2024
Molecular profiling of metastatic breast cancer and target-based therapeutic matching in an Asian tertiary phase I oncology unit
Walsh R, Ong R, Cheo S, Low P, Jayagopal A, Lee M, Ngoi N, Ow S, Wong A, Lim S, Lim Y, Heong V, Sundar R, Soo R, Chee C, Yong W, Goh B, Lee S, Tan D, Lim J. Molecular profiling of metastatic breast cancer and target-based therapeutic matching in an Asian tertiary phase I oncology unit. Frontiers In Oncology 2024, 14: 1342346. PMID: 38812774, PMCID: PMC11133600, DOI: 10.3389/fonc.2024.1342346.Peer-Reviewed Original ResearchProlonged median progression-free survivalTumor mutational burdenObjective response rateMetastatic breast cancerHazard ratioNext-generation sequencingPhase I unitMedian OSMolecular profilingOverall survivalAssociated with prolonged median PFSBreast cancerMedian progression-free survivalTreatment outcomesTrials of targeted therapiesProgression-free survivalData cut-offBroad-panel next-generation sequencingTumor molecular profilingTreatment eventsFoundationOne CDxMBC patientsMutational burdenAssociated with improvementsTertiary centre
2023
Efficacy of Oral SERDs in the treatment of ER+, HER2 - metastatic breast cancer, a stratified analysis of the ESR1 wild type and mutant subgroups
Wong N, Yap D, Ong R, Zhao J, Chan Y, Tey J, Sundar R, Lim J, Dawood S. Efficacy of Oral SERDs in the treatment of ER+, HER2 - metastatic breast cancer, a stratified analysis of the ESR1 wild type and mutant subgroups. Annals Of Oncology 2023 PMID: 37871699, DOI: 10.1016/j.annonc.2023.10.122.Peer-Reviewed Original ResearchTreatment of physician's choiceIndividual patient dataOral SERDsMetastatic breast cancerPFS benefitKaplan MeierBreast cancerEstimate time-to-event outcomesHER2- metastatic breast cancerESR1 mutation statusIndividual patient data meta-analysisOverall populationAdvanced breast cancerMeta-analysisMutant subgroupESR1 mutationsEndocrine therapyMutation statusRandomised controlled trialsOverall cohortPooled analysisDrug classesPFSPhysician's choicePreferred Reporting ItemsIndirect Treatment Comparison of First-Line CDK4/6-Inhibitors in Post-Menopausal Patients with HR+/HER2− Metastatic Breast Cancer
Zhao J, Fong K, Chan Y, Tey J, Dawood S, Lee S, Finn R, Sundar R, Lim J. Indirect Treatment Comparison of First-Line CDK4/6-Inhibitors in Post-Menopausal Patients with HR+/HER2− Metastatic Breast Cancer. Cancers 2023, 15: 4558. PMID: 37760527, PMCID: PMC10527344, DOI: 10.3390/cancers15184558.Peer-Reviewed Original ResearchProgression-free survivalPost-menopausal patientsIndirect treatment comparisonCDK4/6 inhibitorsHR+/HER2- MBCOS differenceOverall survivalSurvival outcomesEndpoint of progression-free survivalFirst-line aromatase inhibitorsProgression-free survival differenceHR+/HER2- metastatic breast cancerPhase III randomized trialComparison of survival outcomesMetastatic breast cancerKaplan-Meier OSTreatment of patientsCox proportional-hazards modelProportional-hazards modelTreatment comparisonsIndirect pairwise comparisonsMONALEESA-2OS benefitAromatase inhibitorsBreast cancerPhase II study of trifluridine/tipiracil in metastatic breast cancers with or without prior exposure to fluoropyrimidines
Lim J, Ow S, Wong A, Lee M, Chan G, Low J, Sundar R, Choo J, Chong W, Ang Y, Tai B, Lee S. Phase II study of trifluridine/tipiracil in metastatic breast cancers with or without prior exposure to fluoropyrimidines. European Journal Of Cancer 2023, 193: 113311. PMID: 37717281, DOI: 10.1016/j.ejca.2023.113311.Peer-Reviewed Original ResearchMetastatic breast cancerObjective response rateProgression-free survivalPhase II studyCohort ABreast cancerDetermination of progression-free survivalSingle-arm phase II studyTreatment of metastatic breast cancerConsistent with known toxicitiesMedian progression-free survivalClinical benefit rateDose-confirmation phaseTreated with FTD/TPIDose modificationII studyCohort BBenefit rateFTD/TPISafety profileFluoropyrimidineGastric cancerPatientsResponse rateAntitumour activityPhase II study of trifluridine/tipiracil (FTD/TPI) in HER2-negative metastatic breast cancers with or without prior exposure to fluoropyrimidines.
