2022
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).
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 ageClinical outcomes with alpelisib (ALP) plus fulvestrant (FUL) after prior treatment (tx) with FUL in patients (pts) with advanced breast cancer (ABC): A real-world (RW) analysis.
O'Shaughnessy J, Woeckel A, Pistilli B, Hegg R, Vahdat L, Vuina D, ZVK P, Smith T, Kim J, Krop I. Clinical outcomes with alpelisib (ALP) plus fulvestrant (FUL) after prior treatment (tx) with FUL in patients (pts) with advanced breast cancer (ABC): A real-world (RW) analysis. Journal Of Clinical Oncology 2022, 40: 1055-1055. DOI: 10.1200/jco.2022.40.16_suppl.1055.Peer-Reviewed Original ResearchAdvanced breast cancerEndocrine-based therapyPIK3CA mutationsMetastatic settingClinical outcomesCyclin-dependent kinase 4/6 inhibitorsDe-identified electronic health record dataHuman epidermal growth factor receptorImmediate prior therapyLines of therapyProgression-free survivalProgression/deathElectronic health record dataDate of deathHealth record dataEpidermal growth factor receptorReal-world analysisGrowth factor receptorNCCN guidelinesPrior chemotherapyPrior therapyMedian durationMedian timeSubsequent therapyClinical benefit
2016
Phase 1b/2a study of trastuzumab emtansine (T-DM1), paclitaxel, and pertuzumab in HER2-positive metastatic breast cancer
Krop IE, Modi S, LoRusso PM, Pegram M, Guardino E, Althaus B, Lu D, Strasak A, Elias A. Phase 1b/2a study of trastuzumab emtansine (T-DM1), paclitaxel, and pertuzumab in HER2-positive metastatic breast cancer. Breast Cancer Research 2016, 18: 34. PMID: 26979312, PMCID: PMC4791863, DOI: 10.1186/s13058-016-0691-7.Peer-Reviewed Original ResearchConceptsClinical benefit ratePhase 1b/2a studyObjective response rateT-DM1Adverse eventsPaclitaxel dosesPeripheral neuropathyBreast cancerHER2-positive advanced breast cancerHER2-positive metastatic breast cancerPhase 2aPhase 1bGrade adverse eventsT-DM1 3.6Advanced breast cancerMetastatic breast cancerDose-escalation approachPre-clinical studiesAnti-tumor activityConclusionsThis regimenExperienced gradeMeasurable diseasePaclitaxel 80Prior therapyResultsThe MTD
2014
NI-23BRAIN BREAST METASTASES RESPOND TO ANTI-ANGIOGENIC THERAPY BY MODES OF VASCULAR NORMALIZATION
Emblem K, Pinho M, Chandra V, Gerstner E, Stufflebeam S, Sorenson G, Harris G, Freedman R, Sohl J, Younger J, Krop I, Winer E, Lin N. NI-23BRAIN BREAST METASTASES RESPOND TO ANTI-ANGIOGENIC THERAPY BY MODES OF VASCULAR NORMALIZATION. Neuro-Oncology 2014, 16: v143-v143. PMCID: PMC4218348, DOI: 10.1093/neuonc/nou264.22.Peer-Reviewed Original ResearchAnti-angiogenic therapyBreast cancerBrain metastasesVascular normalizationTumor perfusionBrain tumorsDay 1Largest contrast-enhancing lesionPerfusion MRIParenchymal brain metastasesMonths of therapyPhase II studyHormone receptor statusMetastatic breast cancerSubset of patientsContrast-enhancing lesionsPrimary brain tumorsAnti-angiogenic effectsOxygen saturation levelsPrior therapyBreast metastasisII studySystemic therapyImproved survivalReceptor status
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
Primary results from EMILIA, a phase III study of trastuzumab emtansine (T-DM1) versus capecitabine (X) and lapatinib (L) in HER2-positive locally advanced or metastatic breast cancer (MBC) previously treated with trastuzumab (T) and a taxane.
