2024
TBCRC 048 (olaparib expanded) expansion cohorts: Phase 2 study of olaparib monotherapy in patients (pts) with metastatic breast cancer (MBC) with germline (g) mutations in PALB2 or somatic (s) mutations in BRCA1 or BRCA2.
Tung N, Robson M, Nanda R, Li T, Vinayak S, Shah P, Khoury K, Kimmick G, Santa-Maria C, Brufsky A, DeMeo M, Vieira J, Carey L, Wulf G, Domchek S, Krop I, Wolff A, Winer E, Garber J. TBCRC 048 (olaparib expanded) expansion cohorts: Phase 2 study of olaparib monotherapy in patients (pts) with metastatic breast cancer (MBC) with germline (g) mutations in PALB2 or somatic (s) mutations in BRCA1 or BRCA2. Journal Of Clinical Oncology 2024, 42: 1021-1021. DOI: 10.1200/jco.2024.42.16_suppl.1021.Peer-Reviewed Original ResearchProgression-free survivalDuration of responseMetastatic breast cancerClinical benefit rateTriple-negative breast cancerMedian duration of responseMedian progression-free survivalMutant allele frequencyExpansion cohortHER2-negativeHER2-positiveCohort 2aNon-respondersBreast cancerEarly due to slow enrollmentMetastatic chemotherapy regimensResponse to olaparibPhase 2 studyPhase II trialKaplan-Meier methodPredictors of responseCohort of womenWilcoxon rank sum testRank sum testBRCA1mTucatinib-trastuzumab-capecitabine for treatment of leptomeningeal metastasis in HER2+ breast cancer: TBCRC049 phase 2 study results.
O'Brien B, Murthy R, Berry D, Singareeka Raghavendra A, Gule-Monroe M, Johnson J, Schwartz-Gomez J, Topletz-Erickson A, Lobbous M, Melisko M, Morikawa A, Ferguson S, de Groot J, Krop I, Valero V, Rimawi M, Wolff A, Tripathy D, Lin N, Stringer-Reasor E. Tucatinib-trastuzumab-capecitabine for treatment of leptomeningeal metastasis in HER2+ breast cancer: TBCRC049 phase 2 study results. Journal Of Clinical Oncology 2024, 42: 2018-2018. DOI: 10.1200/jco.2024.42.16_suppl.2018.Peer-Reviewed Original ResearchHER2+ breast cancerLeptomeningeal metastasesPatient-reported outcomesBreast cancerObjective responseClinical examCSF cytologyEvidence of clinically meaningful benefitHER2-targeted tyrosine kinase inhibitorsMedian time to CNS progressionMetastatic HER2+ breast cancerKarnofsky performance status >Treatment of leptomeningeal metastasesAbnormal CSF cytologyPerformance status >Targeted neurological deficitsMDASI-BTPhase 2 studyTyrosine kinase inhibitorsClinically meaningful benefitPre-specified timepointsPreliminary efficacy dataCNS progressionMedian OSCNS metastases
2023
Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: final 10-year analysis of the open-label, single-arm, phase 2 APT trial
Tolaney S, Tarantino P, Graham N, Tayob N, Parè L, Villacampa G, Dang C, Yardley D, Moy B, Marcom P, Albain K, Rugo H, Ellis M, Shapira I, Wolff A, Carey L, Barroso-Sousa R, Villagrasa P, DeMeo M, DiLullo M, Zanudo J, Weiss J, Wagle N, Partridge A, Waks A, Hudis C, Krop I, Burstein H, Prat A, Winer E. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: final 10-year analysis of the open-label, single-arm, phase 2 APT trial. The Lancet Oncology 2023, 24: 273-285. PMID: 36858723, DOI: 10.1016/s1470-2045(23)00051-7.Peer-Reviewed Original ResearchConceptsHER2-positive breast cancerInvasive disease-free survivalDisease-free survivalRecurrence-free intervalAdjuvant paclitaxelBreast cancerEastern Cooperative Oncology Group performance statusInvasive disease-free survival eventsDisease-free survival eventsHormone receptor-positive diseaseNew contralateral breast cancerBreast cancer-specific survivalProtocol-defined treatmentCancer-specific survivalReceptor-positive diseasePhase 2 studyContralateral breast cancerLong-term outcomesAPT trialCause deathEligible patientsIntravenous paclitaxelTrastuzumab weeklyDistant recurrenceIpsilateral recurrence
2022
Phase 2 trial of tucatinib plus trastuzumab deruxtecan in patients with HER2+ locally advanced or metastatic breast cancer with and without brain metastases (HER2CLIMB-04, trial in progress).
