2024
Completion Rate and Positive Results Reporting Among Immunotherapy Trials in Breast Cancer, 2004-2023
Mariani M, Viale G, Galbardi B, Licata L, Bosi C, Dugo M, Notini G, Naldini M, Callari M, Criscitiello C, Pusztai L, Bianchini G. Completion Rate and Positive Results Reporting Among Immunotherapy Trials in Breast Cancer, 2004-2023. JAMA Network Open 2024, 7: e2423390. PMID: 39028669, PMCID: PMC11259908, DOI: 10.1001/jamanetworkopen.2024.23390.Peer-Reviewed Original ResearchConceptsCross-sectional studyPhase III trialsIII trialsBreast cancerImmunotherapy trialsLandscape of breast cancerPhase II studyPhase II trialPhase I trialSingle-center studySingle-center trialCancer immunotherapy trialsBreast cancer trialsPatient confidenceMain OutcomesFisher's exact testImmuno-oncology trialsTrial featuresProportion of trialsCompletion ratesAdjuvant settingPhase IIReport outcomesII trialPositive results
2021
Neoadjuvant durvalumab plus weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide in triple-negative breast cancer
Foldi J, Silber A, Reisenbichler E, Singh K, Fischbach N, Persico J, Adelson K, Katoch A, Horowitz N, Lannin D, Chagpar A, Park T, Marczyk M, Frederick C, Burrello T, Ibrahim E, Qing T, Bai Y, Blenman K, Rimm DL, Pusztai L. Neoadjuvant durvalumab plus weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide in triple-negative breast cancer. Npj Breast Cancer 2021, 7: 9. PMID: 33558513, PMCID: PMC7870853, DOI: 10.1038/s41523-021-00219-7.Peer-Reviewed Original ResearchStromal tumor-infiltrating lymphocytesWeekly nab-paclitaxelTriple-negative breast cancerPD-L1Nab-paclitaxelAdverse eventsBreast cancerGrade 3/4 treatment-related adverse eventsPhase I/II trialGrade 3/4 adverse eventsTreatment-related adverse eventsDoxorubicin/cyclophosphamidePhase II studyGuillain-Barre syndromeMononuclear inflammatory cellsPathologic complete responseTumor-infiltrating lymphocytesTumor cell stainingEvaluable patientsNeoadjuvant durvalumabSP263 antibodyII trialNeoadjuvant chemotherapyNeoadjuvant therapyPrimary endpoint
2020
EV-202: A phase II study of enfortumab vedotin in patients with select previously treated locally advanced or metastatic solid tumors.
Bruce J, Pusztai L, Braiteh F, Gorla S, Wu C, Baranda J. EV-202: A phase II study of enfortumab vedotin in patients with select previously treated locally advanced or metastatic solid tumors. Journal Of Clinical Oncology 2020, 38: tps3647-tps3647. DOI: 10.1200/jco.2020.38.15_suppl.tps3647.Peer-Reviewed Original ResearchNon-small cell lung cancerSafety/tolerabilityUrothelial carcinomaNectin-4Gastroesophageal cancerBreast cancerOpen-label phase 2 studySolid tumorsDose reduction/interruptionMonoclonal antibody-drug conjugatesActive CNS metastasesHigh-dose steroidsReduction/interruptionTumor-specific cohortsUncontrolled diabetes mellitusDisease control rateMetastatic urothelial carcinomaObjective response ratePhase II studyPlatinum-containing chemotherapyPhase 2 studyMetastatic solid tumorsPD-L1 inhibitorsTreatment of adultsCell lung cancer
2018
Phase II Study of Taselisib (GDC-0032) in Combination with Fulvestrant in Patients with HER2-Negative, Hormone Receptor–Positive Advanced Breast Cancer
Dickler MN, Saura C, Richards DA, Krop IE, Cervantes A, Bedard PL, Patel MR, Pusztai L, Oliveira M, Cardenas AK, Cui N, Wilson TR, Stout TJ, Wei MC, Hsu JY, Baselga J. Phase II Study of Taselisib (GDC-0032) in Combination with Fulvestrant in Patients with HER2-Negative, Hormone Receptor–Positive Advanced Breast Cancer. Clinical Cancer Research 2018, 24: 4380-4387. PMID: 29793946, PMCID: PMC6139036, DOI: 10.1158/1078-0432.ccr-18-0613.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsClass I Phosphatidylinositol 3-KinasesDisease-Free SurvivalDrug-Related Side Effects and Adverse ReactionsFemaleFulvestrantHumansImidazolesMiddle AgedMutationOxazepinesReceptor, ErbB-2Receptors, EstrogenConceptsAdverse eventsClinical activityBreast cancerMutation statusOpen-label phase II studyHR-positive breast cancerHigher objective response rateConfirmatory phase III trialNCI CTCAE v4.0Median treatment durationObjective response ratePhase II studySerious adverse eventsNew safety signalsPhase III trialsPositive breast cancerClin Cancer ResIntramuscular fulvestrantMeasurable diseaseRECIST v1.1II studyIII trialsPostmenopausal womenUnacceptable toxicityTumor response
2017
Pathologic complete response (pCR) rates after neoadjuvant pertuzumab (P) and trastuzumab (H) administered concomitantly with weekly paclitaxel (T) and 5-fluorouracil/epirubicin/cyclophosphamide (FEC) chemotherapy for clinical stage I-III HER2-positive breast cancer.
