2019
PTEN loss is associated with resistance to cetuximab in patients with head and neck squamous cell carcinoma
Eze N, Lee JW, Yang DH, Zhu F, Neumeister V, Sandoval-Schaefer T, Mehra R, Ridge JA, Forastiere A, Chung CH, Burtness B. PTEN loss is associated with resistance to cetuximab in patients with head and neck squamous cell carcinoma. Oral Oncology 2019, 91: 69-78. PMID: 30926065, PMCID: PMC6855599, DOI: 10.1016/j.oraloncology.2019.02.026.Peer-Reviewed Original ResearchConceptsNeck squamous cell carcinomaEpidermal growth factor receptorSquamous cell carcinomaCell carcinomaCetuximab-based therapyTrial of cisplatinTrials (RCTs) of cetuximabPotential predictive biomarkersPTEN expressionLack of benefitPI3K mutationsPI3K p110αHigh PTEN expressionPI3K pathwayGrowth factor receptorHot spot mutationsStandard therapySuperior PFSMultivariable analysisPredictive biomarkersLoss of expressionSuch therapyCommon abnormalityCetuximabSide effectsPI3K oncogenic mutations mediate resistance to afatinib in HER2/neu overexpressing gynecological cancers
Bonazzoli E, Cocco E, Lopez S, Bellone S, Zammataro L, Bianchi A, Manzano A, Yadav G, Manara P, Perrone E, Haines K, Espinal M, Dugan K, Menderes G, Altwerger G, Han C, Zeybek B, Litkouhi B, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Santin AD. PI3K oncogenic mutations mediate resistance to afatinib in HER2/neu overexpressing gynecological cancers. Gynecologic Oncology 2019, 153: 158-164. PMID: 30630630, PMCID: PMC6430698, DOI: 10.1016/j.ygyno.2019.01.002.Peer-Reviewed Original ResearchMeSH KeywordsAdultAfatinibAgedAnimalsAntineoplastic AgentsCell Line, TumorClass I Phosphatidylinositol 3-KinasesClass Ia Phosphatidylinositol 3-KinaseDrug Resistance, NeoplasmFemaleGenital Neoplasms, FemaleHumansMiceMice, SCIDMiddle AgedMutationPhosphatidylinositol 3-KinasesProtein Kinase InhibitorsReceptor, ErbB-2TransfectionXenograft Model Antitumor AssaysConceptsHER2/neuAKT/mTOR pathwayPIK3CA mutationsMTOR pathwayActivity of afatinibEffect of afatinibPI3K/AKT/mTOR pathwayPotential mechanismsPIK3CA/AKT/mTOR pathwayRapid tumor growthGreater compensatory increasePI3K mutationsAmplification/mutationOncogenic PIK3CA mutationsAfatinib exposurePIK3CA H1047RGynecological cancerClinical trialsMTOR inhibitorsAfatinibTumor growthCompensatory increasePhosphorylated Akt proteinPIK3CA geneC-erb
2017
A phase II study of GDC-0032 (taselisib) for previously treated PI3K positive patients with stage IV squamous cell lung cancer (SqNSCLC): LUNG-MAP sub-study SWOG S1400B.
Wade J, Langer C, Redman M, Aggarwal C, Bradley J, Crawford J, Miao J, Griffin K, Herbst R, Kelly K, Gandara D, Papadimitrakopoulou V. A phase II study of GDC-0032 (taselisib) for previously treated PI3K positive patients with stage IV squamous cell lung cancer (SqNSCLC): LUNG-MAP sub-study SWOG S1400B. Journal Of Clinical Oncology 2017, 35: 9054-9054. DOI: 10.1200/jco.2017.35.15_suppl.9054.Peer-Reviewed Original ResearchPrimary endpointInterim analysisStage IV squamous cell lung cancerResponse rateSquamous cell lung cancerNational Clinical Trials NetworkSingle-arm phase II trialArm phase II trialGrade 3 AEsGrade 5 eventsPIK3CA-mutant tumorsPrimary analysis populationPhase II studyPhase II trialOverall survival dataCell lung cancerPlatinum-based therapyPrimary platinum-based therapyClinical Trials NetworkClinical trial informationPI3K mutationsPI3K pathwayEligible ptsMedian PFSStable disease
2014
PHASE II TRIAL OF THE PHOSPHATIDYINOSITOL-3 KINASE (PI3K) INHIBITOR BUPARLISIB (BKM120) IN RECURRENT GLIOBLASTOMA CONDUCTED BY THE IVY FOUNDATION EARLY PHASE CLINICAL TRIALS CONSORTIUM
Wen P, Wen P, Yung W, Mellinghoff I, Ramkissoon S, Alexander B, Rinne M, Colman H, Omuro A, DeAngelis L, Gilbert M, DeGroot J, Cloughesy T, Lee E, Nayak L, S. A, Batchelor T, Chang S, Prados M, Reardon D, Ligon K. PHASE II TRIAL OF THE PHOSPHATIDYINOSITOL-3 KINASE (PI3K) INHIBITOR BUPARLISIB (BKM120) IN RECURRENT GLIOBLASTOMA CONDUCTED BY THE IVY FOUNDATION EARLY PHASE CLINICAL TRIALS CONSORTIUM. Neuro-Oncology 2014, 16: iii47-iii47. PMCID: PMC4144634, DOI: 10.1093/neuonc/nou209.20.Peer-Reviewed Original ResearchPI3K pathwayCohort 2Cohort 1Pan-class I PI3K inhibitorEnzyme-inducing antiepileptic drugsAdequate bone marrowGrade 4 toxicityGrowth of U87K pathwayGrade 3 toxicityPhase II studyPhase II trialRecurrent GBM patientsAdditional eligibility criteriaALT/ASTSingle-agent efficacyPotential therapeutic targetPI3K mutationsReduction of pAKTPI3K inhibitorsEvaluable patientsMedian OSMedian PFSPrior bevacizumabRadiologic progression
2012
SU2C phase Ib study of pan-PI3K inhibitor BKM120 with letrozole in ER+/HER2- metastatic breast cancer (MBC).
Mayer I, Abramson V, Balko J, Isakoff S, Kuba M, Sanders M, Forero-Torres A, Yap J, Van Den Abbeele A, Li Y, Arteaga C, Winer E. SU2C phase Ib study of pan-PI3K inhibitor BKM120 with letrozole in ER+/HER2- metastatic breast cancer (MBC). Journal Of Clinical Oncology 2012, 30: 510-510. DOI: 10.1200/jco.2012.30.15_suppl.510.Peer-Reviewed Original ResearchMetastatic breast cancerPan-PI3K inhibitor BKM120FDG-PETArm API3K pathway alterationsPhase Ib studyPhase Ib trialPost-menopausal patientsPI3K pathway inhibitionPI3K mutationsPI3K inhibitorsIb trialStable diseaseVisceral metastasesUnacceptable toxicityMost patientsArm BMedian ageDisease progressionPharmacodynamic biomarkersBreast cancerTreatment responseTumor biopsiesAntiestrogen resistanceIb study
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply