2024
Phase I/Ib Trial of Inavolisib Plus Palbociclib and Endocrine Therapy for PIK3CA-Mutated, Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced or Metastatic Breast Cancer
Jhaveri K, Accordino M, Bedard P, Cervantes A, Gambardella V, Hamilton E, Italiano A, Kalinsky K, Krop I, Oliveira M, Schmid P, Saura C, Turner N, Varga A, Cheeti S, Hilz S, Hutchinson K, Jin Y, Royer-Joo S, Peters U, Shankar N, Schutzman J, Juric D. Phase I/Ib Trial of Inavolisib Plus Palbociclib and Endocrine Therapy for PIK3CA-Mutated, Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced or Metastatic Breast Cancer. Journal Of Clinical Oncology 2024, 42: 3947-3956. PMID: 39236276, PMCID: PMC11575912, DOI: 10.1200/jco.24.00110.Peer-Reviewed Original ResearchTreatment-related adverse eventsDrug-drug interactionsPreliminary antitumor activityEndocrine therapyStudy treatmentHuman epidermal growth factor receptor 2-negativeBreast cancerTreatment-related adverse event ratesLack of drug-drug interactionsConfirmed objective response rateLocally advanced/metastatic breast cancerCirculating tumor DNA analysisEffect of study treatmentPK drug-drug interactionsAntitumor activityObjective response ratePhase I/Ib studyHormone receptor-positiveProgression-free survivalAdvanced/metastatic breast cancerTumor DNA analysisBiomarkers of responseMetastatic breast cancerYears of ageReceptor-positive
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 point
2020
Antitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low–Expressing Advanced Breast Cancer: Results From a Phase Ib Study
Modi S, Park H, Murthy RK, Iwata H, Tamura K, Tsurutani J, Moreno-Aspitia A, Doi T, Sagara Y, Redfern C, Krop IE, Lee C, Fujisaki Y, Sugihara M, Zhang L, Shahidi J, Takahashi S. Antitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low–Expressing Advanced Breast Cancer: Results From a Phase Ib Study. Journal Of Clinical Oncology 2020, 38: 1887-1896. PMID: 32058843, PMCID: PMC7280051, DOI: 10.1200/jco.19.02318.Peer-Reviewed Original ResearchConceptsInterstitial lung diseaseHER2-low breast cancerT-DXdBreast cancerTrastuzumab deruxtecanAntitumor activityConfirmed objective response rateTopoisomerase I inhibitor payloadTreatment-emergent adverse eventsHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Breast cancer refractoryIndependent adjudication committeeObjective response ratePhase Ib studyAdvanced breast cancerGrowth factor receptor 2Preliminary antitumor activityIndependent central reviewWithdrawal of consentFactor receptor 2Cancer refractoryEligible patientsMetastatic HER2Unacceptable toxicity
2019
Genomic alterations in breast cancer: level of evidence for actionability according to ESMO Scale for Clinical Actionability of molecular Targets (ESCAT)
Condorelli R, Mosele F, Verret B, Bachelot T, Bedard P, Cortes J, Hyman D, Juric D, Krop I, Bieche I, Saura C, Sotiriou C, Cardoso F, Loibl S, Andre F, Turner N. Genomic alterations in breast cancer: level of evidence for actionability according to ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). Annals Of Oncology 2019, 30: 365-373. PMID: 30715161, DOI: 10.1093/annonc/mdz036.Peer-Reviewed Original ResearchConceptsLevel of evidenceBreast cancerESMO ScaleClinical actionabilityGenomic alterationsMicrosatellite instabilityLarge randomized trialsMolecular targetsBRCA 1/2 mutationsGermline BRCA1/2 mutationsESR1 mutationsPreclinical evidenceNTRK fusionsRandomized trialsPIK3CA mutationsERBB2 mutationsBRCA1/2 mutationsRecurrent genomic alterationsMDM2 amplificationERBB2 amplificationClinical practiceDriver alterationsPTEN lossTumor genomic landscapeAntitumor activityFirst‐in‐human, phase I study of PF‐06647263, an anti‐EFNA4 calicheamicin antibody–drug conjugate, in patients with advanced solid tumors
