2022
Mutational Signature 3 Detected from Clinical Panel Sequencing is Associated with Responses to Olaparib in Breast and Ovarian Cancers
Batalini F, Gulhan DC, Mao V, Tran A, Polak M, Xiong N, Tayob N, Tung NM, Winer EP, Mayer EL, Knappskog S, Lønning PE, Matulonis UA, Konstantinopoulos PA, Solit DB, Won H, Eikesdal HP, Park PJ, Wulf GM. Mutational Signature 3 Detected from Clinical Panel Sequencing is Associated with Responses to Olaparib in Breast and Ovarian Cancers. Clinical Cancer Research 2022, 28: of1-of10. PMID: 36048535, PMCID: PMC9623231, DOI: 10.1158/1078-0432.ccr-22-0749.Peer-Reviewed Original ResearchConceptsHomologous recombination deficiencyTriple-negative breast cancerMutational signature 3Ovarian cancerImproved progression-free survivalPARP inhibitorsPanel sequencingHigh-grade serous ovarian cancerPI3K inhibitor buparlisibPhase Ib trialProgression-free survivalIdentification of patientsRoutine clinical careSignature 3Serous ovarian cancerPARP inhibitor olaparibSame patient sampleIb trialObjective responseTNBC patientsBreast cancerBRCA1/2 mutationsClinical careInstability scoreGenomic instability score
2018
Homologous recombination deficiency and host anti-tumor immunity in triple-negative breast cancer
Telli ML, Stover DG, Loi S, Aparicio S, Carey LA, Domchek SM, Newman L, Sledge GW, Winer EP. Homologous recombination deficiency and host anti-tumor immunity in triple-negative breast cancer. Breast Cancer Research And Treatment 2018, 171: 21-31. PMID: 29736741, DOI: 10.1007/s10549-018-4807-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsB7-H1 AntigenBiomarkers, TumorDisease SusceptibilityDNA DamageDNA RepairFemaleGene Expression Regulation, NeoplasticGenes, BRCA1Genes, BRCA2Germ-Line MutationHomologous RecombinationHumansImmunityImmunomodulationMolecular Targeted TherapyProgrammed Cell Death 1 ReceptorTriple Negative Breast NeoplasmsConceptsHost anti-tumor immunityAnti-tumor immunityHomologous recombination deficiencyBreast cancerPurposeTriple-negative breast cancerAnti-tumor immune cellsRecombination deficiencyTriple-negative breast cancerCare systemic therapyImmune-directed therapiesImmune cell subsetsHomologous recombination DNA repair deficiencyBRCA2 mutation carriersBiomarker-driven approachBreast cancer subtypesPARP inhibitor olaparibHR-deficient tumorsDNA repair capacityMetastatic diseaseSystemic therapyImmune infiltratesImproved prognosisCell subsetsImmune cellsWorse outcomes
2014
A randomized phase 2 trial comparing efficacy of the combination of the PARP inhibitor olaparib and the antiangiogenic cediranib against olaparib alone in recurrent platinum-sensitive ovarian cancer.
Liu J, Barry W, Birrer M, Lee J, Buckanovich R, Fleming G, Rimel B, Buss M, Nattam S, Hurteau J, Luo W, Quy P, Obermayer E, Whalen C, Lee H, Winer E, Kohn E, Ivy S, Matulonis U. A randomized phase 2 trial comparing efficacy of the combination of the PARP inhibitor olaparib and the antiangiogenic cediranib against olaparib alone in recurrent platinum-sensitive ovarian cancer. Journal Of Clinical Oncology 2014, 32: lba5500-lba5500. DOI: 10.1200/jco.2014.32.18_suppl.lba5500.Peer-Reviewed Original ResearchProgression-free survivalPartial responseComplete responseHazard ratioOvarian cancerRecurrent platinum-sensitive ovarian cancerMedian progression-free survivalPrior anti-angiogenic therapyPARP inhibitorsPlatinum-sensitive ovarian cancerRandomized phase 2 trialOpen-label studyRecurrent ovarian cancerPhase 2 trialPhase 1 studyExploratory subgroup analysisAnti-angiogenic therapyCombination of cediranibPARP inhibitor olaparibMeasurable diseaseRECIST 1.1Radiographic progressionPFS eventsPS 0Oral combinationA randomized phase 2 trial comparing efficacy of the combination of the PARP inhibitor olaparib and the antiangiogenic cediranib against olaparib alone in recurrent platinum-sensitive ovarian cancer.
Liu J, Barry W, Birrer M, Lee J, Buckanovich R, Fleming G, Rimel B, Buss M, Nattam S, Hurteau J, Luo W, Quy P, Obermayer E, Whalen C, Lee H, Winer E, Kohn E, Ivy S, Matulonis U. A randomized phase 2 trial comparing efficacy of the combination of the PARP inhibitor olaparib and the antiangiogenic cediranib against olaparib alone in recurrent platinum-sensitive ovarian cancer. Journal Of Clinical Oncology 2014, 32: lba5500-lba5500. DOI: 10.1200/jco.2014.32.15_suppl.lba5500.Peer-Reviewed Original Research
2011
A phase I trial of the PARP inhibitor olaparib (AZD2281) in combination with the antiangiogenic cediranib (AZD2171) in recurrent ovarian or triple-negative breast cancer.
Liu J, Fleming G, Tolaney S, Birrer M, Penson R, Berlin S, Whalen C, Tyburski K, Matijevich K, Kasparian E, Roche M, Lee H, Winer E, Ivy S, Matulonis U. A phase I trial of the PARP inhibitor olaparib (AZD2281) in combination with the antiangiogenic cediranib (AZD2171) in recurrent ovarian or triple-negative breast cancer. Journal Of Clinical Oncology 2011, 29: 5028-5028. DOI: 10.1200/jco.2011.29.15_suppl.5028.Peer-Reviewed Original Research