Phase Ib dose-escalation trial of taselisib (GDC-0032) in combination with HER2-directed therapies in patients with advanced HER2+ breast cancer
Grinshpun A, Ren S, Graham N, DeMeo M, Wrabel E, Carter J, Tayob N, Pereslete A, Hamilton E, Juric D, Mayer E, Tolaney S, Krop I, Metzger O. Phase Ib dose-escalation trial of taselisib (GDC-0032) in combination with HER2-directed therapies in patients with advanced HER2+ breast cancer. ESMO Open 2024, 9: 103465. PMID: 38833970, PMCID: PMC11179085, DOI: 10.1016/j.esmoop.2024.103465.Peer-Reviewed Original ResearchProgression-free survivalMaximal tolerated doseHER2+ breast cancerAdverse eventsBreast cancerT-DM1Cohort AHuman epidermal growth factor receptor 2-positiveEpidermal growth factor receptor 2-positiveHER2+) breast cancerMedian progression-free survivalAll-grade adverse eventsAssociated with significant toxicityCirculating tumor DNA analysisDevelopment of acquired resistanceHER2-directed regimensHER2-directed therapyAnti-HER2 therapyHER2-targeted therapyPhase Ib studyTumor DNA analysisPI3KDose escalationImprove disease controlOral inhibitorHER2 heterogeneity and treatment response-associated profiles in HER2-positive breast cancer in the NCT02326974 clinical trial
Li Z, Filho O, Viale G, dell'Orto P, Russo L, Goyette M, Kamat A, Yardley D, Abramson V, Arteaga C, Spring L, Chiotti K, Halsey C, Waks A, King T, Lester S, Bellon J, Winer E, Spellman P, Krop I, Polyak K. HER2 heterogeneity and treatment response-associated profiles in HER2-positive breast cancer in the NCT02326974 clinical trial. Journal Of Clinical Investigation 2024, 134: e176454. PMID: 38300710, PMCID: PMC10977978, DOI: 10.1172/jci176454.Peer-Reviewed Original ResearchPathological complete responseHER2-positive breast cancerHER2 heterogeneityBreast cancerEarly-stage HER2-positive breast cancerHER2-targeted therapyPre-treatment tumorsErbB signalingHER2-targeted antibodiesBasal-like featuresHER2 protein levelsStratification of patientsNational Cancer InstituteNeoadjuvant trialsComplete responseResidual tumorT-DM1Copy number heterogeneityTrastuzumab emtansineERBB2 mRNAImmune infiltrationDownstream pathway componentsClinical challengeClinical trialsTumor