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-positiveETHAN: A phase II study comparing different endocrine therapies for male breast cancer.
Leone J, Ruddy K, Rashid N, Giordano S, Gupta G, Hilsenbeck S, Gucalp A, Walsh E, Sukumar J, Makhlin I, Ortiz-Perez T, Spanheimer P, Calhoun B, Wolff A, Krop I, Thompson A. ETHAN: A phase II study comparing different endocrine therapies for male breast cancer. Journal Of Clinical Oncology 2024, 42: tps632-tps632. DOI: 10.1200/jco.2024.42.16_suppl.tps632.Peer-Reviewed Original ResearchResidual cancer burdenMale breast cancerPreoperative endocrine prognostic indexTranslational Breast Cancer Research ConsortiumBreast cancerEndocrine therapyKi-67Patient-reported outcomesNeoadjuvant phaseArm BAromatase inhibitorsHuman epidermal growth factor receptor 2 (HER2)-negative breast cancerOutcome of endocrine therapyResidual cancer burden indexWindow phaseCyclin-dependent kinase 4/6Ki-67 reductionHormone receptor-positivePhase II studyInflammatory breast cancerLack of clinical trialsPhase II trialHR+/HER2- breast cancerAnti-cancer therapyStandard of care
2023
A Multiparameter Molecular Classifier to Predict Response to Neoadjuvant Lapatinib plus Trastuzumab without Chemotherapy in HER2+ Breast Cancer.
Veeraraghavan J, Gutierrez C, De Angelis C, Davis R, Wang T, Pascual T, Selenica P, Sanchez K, Nitta H, Kapadia M, Pavlick A, Galvan P, Rexer B, Forero-Torres A, Nanda R, Storniolo A, Krop I, Goetz M, Nangia J, Wolff A, Weigelt B, Reis-Filho J, Hilsenbeck S, Prat A, Osborne C, Schiff R, Rimawi M. A Multiparameter Molecular Classifier to Predict Response to Neoadjuvant Lapatinib plus Trastuzumab without Chemotherapy in HER2+ Breast Cancer. Clinical Cancer Research 2023, 29: 3101-3109. PMID: 37195235, PMCID: PMC10923553, DOI: 10.1158/1078-0432.ccr-22-3753.Peer-Reviewed Original ResearchAnti-HER2 therapyBreast cancerDual anti-HER2 therapyPathologic complete response rateEstrogen receptor-positive tumorsPIK3CA mutation statusComplete response rateReceptor-positive tumorsBreast cancer specimensHigh NPVNegative predictive valueEndocrine therapyNeoadjuvant lapatinibNeoadjuvant treatmentTreatment deescalationUnselected patientsClinical trialsCancer specimensMutation statusPatientsPredictive valueResponse rateChemotherapyHER2HER2 proteinER+, HER2− advanced breast cancer treated with taselisib and fulvestrant: genomic landscape and associated clinical outcomes
Chen J, Jacot W, Cortés J, Krop I, Dent S, Harbeck N, De Laurentiis M, Diéras V, Im Y, Stout T, Schimmoller F, Savage H, Hutchinson K, Wilson T. ER+, HER2− advanced breast cancer treated with taselisib and fulvestrant: genomic landscape and associated clinical outcomes. Molecular Oncology 2023, 17: 2000-2016. PMID: 36892268, PMCID: PMC10552898, DOI: 10.1002/1878-0261.13416.Peer-Reviewed Original ResearchConceptsProgression-free survivalBreast cancerShorter progression-free survivalNeurofibromin 1Advanced breast cancerBreast cancer patientsP53 pathway genesPI3K inhibitorsPI3K inhibitionBaseline ctDNAEndocrine therapyClinical outcomesCancer patientsEstrogen receptorCatalytic subunit alphaTumor DNATaselisibK inhibitorsK inhibitionPI3KOutcomesCancerAlterationsGenomic landscapeProtein p53
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 ageCirculating tumor DNA (ctDNA) and late recurrence in high-risk, hormone receptor–positive, HER2-negative breast cancer (CHiRP).
