaseline tumor biopsiesECOG PS 0High-risk myelofibrosisPhase II studyEORTC QLQ CPhase 2 trialInflammatory breast cancerArchival tumor tissueWk 4JAK2/STAT3Further studiesAccessible diseaseMeasurable diseasePrior therapyPrimary endpoint
2012
CALGB 40502/NCCTG N063H: Randomized phase III trial of weekly paclitaxel (P) compared to weekly nanoparticle albumin bound nab-paclitaxel (NP) or ixabepilone (Ix) with or without bevacizumab (B) as first-line therapy for locally recurrent or metastatic breast cancer (MBC).
Rugo H, Barry W, Moreno-Aspitia A, Lyss A, Cirrincione C, Mayer E, Naughton M, Layman R, Carey L, Somer R, Perez E, Hudis C, Winer E. CALGB 40502/NCCTG N063H: Randomized phase III trial of weekly paclitaxel (P) compared to weekly nanoparticle albumin bound nab-paclitaxel (NP) or ixabepilone (Ix) with or without bevacizumab (B) as first-line therapy for locally recurrent or metastatic breast cancer (MBC). Journal Of Clinical Oncology 2012, 30: cra1002-cra1002. DOI: 10.1200/jco.2012.30.18_suppl.cra1002.Peer-Reviewed Original ResearchProgression-free survivalMetastatic breast cancerNab-paclitaxelPhase III trialsSensory neuropathyHazard ratioIII trialsInterim analysisGrade 2 sensory neuropathyMedian progression-free survivalAlbumin-bound formulationWeekly nanoparticle albuminPrimary end pointFirst-line therapyHormone receptor statusCause deathMeasurable diseaseWeek dosingWeekly paclitaxelHematologic toxicityFree survivalReceptor statusTaxane useExperimental armNanoparticle albuminActivity of cabozantinib (XL184) in metastatic breast cancer (MBC): Results from a phase II randomized discontinuation trial (RDT).
Winer E, Tolaney S, Nechushtan H, Berger R, Kurzrock R, Ron I, Schoffski P, Awada A, Yasenchak C, Burris H, Ramies D, Rafferty T, Shen X. Activity of cabozantinib (XL184) in metastatic breast cancer (MBC): Results from a phase II randomized discontinuation trial (RDT). Journal Of Clinical Oncology 2012, 30: 535-535. DOI: 10.1200/jco.2012.30.15_suppl.535.Peer-Reviewed Original ResearchProgression-free survivalMetastatic breast cancerBone scanTumor regressionWk 12Common grade 3/4 AEsMedian progression-free survivalPost-baseline tumour assessmentActivity of cabozantinibGrade 5 AEsMedian age 56Median prior linesObjective response rateObjective tumor regressionStudy days 1Breast cancer developmentDysregulation of METBone painEligible patientsEvaluable ptsMeasurable diseasePrior anthracyclineSerum NTxImproved painPrimary endpoint
2009
Use of BIBW 2992, a Novel Irreversible EGFR/HER1 and HER2 Tyrosine Kinase Inhibitor To Treat Patients with HER2-Positive Metastatic Breast Cancer after Failure of Treatment with Trastuzumab.
Hickish T, Wheatley D, Lin N, Carey L, Houston S, Mendelson D, Solca F, Uttenreuther-Fischer M, Jones H, Winer E. Use of BIBW 2992, a Novel Irreversible EGFR/HER1 and HER2 Tyrosine Kinase Inhibitor To Treat Patients with HER2-Positive Metastatic Breast Cancer after Failure of Treatment with Trastuzumab. Cancer Research 2009, 69: 5060-5060. DOI: 10.1158/0008-5472.sabcs-09-5060.Peer-Reviewed Original ResearchHER2-positive metastatic breast cancerEpidermal growth factor receptorPhase II studyMetastatic breast cancerBIBW 2992Partial responseBreast cancerGrowth factor receptorII studyEastern Cooperative Oncology Group performance statusSingle-arm phase II studyHER2-positive breast cancer patientsTrastuzumab-resistant cell linesHER2-positive breast cancerHER2 tyrosine kinase inhibitorAdequate organ functionCutaneous adverse eventsEarly clinical responseObjective response rateFactor receptorBreast cancer patientsFailure of treatmentTyrosine kinase inhibitorsEligible patientsMeasurable diseaseA phase I study of an autologous GM-CSF-secreting breast cancer vaccine.
Anderson K, Hodi F, Sasada T, Canning C, Hassett M, Mayer E, Hannagan K, Wong J, Colson Y, Shoji B, Najita J, Sibani S, LaBaer J, Winer E, Dranoff G. A phase I study of an autologous GM-CSF-secreting breast cancer vaccine. Cancer Research 2009, 69: 4124. DOI: 10.1158/0008-5472.sabcs-4124.Peer-Reviewed Original ResearchBreast cancer vaccinesGM-CSFAutologous GM-CSFCancer vaccinesLung cancerSkin biopsiesImmune responseECOG performance status 0Antigen-specific immune responsesLocal injection site reactionsPerformance status 0Anti-tumor immunityInjection site reactionsMetastatic breast cancerMalignant pleural effusionReplication-defective adenoviral vectorMultiple tumor modelsGM-CSF secretionBreast cancer cellsTumor cell yieldGranulocyte-macrophage colonyAutologous vaccinationMeasurable diseasePrior chemotherapyStable diseaseA phase I study of vandetanib and metronomic chemotherapy in advanced breast cancer.
Mayer E, Isakoff S, Hannagan K, Savoie J, Beckman J, Klement G, Gelman R, Winer E, Burstein H. A phase I study of vandetanib and metronomic chemotherapy in advanced breast cancer. Cancer Research 2009, 69: 906. DOI: 10.1158/0008-5472.sabcs-906.Peer-Reviewed Original ResearchAdvanced breast cancerDose-escalation cohortsAbnormal hepatic functionVascular endothelial growth factorBreast cancerMetronomic chemotherapyHepatic functionContinuous low-dose oral cyclophosphamideLow-dose oral cyclophosphamideSequential dose-escalation cohortsStage IV breast cancerOral tyrosine kinase inhibitorGrade 3 eventsOral combination therapyPrior chemotherapy regimensStable brain metastasesModest clinical activityAnti-angiogenic treatmentTyrosine kinase inhibitorsEndothelial growth factorEpidermal growth factor receptorEligible patientsGrowth factor receptorMeasurable diseaseModerate hypertension
2006
Rebeccamycin analog for refractory breast cancer: A randomized phase II trial of dosing schedules
Burstein HJ, Overmoyer B, Gelman R, Silverman P, Savoie J, Clarke K, Dumadag L, Younger J, Ivy P, Winer EP. Rebeccamycin analog for refractory breast cancer: A randomized phase II trial of dosing schedules. Investigational New Drugs 2006, 25: 161-164. PMID: 16969707, DOI: 10.1007/s10637-006-9007-6.Peer-Reviewed Original ResearchConceptsAdvanced breast cancerDifferent treatment schedulesBreast cancerTreatment scheduleAdjuvant chemotherapyArm 2Arm 1Response rateAnthracycline-based adjuvant chemotherapyRefractory advanced breast cancerRandomized phase II trialPrior chemotherapy regimensRefractory breast cancerModest clinical activityPhase II trialPrimary study endpointMetastatic breast cancerCentral venous accessAnemia 5Eligible patientsMeasurable diseaseNausea/Prior chemotherapyStable diseaseChemotherapy regimensTrastuzumab and vinorelbine or taxane chemotherapy for HER2+ metastatic breast cancer: The TRAVIOTA study
Burstein H, Keshaviah A, Baron A, Hart R, Lambert-Falls R, Marcom P, Gelman R, Winer E. Trastuzumab and vinorelbine or taxane chemotherapy for HER2+ metastatic breast cancer: The TRAVIOTA study. Journal Of Clinical Oncology 2006, 24: 650-650. DOI: 10.1200/jco.2006.24.18_suppl.650.Peer-Reviewed Original ResearchMetastatic breast cancerAdvanced breast cancerBreast cancerTaxane chemotherapyResponse rateMore frequent grade 3Stage IV breast cancerComparable clinical activityFrequent grade 3Protocol-based therapySide effect profileHigh response rateDose delaysEligible patientsMeasurable diseasePrior chemotherapyVinorelbine therapyWeekly taxanesWeekly vinorelbineChemotherapy regimenPrimary endpointTaxane therapyHematological toxicityEffect profileClinical trialsPhase II trial of lapatinib for brain metastases in patients with HER2+ breast cancer
Lin N, Carey L, Liu M, Younger J, Come S, Bullitt E, Van Den Abbeele A, Li X, Hochberg F, Winer E. Phase II trial of lapatinib for brain metastases in patients with HER2+ breast cancer. Journal Of Clinical Oncology 2006, 24: 503-503. DOI: 10.1200/jco.2006.24.18_suppl.503.Peer-Reviewed Original ResearchBrain metastasesBreast cancerObjective responsePrimary endpointCNS lesionsCNS diseaseCentral nervous system metastasesVolumetric declinesCentral radiology reviewProgressive brain metastasesNervous system metastasesPhase II trialEfficacy of lapatinibMetastatic breast cancerFDG-PET scansMean age 52Analysis of QOLCommon AEsEligible patientsMeasurable diseasePo bidII trialPrior radiationRECIST criteriaSecondary endpoints
2005
Isolated central nervous system metastases in patients with HER2-overexpressing advanced breast cancer treated with first-line trastuzumab-based therapy
Burstein HJ, Lieberman G, Slamon DJ, Winer EP, Klein P. Isolated central nervous system metastases in patients with HER2-overexpressing advanced breast cancer treated with first-line trastuzumab-based therapy. Annals Of Oncology 2005, 16: 1772-1777. PMID: 16150805, DOI: 10.1093/annonc/mdi371.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCentral Nervous System NeoplasmsCyclophosphamideDisease ProgressionDoxorubicinFemaleFollow-Up StudiesGene AmplificationHumansIn Situ Hybridization, FluorescencePaclitaxelPrevalenceReceptor, ErbB-2Survival RateTime FactorsTrastuzumabVinblastineVinorelbineConceptsTrastuzumab-based therapyMetastatic breast cancerHER2-overexpressing metastatic breast cancerCentral nervous system metastasesNervous system metastasesBreast cancerCNS progressionCNS metastasesFirst-line trastuzumab-based therapyHER2-positive metastatic breast cancerMulticenter phase II trialAdvanced breast cancerFirst-line treatmentPhase II trialPhase III studyTrastuzumab-based treatmentPrimary breast cancerHER2 gene amplificationGene amplificationMeasurable diseaseCNS recurrenceII trialIII studyMetastatic diseasePatient survival
2000
A randomized study comparing standard versus moderately high dose megestrol acetate for patients with advanced prostate carcinoma
Dawson N, Conaway M, Halabi S, Winer E, Small E, Lake D, Vogelzang N. A randomized study comparing standard versus moderately high dose megestrol acetate for patients with advanced prostate carcinoma. Cancer 2000, 88: 825-834. PMID: 10679652, DOI: 10.1002/(sici)1097-0142(20000215)88:4<825::aid-cncr13>3.0.co;2-n.Peer-Reviewed Original ResearchConceptsHormone-refractory prostate carcinomaMegestrol acetateProstate carcinomaStable diseasePartial responsePerformance statusDay doseHigh-dose megestrol acetateEnd pointPossible dose-response effectDose megestrol acetateHigher baseline PSAOral megestrol acetateHigh-dose therapyPoor performance statusPrimary end pointSecondary end pointsMedian survival timeAdvanced prostate carcinomaDose-response effectDose-response correlationEvaluable diseaseMeasurable diseaseDose therapyBaseline PSA
1996
Continuous infusion 5-fluorouracil as first-line therapy for metastatic breast cancer.
Chu L, Sutton LM, Peterson BL, Havlin KA, Winer EP. Continuous infusion 5-fluorouracil as first-line therapy for metastatic breast cancer. The Journal Of Infusional Chemotherapy 1996, 6: 211-6. PMID: 9229318.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerSymptom Distress ScaleFunctional Living Index-CancerFirst-line settingFirst-line therapyBreast cancerContinuous infusionDisease progressionPrevious phase II studyRefractory metastatic breast cancerAdequate bone marrowContinuous infusion fluorouracilGrade 3 mucositisECOG performance statusMedian overall survivalObjective response ratePhase II studyContinuous intravenous infusionQuality of lifeEvaluable diseaseFLIC scoresInfusion fluorouracilMeasurable diseasePrior chemotherapyIndex cancer