2022
The oral selective estrogen receptor degrader GDC-0810 (ARN-810) in postmenopausal women with hormone receptor-positive HER2-negative (HR + /HER2 −) advanced/metastatic breast cancer
Bardia A, Mayer I, Winer E, Linden H, Ma C, Parker B, Bellet M, Arteaga C, Cheeti S, Gates M, Chang C, Fredrickson J, Spoerke J, Moore H, Giltnane J, Friedman L, Chow Maneval E, Chan I, Jhaveri K. The oral selective estrogen receptor degrader GDC-0810 (ARN-810) in postmenopausal women with hormone receptor-positive HER2-negative (HR + /HER2 −) advanced/metastatic breast cancer. Breast Cancer Research And Treatment 2022, 197: 319-331. PMID: 36401732, PMCID: PMC9823088, DOI: 10.1007/s10549-022-06797-9.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerSelective estrogen receptor degraderDose escalationESR1 mutationsPostmenopausal womenBreast cancerEstrogen receptorCombination treatmentNon-complete response/non-progressive diseaseAdvanced/Metastatic Breast CancerOral selective estrogen receptor degraderPreliminary anti-tumor activityESR1 mutation statusPhase 2 dosePlasma ctDNA samplesCommon adverse eventsNon-progressive diseaseDose-limiting toxicityHormone-releasing hormoneSelective estrogen receptorAnti-tumor activityStable diseaseAdverse eventsPartial responseProgressive diseasePhase Ib study of pembrolizumab in combination with trastuzumab emtansine for metastatic HER2-positive breast cancer
Waks AG, Keenan TE, Li T, Tayob N, Wulf GM, Richardson ET, Attaya V, Anderson L, Mittendorf EA, Overmoyer B, Winer EP, Krop IE, Agudo J, Van Allen EM, Tolaney SM. Phase Ib study of pembrolizumab in combination with trastuzumab emtansine for metastatic HER2-positive breast cancer. Journal For ImmunoTherapy Of Cancer 2022, 10: e005119. PMID: 36252998, PMCID: PMC9577940, DOI: 10.1136/jitc-2022-005119.Peer-Reviewed Original ResearchConceptsObjective response rateProgression-free survivalMetastatic breast cancerAdverse eventsBreast cancerT-DM1Immune biomarkersTrastuzumab emtansineHER2-positive metastatic breast cancerMetastatic HER2-positive breast cancerGrade 3 adverse eventsMedian progression-free survivalTreatment-related adverse eventsHuman epidermal growth factor receptor 2Cell death ligand 1HER2-positive breast cancerEpidermal growth factor receptor 2Dose-finding cohortPhase 2 dosePhase Ib studyPhase Ib trialAnti-HER2 therapyDose-limiting toxicityGrowth factor receptor 2Immune checkpoint blockadePhase 1b Clinical Trial with Alpelisib plus Olaparib for Patients with Advanced Triple-Negative Breast CancerAlpelisib plus Olaparib for Triple-Negative Breast Cancer
