2022
Phase 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 rate
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
2015
A phase 1b trial of blood-brain barrier (BBB)-penetrant tyrosine kinase inhibitor (TKI) tesevatinib in combination with trastuzumab for patients with HER2+ metastatic breast cancer (MBC).
Jhaveri K, Hamilton E, Miller K, Roche M, Berger M, Winer E, Lin N. A phase 1b trial of blood-brain barrier (BBB)-penetrant tyrosine kinase inhibitor (TKI) tesevatinib in combination with trastuzumab for patients with HER2+ metastatic breast cancer (MBC). Journal Of Clinical Oncology 2015, 33: 608-608. DOI: 10.1200/jco.2015.33.15_suppl.608.Peer-Reviewed Original Research