2017
A Phase Ib Study of Alpelisib (BYL719), a PI3Kα-Specific Inhibitor, with Letrozole in ER+/HER2− Metastatic Breast Cancer
Mayer IA, Abramson VG, Formisano L, Balko JM, Estrada MV, Sanders ME, Juric D, Solit D, Berger MF, Won HH, Li Y, Cantley LC, Winer E, Arteaga CL. A Phase Ib Study of Alpelisib (BYL719), a PI3Kα-Specific Inhibitor, with Letrozole in ER+/HER2− Metastatic Breast Cancer. Clinical Cancer Research 2017, 23: 26-34. PMID: 27126994, PMCID: PMC5085926, DOI: 10.1158/1078-0432.ccr-16-0134.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsAromatase InhibitorsBiomarkers, TumorBreast NeoplasmsCell Line, TumorDNA Mutational AnalysisFemaleHumansIn Situ Hybridization, FluorescenceLetrozoleMaximum Tolerated DoseMiddle AgedMutationNeoplasm MetastasisNeoplasm StagingNitrilesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsReceptor, ErbB-2Receptor, Fibroblast Growth Factor, Type 1Receptors, EstrogenThiazolesTreatment OutcomeTriazolesConceptsMaximum-tolerated doseBreast cancer cellsEndocrine therapyClinical benefitCommon drug-related adverse eventsDrug-related adverse eventsMutant breast cancer cellsBreast cancer refractoryPIK3CA mutation statusPIK3CA-mutated tumorsClinical benefit ratePhase Ib studyPI3K catalytic subunit p110αDose-limiting toxicityCancer cellsSelective oral inhibitorOverexpression of FGFR1Combination of letrozoleSynergistic antitumor activityCatalytic subunit p110αCancer refractoryFGFR1/2 amplificationMetastatic ERAdverse eventsObjective response
2016
TransCONFIRM: Identification of a Genetic Signature of Response to Fulvestrant in Advanced Hormone Receptor–Positive Breast Cancer
Jeselsohn R, Barry WT, Migliaccio I, Biagioni C, Zhao J, De Tribolet-Hardy J, Guarducci C, Bonechi M, Laing N, Winer EP, Brown M, Di Leo A, Malorni L. TransCONFIRM: Identification of a Genetic Signature of Response to Fulvestrant in Advanced Hormone Receptor–Positive Breast Cancer. Clinical Cancer Research 2016, 22: 5755-5764. PMID: 27185372, PMCID: PMC5124409, DOI: 10.1158/1078-0432.ccr-16-0148.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, HormonalBreast NeoplasmsDisease-Free SurvivalDouble-Blind MethodEpidermal Growth FactorEstradiolFemaleFulvestrantGene Expression ProfilingHepatocyte Nuclear Factor 3-alphaHumansMiddle AgedPostmenopauseReceptors, EstrogenSignal TransductionTranscription Factor AP-2TranscriptomeConceptsProgression-free survivalBreast cancerPredictive biomarkersCONFIRM studyMetastatic estrogen receptor-positive breast cancerEstrogen receptor-positive breast cancerReceptor-positive breast cancerGene signatureBiologic pathwaysAdvanced breast cancerMetastatic breast cancerMultivariate Cox modelPotential new therapeutic targetEstrogen receptor antagonistNew therapeutic targetsNegative predictive valuePrimary tumor samplesNovel gene signatureMetastatic ERPrimary ERReceptor antagonistFulvestrant treatmentDecreased responseCox modelER levels