Batalini F, Xiong N, Tayob N, Polak M, Eismann J, Cantley LC, Shapiro GI, Adalsteinsson V, Winer EP, Konstantinopoulos PA, D'Andrea A, Swisher EM, Matulonis UA, Wulf GM, Mayer EL. Phase 1b Clinical Trial with Alpelisib plus Olaparib for Patients with Advanced Triple-Negative Breast CancerAlpelisib plus Olaparib for Triple-Negative Breast Cancer. Clinical Cancer Research 2022, 28: 1493-1499. PMID: 35149538, PMCID: PMC9066379, DOI: 10.1158/1078-0432.ccr-21-3045.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerObjective response rateCirculating-free DNABreast cancerCommon treatment-related grade 3Treatment-related grade 3Longer progression-free survivalRecurrent triple-negative breast cancerHigh-grade serous ovarian cancerPARP inhibitionPhase 1b clinical trialPhase 2 dosePhase 1b trialSecondary end pointsProgression-free survivalRecurrent breast cancerGermline BRCA mutationsImportant prognostic informationSerous ovarian cancerBreast cancer cohortBRCA-mutant tumorsNon-BRCA carriersPI3K inhibitorsEligible patientsExpansion cohort
2021
A Phase 1 Dose-Escalation Trial of Radiation Therapy and Concurrent Cisplatin for Stage II and III Triple-Negative Breast Cancer
Bellon JR, Chen YH, Rees R, Taghian AG, Wong JS, Punglia RS, Shiloh RY, Warren LEG, Krishnan MS, Phillips J, Pretz J, Jimenez R, Macausland S, Pashtan I, Andrews C, Isakoff SJ, Winer EP, Tolaney SM. A Phase 1 Dose-Escalation Trial of Radiation Therapy and Concurrent Cisplatin for Stage II and III Triple-Negative Breast Cancer. International Journal Of Radiation Oncology • Biology • Physics 2021, 111: 45-52. PMID: 33713742, DOI: 10.1016/j.ijrobp.2021.03.002.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerBreast-conserving therapyDose-limiting toxicityBCT cohortRadiation therapyConcurrent cisplatinMastectomy cohortBreast cancerEarly-stage triple-negative breast cancerThree-year disease-free survivalPhase 1 dose-escalation trialStage IILocal-regional recurrence ratePhase 2 doseAdjuvant radiation therapyDisease-free survivalDose-escalation trialPhase 1b trialDose of cisplatinHER2-positive tumorsEligible patientsUrinary infectionAdditional patientsDose escalationRecurrence ratePhase I study of JAK1/2 inhibitor ruxolitinib with weekly paclitaxel for the treatment of HER2-negative metastatic breast cancer
Lynce F, Williams JT, Regan MM, Bunnell CA, Freedman RA, Tolaney SM, Chen WY, Mayer EL, Partridge AH, Winer EP, Overmoyer B. Phase I study of JAK1/2 inhibitor ruxolitinib with weekly paclitaxel for the treatment of HER2-negative metastatic breast cancer. Cancer Chemotherapy And Pharmacology 2021, 87: 673-679. PMID: 33585999, DOI: 10.1007/s00280-021-04245-x.Peer-Reviewed Original ResearchConceptsHER2-negative metastatic breast cancerMetastatic breast cancerBreast cancerWeekly paclitaxelAdvanced diseaseHormone receptor-positive diseaseTriple-negative breast cancerGrade 4/5 toxicitiesMost frequent toxicitiesPhase 2 doseWeekly paclitaxel 80Receptor-positive diseaseDose-escalation designJAK1/2 inhibitor ruxolitinibCombination of ruxolitinibBreast cancer cellsOral ruxolitinibPaclitaxel 80PurposePreclinical studiesChemotherapy regimensFrequent toxicitiesProtocol therapyMethodsEligible patientsThirteen patientsVisceral disease
2020
A phase Ib study of pembrolizumab (pembro) plus trastuzumab emtansine (T-DM1) for metastatic HER2+ breast cancer (MBC).