Lipsyc-Sharf M, De Bruin E, Santos K, McEwen R, Stetson D, Patel A, Kirkner G, Hughes M, Tolaney S, Krop I, Knape C, Feger U, Marsico G, Howarth K, Winer E, Lin N, Parsons H. Circulating tumor DNA (ctDNA) and late recurrence in high-risk, hormone receptor–positive, HER2-negative breast cancer (CHiRP). Journal Of Clinical Oncology 2022, 40: 103-103. DOI: 10.1200/jco.2022.40.16_suppl.103.Peer-Reviewed Original ResearchMinimal residual diseaseDistant metastatic recurrenceAdjuvant endocrine therapyWhole-exome sequencingEndocrine therapyMetastatic recurrenceClinical outcomesBreast cancerHormone receptor-positive breast cancerPlasma samplesTumor tissueHER2-negative breast cancerReceptor-positive breast cancerTumor DNACtDNA detectionRegular surveillance imagingStage 3 diseaseCurative intent chemotherapyTime of consentPrimary tumor tissuesCurrent practice standardsSufficient tumor tissueLiquid biopsy testsAdjuvant settingCtDNA dynamics175P Alpelisib (ALP) + endocrine therapy (ET) in patients (pts) with PIK3CA-mutated, hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC): Subgroup analyses from the BYLieve study
Cardoso F, Juric D, Lerebours F, Krop I, Borrego M, Neven P, Park Y, Yardley D, Jhaveri K, Arce C, Gu E, Akdere M, Rugo H. 175P Alpelisib (ALP) + endocrine therapy (ET) in patients (pts) with PIK3CA-mutated, hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC): Subgroup analyses from the BYLieve study. Annals Of Oncology 2022, 33: s206-s207. DOI: 10.1016/j.annonc.2022.03.194.Peer-Reviewed Original Research
2021
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
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 eventsAlliance A011801 (compassHER2 RD): postneoadjuvant T-DM1 + tucatinib/placebo in patients with residual HER2-positive invasive breast cancer
O'Sullivan CC, Ballman KV, McCall L, Kommalapati A, Zemla T, Weiss A, Mitchell M, Blinder V, Tung NM, Irvin WJ, Lee M, Goetz MP, Symmans WF, Borges VF, Krop I, Carey LA, Partridge AH. Alliance A011801 (compassHER2 RD): postneoadjuvant T-DM1 + tucatinib/placebo in patients with residual HER2-positive invasive breast cancer. Future Oncology 2021, 17: 4665-4676. PMID: 34636255, PMCID: PMC8600597, DOI: 10.2217/fon-2021-0753.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAntineoplastic Combined Chemotherapy ProtocolsBrain NeoplasmsBreastBreast NeoplasmsChemoradiotherapy, AdjuvantChemotherapy, AdjuvantClinical Trials, Phase III as TopicDisease-Free SurvivalDouble-Blind MethodFemaleFollow-Up StudiesHumansMastectomyMiddle AgedMulticenter Studies as TopicNeoadjuvant TherapyNeoplasm Recurrence, LocalNeoplasm, ResidualOxazolesPlacebosProspective StudiesPyridinesQuinazolinesRandomized Controlled Trials as TopicReceptor, ErbB-2ConceptsInvasive disease-free survivalDisease-free survivalBrain metastasis-free survivalBreast cancer-free survivalDistant recurrence-free survivalT-DM1Overall survivalResidual diseaseHER2-positive invasive breast cancerAdjuvant T-DM1Cancer-free survivalRecurrence-free survivalInvasive breast cancerMetastasis-free survivalPharmacokinetic end pointsOutcomes of interestQuality of lifeEligible patientsAdjuvant radiotherapyEndocrine therapyNeoadjuvant chemotherapyCorrelative biomarkersCare guidelinesBreast cancerPlacebo
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 eventsPrimary analysis of KAITLIN: A phase III study of trastuzumab emtansine (T-DM1) + pertuzumab versus trastuzumab + pertuzumab + taxane, after anthracyclines as adjuvant therapy for high-risk HER2-positive early breast cancer (EBC).