Foldi J, Mougalian S, Silber A, Lannin D, Killelea B, Chagpar A, Horowitz N, Frederick C, Rispoli L, Abu-Khalaf M, Sabbath K, Sanft T, Fischbach N, Brandt D, Hofstatter E, DiGiovanna M, Pusztai L. Pathologic complete response (pCR) rates after neoadjuvant pertuzumab (P) and trastuzumab (H) administered concomitantly with weekly paclitaxel (T) and 5-fluorouracil/epirubicin/cyclophosphamide (FEC) chemotherapy for clinical stage I-III HER2-positive breast cancer. Journal Of Clinical Oncology 2017, 35: 577-577. DOI: 10.1200/jco.2017.35.15_suppl.577.Peer-Reviewed Original ResearchPathologic complete response rateHER2-positive breast cancerDual HER2 blockadeComplete response ratePCR rateEstrogen receptorHER2 blockadeBreast cancerStage IResponse rateGrade 3/4 adverse eventsSymptomatic congestive heart failureClinical stage ICompletion of chemotherapyPhase II studyTaxane-based chemotherapyCongestive heart failureEfficacy of anthracyclinesPositive breast cancerNormal cardiac functionEntire treatment durationER cohortER- cancersNeoadjuvant pertuzumabWeekly paclitaxel
2016
A phase II study of the PI3K inhibitor taselisib (GDC-0032) combined with fulvestrant (F) in patients (pts) with HER2-negative (HER2-), hormone receptor-positive (HR+) advanced breast cancer (BC).
Dickler M, Saura C, Richards D, Krop I, Cervantes A, Bedard P, Patel M, Pusztai L, Oliveira M, Ware J, Jin H, Wilson T, Stout T, Wei M, Hsu J, Baselga J. A phase II study of the PI3K inhibitor taselisib (GDC-0032) combined with fulvestrant (F) in patients (pts) with HER2-negative (HER2-), hormone receptor-positive (HR+) advanced breast cancer (BC). Journal Of Clinical Oncology 2016, 34: 520-520. DOI: 10.1200/jco.2016.34.15_suppl.520.Peer-Reviewed Original ResearchPembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study
Nanda R, Chow LQ, Dees EC, Berger R, Gupta S, Geva R, Pusztai L, Pathiraja K, Aktan G, Cheng JD, Karantza V, Buisseret L. Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study. Journal Of Clinical Oncology 2016, 34: 2460-2467. PMID: 27138582, PMCID: PMC6816000, DOI: 10.1200/jco.2015.64.8931.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerAdvanced triple-negative breast cancerPD-L1Antitumor activityBreast cancerCell death protein 1 (PD-1) inhibitorsSingle-agent phase II studyAdvanced PD-L1Single-agent pembrolizumabStudy of immunotherapyTreatment-related deathsImmune checkpoint inhibitionPhase Ib studyPhase Ib trialPhase II studyAcceptable safety profilePD-L1 expressionOverall response rateProtein 1 inhibitorCommon toxicitiesIb trialKEYNOTE-012TNBC cohortII studyMedian duration
2014
Open-label randomized clinical trial of standard neoadjuvant chemotherapy with paclitaxel followed by FEC versus the combination of paclitaxel and everolimus followed by FEC in women with triple receptor-negative breast cancer †
Gonzalez-Angulo AM, Akcakanat A, Liu S, Green MC, Murray JL, Chen H, Palla SL, Koenig KB, Brewster AM, Valero V, Ibrahim NK, Moulder-Thompson S, Litton JK, Tarco E, Moore J, Flores P, Crawford D, Dryden MJ, Symmans WF, Sahin A, Giordano SH, Pusztai L, Do K, Mills GB, Hortobagyi GN, Meric-Bernstam F. Open-label randomized clinical trial of standard neoadjuvant chemotherapy with paclitaxel followed by FEC versus the combination of paclitaxel and everolimus followed by FEC in women with triple receptor-negative breast cancer †. Annals Of Oncology 2014, 25: 1122-1127. PMID: 24669015, PMCID: PMC4037860, DOI: 10.1093/annonc/mdu124.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerPathological complete responseStandard neoadjuvant chemotherapyNeoadjuvant chemotherapyReverse phase protein arrayBreast cancerPrimary triple-negative breast cancerMTOR pathwayReceptor-negative breast cancerTriple receptor-negative breast cancerAddition of everolimusGrade 3 pneumonitisGrade 3/4 stomatitisPI3K/AKT/mTOR pathwayRash/desquamationClinical response rateGrade 3/4 toxicitiesPhase II studyClinical end pointsCombination of paclitaxelAKT/mTOR pathwayDirect antiproliferative activityBreast cancer cellsDownregulation of mTORII study