Waks A, Keenan T, Li T, Tayob N, Wulf G, Richardson E, Mittendorf E, Overmoyer B, Krop I, Winer E, Van Allen E, Agudo J, Tolaney S. A phase Ib study of pembrolizumab (pembro) plus trastuzumab emtansine (T-DM1) for metastatic HER2+ breast cancer (MBC). Journal Of Clinical Oncology 2020, 38: 1046-1046. DOI: 10.1200/jco.2020.38.15_suppl.1046.Peer-Reviewed Original ResearchObjective response rateProgression-free survivalAdverse eventsT-DM1PD-L1 combined positive scoreTumor-infiltrating lymphocyte (TIL) statusClinical benefit rateDose-finding cohortMedian age 54Phase 2 dosePhase Ib studyCombined positive scoreAnti-PD1 antibodyPhase 1 trialDe-escalation designEligible patientsLymphocyte statusMetastatic HER2Expansion cohortOral mucositisPrimary endpointSecondary endpointsAntitumor immunityImmune signaturesPrior lines
2019
Olaparib and α-specific PI3K inhibitor alpelisib for patients with epithelial ovarian cancer: a dose-escalation and dose-expansion phase 1b trial
Konstantinopoulos PA, Barry WT, Birrer M, Westin SN, Cadoo KA, Shapiro GI, Mayer EL, O'Cearbhaill RE, Coleman RL, Kochupurakkal B, Whalen C, Curtis J, Farooq S, Luo W, Eismann J, Buss MK, Aghajanian C, Mills GB, Palakurthi S, Kirschmeier P, Liu J, Cantley LC, Kaufmann SH, Swisher EM, D'Andrea AD, Winer E, Wulf GM, Matulonis UA. Olaparib and α-specific PI3K inhibitor alpelisib for patients with epithelial ovarian cancer: a dose-escalation and dose-expansion phase 1b trial. The Lancet Oncology 2019, 20: 570-580. PMID: 30880072, PMCID: PMC7025391, DOI: 10.1016/s1470-2045(18)30905-7.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Ovarian EpithelialDose-Response Relationship, DrugDrug-Related Side Effects and Adverse ReactionsFemaleGenome, HumanHumansMaximum Tolerated DoseMiddle AgedMutationOvarian NeoplasmsPhosphoinositide-3 Kinase InhibitorsPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsThiazolesTreatment OutcomeConceptsEpithelial ovarian cancerPhase 2 dosePI3K inhibitor alpelisibPrimary peritoneal cancerPhase 1b trialRecurrent breast cancerGermline BRCA mutationsOvarian cancerBreast cancerDose levelsPeritoneal cancerBRCA mutationsFallopian tubeCommon treatment-related grade 3High-grade serous histologyTreatment-related grade 3Breast Cancer Research FoundationDecreased neutrophil countDose-escalation cohortsDose-expansion cohortsTreatment-related deathsTriple negative histologyResponse Evaluation CriteriaSolid Tumors 1.1Key eligibility criteria
2014
Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study
Liu JF, Barry WT, Birrer M, Lee JM, Buckanovich RJ, Fleming GF, Rimel B, Buss MK, Nattam S, Hurteau J, Luo W, Quy P, Whalen C, Obermayer L, Lee H, Winer EP, Kohn EC, Ivy SP, Matulonis UA. Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. The Lancet Oncology 2014, 15: 1207-1214. PMID: 25218906, PMCID: PMC4294183, DOI: 10.1016/s1470-2045(14)70391-2.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Ovarian EpithelialCisplatinConfidence IntervalsDisease-Free SurvivalDose-Response Relationship, DrugDrug Administration ScheduleFemaleFollow-Up StudiesHumansKaplan-Meier EstimateMaximum Tolerated DoseMiddle AgedNeoplasm Recurrence, LocalNeoplasms, Glandular and EpithelialOvarian NeoplasmsPhthalazinesPiperazinesQuinazolinesRisk AssessmentSurvival AnalysisTreatment OutcomeConceptsProgression-free survivalRecurrent platinum-sensitive ovarian cancerPlatinum-sensitive ovarian cancerPhase 2 studyOvarian cancerOlaparib monotherapyMedian progression-free survivalGermline BRCA statusPhase 2 dosePrimary peritoneal cancerRecurrent ovarian cancerPhase 2 trialPhase 3 trialSide effect profilePhase 1 trialUS academic medical centersPatient-reported outcomesEndometrioid ovarian cancerGermline BRCA1/2 mutationsAnti-angiogenic therapyAnti-angiogenic agentsCombination of olaparibAcademic medical centerNational Cancer InstituteVEGF receptor 1