Harbeck N, Im S, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis P, Gianni L, Swain S, Im Y, De Laurentiis M, Nowecki Z, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer E, Krop I. Primary analysis of KAITLIN: A phase III study of trastuzumab emtansine (T-DM1) + pertuzumab versus trastuzumab + pertuzumab + taxane, after anthracyclines as adjuvant therapy for high-risk HER2-positive early breast cancer (EBC). Journal Of Clinical Oncology 2020, 38: 500-500. DOI: 10.1200/jco.2020.38.15_suppl.500.Peer-Reviewed Original ResearchHER2-positive early breast cancerInvasive disease-free survivalEarly breast cancerPatient-reported outcomesCo-primary endpointsStandard of careT-DM1ITT populationOverall survivalAnthracycline-based chemotherapyOpen-label studyDisease-free survivalPhase III studyWeeks of surgeryHigh-risk populationChemotherapy-associated toxicityAdjuvant taxanesConcurrent trastuzumabEndocrine therapySecondary endpointsAdjuvant radiotherapyAdjuvant therapyIII studyNodal statusMore patients
2018
369TiP PATINA: A randomized, open label, phase III trial to evaluate the efficacy and safety of palbociclib + Anti-HER2 therapy + endocrine therapy (ET) vs. anti-HER2 therapy + ET after induction treatment for hormone receptor positive (HR+)/HER2-positive metastatic breast cancer (MBC)
Loibl S, Metzger O, Mandrekar S, Mundhenke C, Seiler S, Valagussa P, DeMichele A, Lim E, Tripathy D, Winer E, Huang C, Carey L, Francis P, Miller K, Goetz M, Prat A, Loi S, Krop I, Gianni L, Ciruelos E. 369TiP PATINA: A randomized, open label, phase III trial to evaluate the efficacy and safety of palbociclib + Anti-HER2 therapy + endocrine therapy (ET) vs. anti-HER2 therapy + ET after induction treatment for hormone receptor positive (HR+)/HER2-positive metastatic breast cancer (MBC). Annals Of Oncology 2018, 29: viii121. DOI: 10.1093/annonc/mdy272.357.Peer-Reviewed Original Research
2017
324TiP PATINA: A randomized open label phase III trial to evaluate the efficacy and safety of palbociclib + anti HER2 therapy + endocrine therapy vs anti HER2 therapy + endocrine therapy after induction treatment for hormone receptor positive, HER2-positive metastatic breast cancer
Metzger O, Mandrekar S, Ciruelos E, Loibl S, Valagussa P, Demichele A, Lim E, Tripathy D, Winer E, Huang C, Khoeler M, Carey L, Francis P, Miller K, Goel S, Goetz M, Prat A, Loi S, Krop I, Gianni L. 324TiP PATINA: A randomized open label phase III trial to evaluate the efficacy and safety of palbociclib + anti HER2 therapy + endocrine therapy vs anti HER2 therapy + endocrine therapy after induction treatment for hormone receptor positive, HER2-positive metastatic breast cancer. Annals Of Oncology 2017, 28: v107-v108. DOI: 10.1093/annonc/mdx365.087.Peer-Reviewed Original Research
2014
Systemic Therapy for Patients With Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline
Giordano SH, Temin S, Kirshner JJ, Chandarlapaty S, Crews JR, Davidson NE, Esteva FJ, Gonzalez-Angulo AM, Krop I, Levinson J, Lin NU, Modi S, Patt DA, Perez EA, Perlmutter J, Ramakrishna N, Winer EP. Systemic Therapy for Patients With Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline. Journal Of Clinical Oncology 2014, 32: 2078-2099. PMID: 24799465, PMCID: PMC6076031, DOI: 10.1200/jco.2013.54.0948.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAnastrozoleAntibodies, Monoclonal, HumanizedAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsClinical Trials as TopicComorbidityDocetaxelDrug Administration ScheduleEvidence-Based MedicineFemaleHealth Status DisparitiesHealthcare DisparitiesHumansLapatinibLetrozoleMaytansineMolecular Targeted TherapyNitrilesQuinazolinesReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneSocieties, MedicalTaxoidsTrastuzumabTreatment OutcomeTriazolesUnited StatesConceptsAdvanced breast cancerHuman epidermal growth factor receptorSecond-line treatmentProgression-free survivalFirst-line treatmentBreast cancerPFS benefitT-DM1Epidermal growth factor receptorEndocrine therapyGrowth factor receptorSystemic therapyEstrogen receptor-positive/progesterone receptor-positive breast cancerAdvanced human epidermal growth factor receptorHER2-positive advanced breast cancerProgesterone receptor-positive breast cancerClinical Oncology Clinical Practice GuidelineClinical congestive heart failureStandard first-line therapyPositive advanced breast cancerLeft ventricular ejection fractionOncology Clinical Practice GuidelineReceptor-positive breast cancerThird-line settingFirst-line therapy
2010
Advances in Targeting Src in the Treatment of Breast Cancer and Other Solid Malignancies
Mayer EL, Krop IE. Advances in Targeting Src in the Treatment of Breast Cancer and Other Solid Malignancies. Clinical Cancer Research 2010, 16: 3526-3532. PMID: 20634194, DOI: 10.1158/1078-0432.ccr-09-1834.Peer-Reviewed Original ResearchConceptsMultiple solid tumor typesVascular endothelial growth factor receptorEndothelial growth factor receptorEarly phase trialsSolid tumor typesMultiple human malignanciesTargeting SrcEndocrine therapyGrowth factor receptorCombination regimensOngoing trialsFuture trialsSolid malignanciesProstate cancerBreast cancerEstrogen receptorPreclinical studiesAntitumor effectsTumor typesAngiogenesis inhibitorsCell-signaling pathwaysInhibitor dasatinibInvestigation of combinationsHuman malignanciesModest activity