2007
Pharmacogenomic Predictor Discovery in Phase II Clinical Trials for Breast Cancer
Pusztai L, Anderson K, Hess KR. Pharmacogenomic Predictor Discovery in Phase II Clinical Trials for Breast Cancer. Clinical Cancer Research 2007, 13: 6080-6086. PMID: 17947471, DOI: 10.1158/1078-0432.ccr-07-0809.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsClinical Trials, Phase II as TopicGene Expression ProfilingGene Expression Regulation, NeoplasticHumansIn Situ Hybridization, FluorescenceOligonucleotide Array Sequence AnalysisPharmacogeneticsProbabilityRNA, MessengerTissue DistributionTrastuzumabConceptsPhase II studyPhase II trialII trialII studyBreast cancerTwo-stage phase II trialPhase II clinical trialPhase II trial designPredictors of responseMarker-positive patientsPhase II designUnselected patientsPatient populationClinical trialsTrastuzumab responseInsufficient responseTrial designResponse markersSame drugResponse rateMarker testingPotential predictorsMarker assessmentTrialsPatients
2006
Bortezomib (VELCADE®) in metastatic breast cancer: pharmacodynamics, biological effects, and prediction of clinical benefits
Yang CH, Gonzalez-Angulo AM, Reuben JM, Booser DJ, Pusztai L, Krishnamurthy S, Esseltine D, Stec J, Broglio KR, Islam R, Hortobagyi GN, Cristofanilli M. Bortezomib (VELCADE®) in metastatic breast cancer: pharmacodynamics, biological effects, and prediction of clinical benefits. Annals Of Oncology 2006, 17: 813-817. PMID: 16403809, DOI: 10.1093/annonc/mdj131.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBone NeoplasmsBoronic AcidsBortezomibBreast NeoplasmsDisease ProgressionDisease-Free SurvivalFemaleHumansMaleMaximum Tolerated DoseMiddle AgedPleural NeoplasmsProtease InhibitorsPyrazinesReceptors, EstrogenReceptors, ProgesteroneSoft Tissue NeoplasmsSurvival RateTreatment OutcomeConceptsMetastatic breast cancerBreast cancerPlasma interleukin-6 levelsCommon grade 3Limited clinical activityClinical response ratePhase II studyInterleukin-6 levelsMedian survival timeWeek of restBroad antitumor activityStable diseaseII studyObjective responseSkin rashClinical effectsClinical benefitDisease progressionClinical activityGrade 3Pharmacodynamic dataSurvival timeMean inhibitionSingle agentResponse rate
2005
Phase II study of tariquidar, a selective P‐glycoprotein inhibitor, in patients with chemotherapy‐resistant, advanced breast carcinoma
Pusztai L, Wagner P, Ibrahim N, Rivera E, Theriault R, Booser D, Symmans FW, Wong F, Blumenschein G, Fleming DR, Rouzier R, Boniface G, Hortobagyi GN. Phase II study of tariquidar, a selective P‐glycoprotein inhibitor, in patients with chemotherapy‐resistant, advanced breast carcinoma. Cancer 2005, 104: 682-691. PMID: 15986399, DOI: 10.1002/cncr.21227.Peer-Reviewed Original ResearchConceptsAdministration of tariquidarP-gp expressionSestamibi scanBreast carcinomaSestamibi uptakeP-gp-positive tumorsTaxane-containing chemotherapy regimensDocetaxel-related toxicitiesLimited clinical activityObjective tumor responsePercent of patientsPhase II studyAdvanced breast carcinomaP-glycoprotein inhibitor tariquidarP-glycoprotein inhibitorsMultidrug resistance modulationP-gp transporterMultidrug resistance inhibitorsSame chemotherapyStable diseaseChemotherapy regimenChemotherapy regimensTaxane chemotherapyClinical responseDose modification
2003
Phase II study of pegylated liposomal doxorubicin in combination with gemcitabine in patients with metastatic breast cancer.