Krop I, Carey L, Ramos J, Chen Y, Hamilton E. Phase 2 trial of tucatinib plus trastuzumab deruxtecan in patients with HER2+ locally advanced or metastatic breast cancer with and without brain metastases (HER2CLIMB-04, trial in progress). Journal Of Clinical Oncology 2022, 40: tps1111-tps1111. DOI: 10.1200/jco.2022.40.16_suppl.tps1111.Peer-Reviewed Original ResearchHuman epidermal growth factor receptor 2Metastatic breast cancerDisease control rateProgression-free survivalDuration of responseBrain metastasesAntibody-drug conjugatesRECIST 1.1Trastuzumab deruxtecanInvestigator assessmentBreast cancerSmall molecule tyrosine kinase inhibitorsTopoisomerase I inhibitor payloadEpidermal growth factor receptor 2Monoclonal antibodiesBreast cancer xenograft modelActive brain metastasesResponse-evaluable patientsManageable safety profileObjective response ratePhase 2 studyPhase 2 trialGrowth factor receptor 2Limited treatment optionsPatient-reported outcomes
2020
Phase 2 study of buparlisib (BKM120), a pan-class I PI3K inhibitor, in patients with metastatic triple-negative breast cancer
Garrido-Castro AC, Saura C, Barroso-Sousa R, Guo H, Ciruelos E, Bermejo B, Gavilá J, Serra V, Prat A, Paré L, Céliz P, Villagrasa P, Li Y, Savoie J, Xu Z, Arteaga CL, Krop IE, Solit DB, Mills GB, Cantley LC, Winer EP, Lin NU, Rodon J. Phase 2 study of buparlisib (BKM120), a pan-class I PI3K inhibitor, in patients with metastatic triple-negative breast cancer. Breast Cancer Research 2020, 22: 120. PMID: 33138866, PMCID: PMC7607628, DOI: 10.1186/s13058-020-01354-y.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAminopyridinesAntineoplastic Combined Chemotherapy ProtocolsClass I Phosphatidylinositol 3-KinasesDisease ProgressionFemaleHigh-Throughput Nucleotide SequencingHumansMiddle AgedMorpholinesNeoplasm MetastasisPatient SafetyProtein Kinase InhibitorsProteomicsResponse Evaluation Criteria in Solid TumorsSurvival RateTreatment OutcomeTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerProgression-free survivalPan-class I PI3K inhibitorMetastatic triple-negative breast cancerStable diseasePhase 2 studyBreast cancerOverall survivalPI3K inhibitorsPI3K pathwayPartial responseComplete responseClinical benefitSingle-arm phase 2 studyTriple-negative metastatic breast cancerMedian progression-free survivalK inhibitorsClinical benefit rateEfficacy of buparlisibK pathwayFrequent adverse eventsMedian overall survivalPercent of patientsMetastatic breast cancerSubset of patientsSingle-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis
Brastianos PK, Lee EQ, Cohen JV, Tolaney SM, Lin NU, Wang N, Chukwueke U, White MD, Nayyar N, Kim A, Alvarez-Breckenridge C, Krop I, Mahar MK, Bertalan MS, Shaw B, Mora JL, Goss N, Subramanian M, Nayak L, Dietrich J, Forst DA, Nahed BV, Batchelor TT, Shih HA, Gerstner ER, Moy B, Lawrence D, Giobbie-Hurder A, Carter SL, Oh K, Cahill DP, Sullivan RJ. Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis. Nature Medicine 2020, 26: 1280-1284. PMID: 32483359, DOI: 10.1038/s41591-020-0918-0.Peer-Reviewed Original ResearchConceptsPrimary endpointOpen-label phase 2 trialDose of pembrolizumabExtracranial disease progressionHigher adverse eventsPercentage of patientsPhase 2 studyPhase 2 trialSolid tumor malignanciesFraction of patientsDefinitive progressionUnacceptable toxicityAdverse eventsOverall survivalPatients 17Leptomeningeal carcinomatosisLeptomeningeal disseminationLung cancerDisease progressionOvarian cancerMetastatic cancerPembrolizumabBreast cancerGrade 3Patients
2019
Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer
Modi S, Saura C, Yamashita T, Park YH, Kim SB, Tamura K, Andre F, Iwata H, Ito Y, Tsurutani J, Sohn J, Denduluri N, Perrin C, Aogi K, Tokunaga E, Im SA, Lee KS, Hurvitz SA, Cortes J, Lee C, Chen S, Zhang L, Shahidi J, Yver A, Krop I. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. New England Journal Of Medicine 2019, 382: 610-621. PMID: 31825192, PMCID: PMC7458671, DOI: 10.1056/nejmoa1914510.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCamptothecinConsolidation ChemotherapyFemaleHumansImmunoconjugatesIntention to Treat AnalysisKaplan-Meier EstimateLung Diseases, InterstitialMiddle AgedProgression-Free SurvivalReceptor, ErbB-2TrastuzumabConceptsHER2-positive metastatic breast cancerMetastatic breast cancerHER2-positive breast cancerProgression-free survivalTrastuzumab deruxtecanInterstitial lung diseaseBreast cancerMedian durationLung diseaseTrastuzumab emtansinePhase 1 dose-finding studyAdvanced HER2-positive breast cancerKey secondary end pointEnd pointPrevious treatmentClinical benefit rateDecreased neutrophil countCommon adverse eventsDisease control rateMedian response durationPrimary end pointSecondary end pointsPhase 2 studySubgroup of patientsDurable antitumor activity
2016
Pictilisib for oestrogen receptor-positive, aromatase inhibitor-resistant, advanced or metastatic breast cancer (FERGI): a randomised, double-blind, placebo-controlled, phase 2 trial
Krop IE, Mayer IA, Ganju V, Dickler M, Johnston S, Morales S, Yardley DA, Melichar B, Forero-Torres A, Lee SC, de Boer R, Petrakova K, Vallentin S, Perez EA, Piccart M, Ellis M, Winer E, Gendreau S, Derynck M, Lackner M, Levy G, Qiu J, He J, Schmid P. Pictilisib for oestrogen receptor-positive, aromatase inhibitor-resistant, advanced or metastatic breast cancer (FERGI): a randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet Oncology 2016, 17: 811-821. PMID: 27155741, PMCID: PMC5524539, DOI: 10.1016/s1470-2045(16)00106-6.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorBreast NeoplasmsDouble-Blind MethodDrug Resistance, NeoplasmEstradiolEstrogen Receptor AntagonistsFemaleFollow-Up StudiesFulvestrantHumansMiddle AgedNeoplasm Recurrence, LocalNeoplasm StagingPrognosisReceptor, ErbB-2Receptors, EstrogenSalvage TherapySurvival RateConceptsProgression-free survivalSerious adverse eventsTreatment-related serious adverse eventsWorse adverse eventsPlacebo groupAdverse eventsNon-measurable diseaseAromatase inhibitor treatmentPIK3CA mutationsBreast cancerDay 1Grade 3Inhibitor treatmentDay 15Cycle 1Median progression-free survivalHER2-negative breast cancerEndocrine-resistant breast cancerPIK3CA-mutated tumorsPhase 2 studyPhase 2 trialMetastatic breast cancerWeeks of treatmentAromatase inhibitor resistanceF Hoffmann-La Roche
2015
Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer
Tolaney SM, Tan S, Guo H, Barry W, Van Allen E, Wagle N, Brock J, Larrabee K, Paweletz C, Ivanova E, Janne P, Overmoyer B, Wright JJ, Shapiro GI, Winer EP, Krop IE. Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer. Investigational New Drugs 2015, 33: 1108-1114. PMID: 26123926, PMCID: PMC4608248, DOI: 10.1007/s10637-015-0269-8.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerTriple-negative breast cancerPhase 2 studyProgression-free survivalBreast cancerPartial responseSingle-arm phase 2 studyResults 22 patientsPhase II studyDaily oral dosingOverall response rateRecent preclinical dataMechanism of actionTivantinib monotherapyMetastatic settingAdverse eventsII studyMethods PatientsPrior linesPreclinical dataOral dosingTivantinibPatientsMET expressionResponse rate