2019
IMpassion130: Expanded safety analysis from a P3 study of atezolizumab (A) + nab-paclitaxel (nP) in patients (pts) with treatment (tx)-naïve, locally advanced or metastatic triple-negative breast cancer (mTNBC).
Schneeweiss A, Rugo H, Winer E, Barrios C, Iwata H, Dieras V, Loi S, Maiya V, Bond J, Lei G, Chui S, Adams S, Emens L, Schmid P. IMpassion130: Expanded safety analysis from a P3 study of atezolizumab (A) + nab-paclitaxel (nP) in patients (pts) with treatment (tx)-naïve, locally advanced or metastatic triple-negative breast cancer (mTNBC). Journal Of Clinical Oncology 2019, 37: 1068-1068. DOI: 10.1200/jco.2019.37.15_suppl.1068.Peer-Reviewed Original ResearchMetastatic triple-negative breast cancerTriple-negative breast cancerTolerable safety profileCauses of withdrawalMonotherapy trialsPFS benefitSerious AEsSystemic corticosteroidsMedian FUSecondary endpointsNab-paclitaxelAdverse eventsPD-L1Peripheral neuropathyMedian timeSafety profileLonger FUSafety signalsBreast cancerSafety dataCumulative toxicityData cutAESIP3 studiesGr 3
2017
Kinetic-Pharmacodynamic Model of Chemotherapy-Induced Peripheral Neuropathy in Patients with Metastatic Breast Cancer Treated with Paclitaxel, Nab-Paclitaxel, or Ixabepilone: CALGB 40502 (Alliance)
Mehrotra S, Sharma MR, Gray E, Wu K, Barry WT, Hudis C, Winer EP, Lyss AP, Toppmeyer DL, Moreno-Aspitia A, Lad TE, Valasco M, Overmoyer B, Rugo H, Ratain MJ, Gobburu JV. Kinetic-Pharmacodynamic Model of Chemotherapy-Induced Peripheral Neuropathy in Patients with Metastatic Breast Cancer Treated with Paclitaxel, Nab-Paclitaxel, or Ixabepilone: CALGB 40502 (Alliance). The AAPS Journal 2017, 19: 1411-1423. PMID: 28620884, PMCID: PMC5711539, DOI: 10.1208/s12248-017-0101-9.Peer-Reviewed Original ResearchConceptsChemotherapy-induced peripheral neuropathyProportion of patientsMetastatic breast cancerKinetic-pharmacodynamic modelIndirect response modelNab-paclitaxelDose modificationPeripheral neuropathyBreast cancerDrug effectsRandomized phase III trialLinear drug effectFirst-line chemotherapyPhase III trialsTime pointsDose-limiting toxicityLater time pointsEarly time pointsCALGB 40502Neurotoxicity ScaleIII trialsFunctional assessmentChemotherapeutic agentsPatientsCancer
2015
Randomized Phase III Trial of Paclitaxel Once Per Week Compared With Nanoparticle Albumin-Bound Nab-Paclitaxel Once Per Week or Ixabepilone With Bevacizumab As First-Line Chemotherapy for Locally Recurrent or Metastatic Breast Cancer: CALGB 40502/NCCTG N063H (Alliance)
Rugo HS, Barry WT, Moreno-Aspitia A, Lyss AP, Cirrincione C, Leung E, Mayer EL, Naughton M, Toppmeyer D, Carey LA, Perez EA, Hudis C, Winer EP. Randomized Phase III Trial of Paclitaxel Once Per Week Compared With Nanoparticle Albumin-Bound Nab-Paclitaxel Once Per Week or Ixabepilone With Bevacizumab As First-Line Chemotherapy for Locally Recurrent or Metastatic Breast Cancer: CALGB 40502/NCCTG N063H (Alliance). Journal Of Clinical Oncology 2015, 33: 2361-2369. PMID: 26056183, PMCID: PMC4500830, DOI: 10.1200/jco.2014.59.5298.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAlbuminsAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabBreast NeoplasmsDrug Administration ScheduleEpothilonesFemaleHumansMiddle AgedNanoparticlesNeoplasm MetastasisNeoplasm Recurrence, LocalPaclitaxelTreatment OutcomeConceptsAdvanced breast cancerProgression-free survivalNab-paclitaxelBreast cancerInterim analysisMedian progression-free survivalRandomized phase III trialEarly dose reductionSecond interim analysisFirst-line therapyPhase III trialsMetastatic breast cancerFirst interim analysisEligible patientsLine chemotherapyNonhematologic toxicityPalliative chemotherapyHazard ratioIII trialsOverall survivalPeripheral neuropathyTreatment failureExperimental armLocally RecurrentArm C
2014
Phase I/II study of pilaralisib (SAR245408) in combination with trastuzumab or trastuzumab plus paclitaxel in trastuzumab-refractory HER2-positive metastatic breast cancer