Rivera E, Valero V, Arun B, Royce M, Adinin R, Hoelzer K, Walters R, Wade JL, Pusztai L, Hortobagyi GN. Phase II study of pegylated liposomal doxorubicin in combination with gemcitabine in patients with metastatic breast cancer. Journal Of Clinical Oncology 2003, 21: 3249-54. PMID: 12947059, DOI: 10.1200/jco.2003.03.111.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerLiposomal doxorubicinBreast cancerOverall survivalDay 1Median cumulative anthracycline doseLeft ventricular ejection fractionPhase II clinical trialCommon grade 3Cumulative anthracycline doseFrequent nonhematologic toxicitiesPrevious anthracycline exposureHand-foot syndromeMedian overall survivalMedian response durationPhase II studyFront-line therapyVentricular ejection fractionOverall response rateAdjuvant chemotherapyAnthracycline doseAssessable patientsMeasurable diseaseNeutropenic complicationsNonhematologic toxicity
2002
Phase II Study of Weekly Docetaxel and Trastuzumab for Patients With HER-2–Overexpressing Metastatic Breast Cancer
Esteva FJ, Valero V, Booser D, Guerra LT, Murray JL, Pusztai L, Cristofanilli M, Arun B, Esmaeli B, Fritsche HA, Sneige N, Smith TL, Hortobagyi GN. Phase II Study of Weekly Docetaxel and Trastuzumab for Patients With HER-2–Overexpressing Metastatic Breast Cancer. Journal Of Clinical Oncology 2002, 20: 1800-1808. PMID: 11919237, DOI: 10.1200/jco.2002.07.058.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Agents, PhytogenicAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsDisease ProgressionDocetaxelDrug Administration ScheduleFemaleGene Expression Regulation, NeoplasticHumansIn Situ Hybridization, FluorescenceMiddle AgedPaclitaxelReceptor, ErbB-2TaxoidsTime FactorsTrastuzumabTreatment OutcomeUp-RegulationConceptsMetastatic breast cancerOverall response rateWeekly docetaxelBreast cancerPhase II studySecond-line therapyTrastuzumab-based therapyWeek of restExtracellular domain levelsII studyLoading doseMedian timeExcessive tearingFluid retentionECD concentrationsRepetitive dosingWeekly treatmentECD levelsPatientsTrastuzumabActive combinationResponse rateDocetaxelCancerAcute toxicity
2001
Phase II study of weekly docetaxel (Taxotere; txt) and trastuzumab (Herceptin; H) for patients with HER-2 overexpressing (HER2+) metastatic breast cancer (MBC)
Esteva F, Valero V, Booser D, Guerra L, Murray J, Pusztai L, Cristofanilli M, Sneige N, Smith T, Hortobagyi G. Phase II study of weekly docetaxel (Taxotere; txt) and trastuzumab (Herceptin; H) for patients with HER-2 overexpressing (HER2+) metastatic breast cancer (MBC). European Journal Of Cancer 2001, 37: s193. DOI: 10.1016/s0959-8049(01)81198-9.Peer-Reviewed Original Research
1999
Phase II study of mitoxantrone by 14-day continuous infusion with granulocyte colony-stimulating factor (GCSF) support in patients with metastatic breast cancer and limited prior therapy
Pusztai L, Holmes F, Fraschini G, Hortobagyi G. Phase II study of mitoxantrone by 14-day continuous infusion with granulocyte colony-stimulating factor (GCSF) support in patients with metastatic breast cancer and limited prior therapy. Cancer Chemotherapy And Pharmacology 1999, 43: 86-91. PMID: 9923546, DOI: 10.1007/s002800050867.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerGranulocyte colony-stimulating factor supportColony-stimulating factor supportObjective response ratePhase II studyContinuous infusionBreast cancerII studyFactor supportSide effectsResponse rateMajor dose-limiting side effectDose-limiting side effectDiscontinuation of therapySecond-line chemotherapySecond-line regimensPhase II evaluationComplete tumor responseContinuous intravenous infusionMaximal cytotoxic effectLimited antitumor activityAsymptomatic cardiotoxicityPrevious therapyStable diseaseMetastatic disease
1998
Daily Oral Etoposide in Patients With Heavily Pretreated Metastatic Breast Cancer
Pusztai L, Walters R, Valero V, Theriault R, Hortobagyi G. Daily Oral Etoposide in Patients With Heavily Pretreated Metastatic Breast Cancer. American Journal Of Clinical Oncology 1998, 21: 442-446. PMID: 9781596, DOI: 10.1097/00000421-199810000-00004.Peer-Reviewed Original ResearchConceptsGrade 4 toxicityMetastatic breast cancerSignificant hematologic toxicityOral etoposideBreast cancerGrade 2Hematologic toxicityDaily oral etoposideFourth-line agentZubrod performance statusPercent of patientsPhase II studyMajority of patientsGreater thrombocytopeniaNeutropenic feverStable diseasePrevious therapyRadiologic evidenceII studyMedian durationPartial responsePerformance statusMedian ageMore regimensSevere anemia