Pegram M, Blackwell K, Miles D, Bianchi G, Krop I, Welslau M, Baselga J, Oh D, Dieras V, Guardino E, Olsen S, Fang L, Lu M, Verma S. Primary results from EMILIA, a phase III study of trastuzumab emtansine (T-DM1) versus capecitabine (X) and lapatinib (L) in HER2-positive locally advanced or metastatic breast cancer (MBC) previously treated with trastuzumab (T) and a taxane. Journal Of Clinical Oncology 2012, 30: 98-98. DOI: 10.1200/jco.2012.30.27_suppl.98.Peer-Reviewed Original ResearchMetastatic breast cancerT-DM1End pointProgressive diseaseAdverse eventsCytotoxic agent DM1Primary end pointUnexpected safety signalsPalmar-plantar erythrodysesthesiaPhase III studyFinal PFS analysisRefractory HER2Prior therapyBaseline demographicsIII studyMedian durationRandomized studyPlantar erythrodysesthesiaUnmanageable toxicityDisease characteristicsAdvanced BCTrastuzumab emtansineNovel therapiesSafety signalsBreast cancerPrimary results from EMILIA, a phase III study of trastuzumab emtansine (T-DM1) versus capecitabine (X) and lapatinib (L) in HER2-positive locally advanced or metastatic breast cancer (MBC) previously treated with trastuzumab (T) and a taxane.
Blackwell K, Miles D, Gianni L, Krop I, Welslau M, Baselga J, Pegram M, Oh D, Dieras V, Olsen S, Fang L, Lu M, Guardino E, Verma S. Primary results from EMILIA, a phase III study of trastuzumab emtansine (T-DM1) versus capecitabine (X) and lapatinib (L) in HER2-positive locally advanced or metastatic breast cancer (MBC) previously treated with trastuzumab (T) and a taxane. Journal Of Clinical Oncology 2012, 30: lba1-lba1. DOI: 10.1200/jco.2012.30.18_suppl.lba1.Peer-Reviewed Original ResearchMetastatic breast cancerT-DM1End pointProgressive diseaseAdverse eventsCytotoxic agent DM1Primary end pointUnexpected safety signalsPalmar-plantar erythrodysesthesiaPhase III studyFinal PFS analysisRefractory HER2Prior therapyBaseline demographicsIII studyMedian durationRandomized studyPlantar erythrodysesthesiaUnmanageable toxicityDisease characteristicsAdvanced BCTrastuzumab emtansineNovel therapiesSafety signalsBreast cancerClinical pharmacology of trastuzumab emtansine (T-DM1): an antibody–drug conjugate in development for the treatment of HER2-positive cancer
Girish S, Gupta M, Wang B, Lu D, Krop IE, Vogel CL, Burris III HA, LoRusso PM, Yi JH, Saad O, Tong B, Chu YW, Holden S, Joshi A. Clinical pharmacology of trastuzumab emtansine (T-DM1): an antibody–drug conjugate in development for the treatment of HER2-positive cancer. Cancer Chemotherapy And Pharmacology 2012, 69: 1229-1240. PMID: 22271209, PMCID: PMC3337408, DOI: 10.1007/s00280-011-1817-3.Peer-Reviewed Original ResearchConceptsSingle-agent T-DM1Anti-therapeutic antibodiesT-DM1 exposureTotal trastuzumabT-DM1Positive metastatic breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Standard noncompartmental approachT-DM1 pharmacokineticsGrowth factor receptor 2Key adverse eventsMetastatic breast cancerHER2-positive cancersStable thioether linkerConcentrations of transaminasesFactor receptor 2Enzyme-linked immunosorbent assayEnzyme-linked immunosorbentHER2 extracellular domainAntibody-drug conjugatesEvaluable patientsPrior therapyClinical responseAdverse events