Tolaney S, Burris H, Gartner E, Mayer IA, Saura C, Maurer M, Ciruelos E, Garcia AA, Campana F, Wu B, Xu Y, Jiang J, Winer E, Krop I. Phase I/II study of pilaralisib (SAR245408) in combination with trastuzumab or trastuzumab plus paclitaxel in trastuzumab-refractory HER2-positive metastatic breast cancer. Breast Cancer Research And Treatment 2014, 149: 151-161. PMID: 25537644, DOI: 10.1007/s10549-014-3248-4.Peer-Reviewed Original ResearchConceptsHER2-positive metastatic breast cancerMetastatic breast cancerAdverse eventsBreast cancerArm 2Arm 1Phase I/II dose-escalation studyMetastatic HER2-positive breast cancerPhase I/II studyTreatment-related adverse eventsHER2-positive breast cancerTreatment-related gradeAcceptable safety profileDose-escalation studyDose-limiting toxicityDose-escalation designPan-class IEvaluable patientsPaclitaxel armPrior taxanePrior trastuzumabErythematous rashII studyPartial responsePeripheral neuropathyPolygenic inheritance of paclitaxel-induced sensory peripheral neuropathy driven by axon outgrowth gene sets in CALGB 40101 (Alliance)
Chhibber A, Mefford J, Stahl EA, Pendergrass SA, Baldwin RM, Owzar K, Li M, Winer EP, Hudis CA, Zembutsu H, Kubo M, Nakamura Y, McLeod HL, Ratain MJ, Shulman LN, Ritchie MD, Plenge RM, Witte JS, Kroetz DL. Polygenic inheritance of paclitaxel-induced sensory peripheral neuropathy driven by axon outgrowth gene sets in CALGB 40101 (Alliance). The Pharmacogenomics Journal 2014, 14: 336-342. PMID: 24513692, PMCID: PMC4111770, DOI: 10.1038/tpj.2014.2.Peer-Reviewed Original ResearchConceptsSensory peripheral neuropathyPaclitaxel-induced peripheral neuropathyPeripheral neuropathyCALGB 40101Common dose-limiting toxicityPhase III clinical trialsPaclitaxel-induced neuropathyDose-limiting toxicityAxon outgrowthPaclitaxel armAdjuvant therapyAdverse eventsSusceptible patientsRisk factorsClinical trialsBreast cancerNeuropathyPaclitaxel treatmentClinical decisionPatientsPatient informationMaximum gradeHeritable componentMost individualsTreatment
2012
A Genome-Wide Association Study Identifies Novel Loci for Paclitaxel-Induced Sensory Peripheral Neuropathy in CALGB 40101
Baldwin RM, Owzar K, Zembutsu H, Chhibber A, Kubo M, Jiang C, Watson D, Eclov RJ, Mefford J, McLeod HL, Friedman PN, Hudis CA, Winer EP, Jorgenson EM, Witte JS, Shulman LN, Nakamura Y, Ratain MJ, Kroetz DL. A Genome-Wide Association Study Identifies Novel Loci for Paclitaxel-Induced Sensory Peripheral Neuropathy in CALGB 40101. Clinical Cancer Research 2012, 18: 5099-5109. PMID: 22843789, PMCID: PMC3445665, DOI: 10.1158/1078-0432.ccr-12-1590.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, PhytogenicBreast NeoplasmsFemaleGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansIncidenceMicrofilament ProteinsMiddle AgedPaclitaxelPeripheral Nervous System DiseasesPolymorphism, Single NucleotideReceptor, EphA5Sensory Receptor CellsConceptsSensory peripheral neuropathyWide association studyPeripheral neuropathyCALGB 40101Genome-wide association study identifies novel lociAssociation studiesPrimary breast cancerIdentification of patientsNovel genetic markersGenetic risk factorsAfrican American subjectsSingle nucleotide polymorphismsAdditional EuropeanNovel lociPaclitaxel armAdditional genesGenetic variationPaclitaxel therapyClinical managementRisk factorsBreast cancerDiscovery cohortPharmacogenetic analysisNeuropathyGenetic markers
2011
P1-17-02: A Phase 1/2 Study of SAR245408 (S08) in Combination with Trastuzumab (T) or Paclitaxel (P) and T in Patients with HER2+ Metastatic Breast Cancer (MBC) Who Progressed on a Previous T-Based Regimen.
Tolaney S, Burris H, Gartner E, Mayer I, Saura C, Maurer M, DeCillis A, Ruiz-Soto R, Lager J, Winer E, Krop I. P1-17-02: A Phase 1/2 Study of SAR245408 (S08) in Combination with Trastuzumab (T) or Paclitaxel (P) and T in Patients with HER2+ Metastatic Breast Cancer (MBC) Who Progressed on a Previous T-Based Regimen. Cancer Research 2011, 71: p1-17-02-p1-17-02. DOI: 10.1158/0008-5472.sabcs11-p1-17-02.Peer-Reviewed Original ResearchPhase 1/2 studyMetastatic breast cancerOverall response rateArm 1Arm 2Epigastric painMulticenter phase 1/2 studyPan-PI3K inhibitorECOG PS 0Preliminary PK dataDose-escalation designAge 55 yrPhase 2 portionDifferent dose levelsPhase 1PI3K pathwayDisease refractoryFemale ptsMost HER2Recurrent HER2MBC patientsMetastatic diseaseAdverse eventsPeripheral neuropathyPS 0