Garrido‐Laguna I, Krop I, Burris HA, Hamilton E, Braiteh F, Weise AM, Abu‐Khalaf M, Werner TL, Pirie‐Shepherd S, Zopf CJ, Lakshminarayanan M, Holland JS, Baffa R, Hong DS. First‐in‐human, phase I study of PF‐06647263, an anti‐EFNA4 calicheamicin antibody–drug conjugate, in patients with advanced solid tumors. International Journal Of Cancer 2019, 145: 1798-1808. PMID: 30680712, PMCID: PMC6875752, DOI: 10.1002/ijc.32154.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerAdvanced solid tumorsTumor responseSolid tumorsMetastatic triple-negative breast cancerPhase IPhase 2 doseAntitumor activityHuman xenograft tumor modelsAvailable standard therapiesDose-related mannerLimited antitumor activityXenograft tumor modelCommon AEsStable diseaseManageable safetyPartial responsePotent antitumor activityStandard therapyToxicity probability interval methodOvarian cancerBreast cancerPatientsRP2DTumor model
2012
A phase 1 study of weekly dosing of trastuzumab emtansine (T‐DM1) in patients with advanced human epidermal growth factor 2–positive breast cancer
Beeram M, Krop IE, Burris HA, Girish SR, Yu W, Lu MW, Holden SN, Modi S. A phase 1 study of weekly dosing of trastuzumab emtansine (T‐DM1) in patients with advanced human epidermal growth factor 2–positive breast cancer. Cancer 2012, 118: 5733-5740. PMID: 22648179, DOI: 10.1002/cncr.27622.Peer-Reviewed Original ResearchConceptsHER2-positive metastatic breast cancerMetastatic breast cancerAdverse eventsT-DM1Breast cancerTrastuzumab emtansineObjective partial tumor responseTreatment-related adverse eventsClinical benefit rateDose-escalation studyPartial tumor responsePhase 1 studyTotal trastuzumabDose modificationMedian durationWeekly doseWeekly dosingAdditional patientsTumor responseBenefit rateHuman epidermal growth factorEpidermal growth factorPatientsGrowth factorAntitumor activityPhase I safety, pharmacokinetic, and pharmacodynamic study of the oral phosphatidylinositol-3-kinase and mTOR inhibitor BGT226 in patients with advanced solid tumors
Markman B, Tabernero J, Krop I, Shapiro G, Siu L, Chen L, Mita M, Cuero M, Stutvoet S, Birle D, Anak Ö, Hackl W, Baselga J. Phase I safety, pharmacokinetic, and pharmacodynamic study of the oral phosphatidylinositol-3-kinase and mTOR inhibitor BGT226 in patients with advanced solid tumors. Annals Of Oncology 2012, 23: 2399-2408. PMID: 22357447, DOI: 10.1093/annonc/mds011.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsBreast NeoplasmsColonic NeoplasmsDiarrheaFemaleFluorodeoxyglucose F18HumansImidazolesMaleMaximum Tolerated DoseMiddle AgedNauseaPhosphoinositide-3 Kinase InhibitorsProstatic NeoplasmsQuinolinesRadionuclide ImagingRadiopharmaceuticalsTOR Serine-Threonine KinasesTreatment OutcomeYoung AdultConceptsAdvanced solid tumorsPreliminary antitumor activityStable diseaseSystemic exposureAdaptive Bayesian logistic regression modelSolid tumorsPhase I dose-escalation studyI dose-escalation studyFluorodeoxyglucose positron emission tomographyStable metabolic diseaseVariable systemic exposureAntitumor activityDose-escalation studyLow systemic exposurePI3K pathway inhibitionDay three timesLogistic regression modelsAdverse eventsDose escalationFluorodeoxyglucose uptakeRapamycin inhibitorsTumor shrinkagePharmacodynamic studiesComputed tomographyMTOR inhibitors
2009
Mechanisms of trastuzumab resistance in breast cancer.
Tolaney SM, Krop IE. Mechanisms of trastuzumab resistance in breast cancer. Anti-Cancer Agents In Medicinal Chemistry 2009, 9: 348-55. PMID: 19275526, DOI: 10.2174/1871520610909030348.Peer-Reviewed Original ResearchConceptsBreast cancerTrastuzumab resistanceHER2-positive metastatic breast cancerHER2-positive breast cancerDevelopment of trastuzumabOutcomes of patientsTrastuzumab-based therapyMetastatic breast cancerInvasive breast cancerHER2/neu geneHumanized monoclonal antibodyPoor patient outcomesNovel therapeutic agentsPatient outcomesTherapeutic agentsPatientsTrastuzumabCancerMonoclonal antibodiesAntitumor activityNeu genePotential mechanismsOutcomesSignificant improvementExtracellular domain