Lim J, Ow S, Wong A, Lee M, Chan G, Low J, Sundar R, Choo J, Tai B, Lee S. Phase II study of trifluridine/tipiracil (FTD/TPI) in HER2-negative metastatic breast cancers with or without prior exposure to fluoropyrimidines. Journal Of Clinical Oncology 2023, 41: 1099-1099. DOI: 10.1200/jco.2023.41.16_suppl.1099.Peer-Reviewed Original ResearchObjective response rateMetastatic breast cancerProgression-free survivalPhase II studyLead-in phaseCohort ADose modificationBreast cancerDetermination of progression-free survivalSingle arm phase II studyHER2-negative metastatic breast cancerConsistent with known toxicitiesMedian progression-free survivalTreatment-related adverse eventsResponse rateDose-confirmation phaseEvents of neutropeniaTreated with FTD/TPIClinical benefit rateDose-limiting toxicityOral drug combinationsTreatment of patientsAnti-tumor activityThymidine phosphorylase inhibitorMetastatic settingEfficacy of oral selective estrogen receptor degraders (SERD)s in the treatment of estrogen receptor positive (ER+), HER2-negative metastatic breast cancer (MBC): A stratified analysis of the ESR1 wild type (wt) and mutant (mt) subgroups.
Zhao J, Wong Zhun Hong N, Yap D, Ong R, Sundar R, Lim J, Dawood S. Efficacy of oral selective estrogen receptor degraders (SERD)s in the treatment of estrogen receptor positive (ER+), HER2-negative metastatic breast cancer (MBC): A stratified analysis of the ESR1 wild type (wt) and mutant (mt) subgroups. Journal Of Clinical Oncology 2023, 41: 1096-1096. DOI: 10.1200/jco.2023.41.16_suppl.1096.Peer-Reviewed Original ResearchProgression free survival benefitTreatment of physician's choiceProgression free survivalMetastatic breast cancerEndocrine therapyESR1 mutationsOverall cohortEstrogen receptorKaplan MeierEstimate time-to-event outcomesHER2-negative metastatic breast cancerOral selective estrogen receptor degraderHER2- metastatic breast cancerSurvival dataTreatment of estrogen receptorSelective estrogen receptor degraderOverall populationCompare survival outcomesIPD meta-analysisMeta-analysisEstrogen receptor degraderOral SERDsPFS differenceCompared to ETFree survivalIndirect treatment comparison of first-line CDK4/6-inhibitors in post-menopausal patients with HR+/HER2- metastatic breast cancer.
Zhao J, Fong K, Chan Y, Tey J, Dawood S, Lee S, Finn R, Sundar R, Lim J. Indirect treatment comparison of first-line CDK4/6-inhibitors in post-menopausal patients with HR+/HER2- metastatic breast cancer. Journal Of Clinical Oncology 2023, 41: 1071-1071. DOI: 10.1200/jco.2023.41.16_suppl.1071.Peer-Reviewed Original ResearchProgression-free survivalPost-menopausal patientsIndirect treatment comparisonCDK4/6 inhibitorsPALOMA-2MONARCH 3OS differenceOverall survivalAromatase inhibitorsPatient-level time-to-event dataEndpoint of progression-free survivalFirst-line aromatase inhibitorsProgression-free survival differenceHR+/HER2- metastatic breast cancerHormone receptor positive (HR+)/human epidermal growth factor receptor 2Epidermal growth factor receptor 2Progression-free survival curvesPhase III randomized controlled trialsCDK4/6 inhibitor palbociclibMetastatic breast cancerPhase III studyKaplan-Meier OSCox proportional hazards modelsProportional hazards modelTreatment comparisons
2022
Phase Ib/II Dose Expansion Study of Lenvatinib Combined with Letrozole in Postmenopausal Women with Hormone Receptor-Positive Breast Cancer.
Lim J, Wong A, Ow S, Ngoi N, Chan G, Ang Y, Chong W, Lim S, Lim Y, Lee M, Choo J, Tan H, Yong W, Soo R, Tan D, Chee C, Sundar R, Yadav K, Jain S, Wang L, Tai B, Goh B, Lee S. Phase Ib/II Dose Expansion Study of Lenvatinib Combined with Letrozole in Postmenopausal Women with Hormone Receptor-Positive Breast Cancer. Clinical Cancer Research 2022, 28: 2248-2256. PMID: 35363275, DOI: 10.1158/1078-0432.ccr-21-4179.Peer-Reviewed Original ResearchConceptsBreast cancerDose expansionEstrogen receptorHormone receptor-positive breast cancerPhase II dose expansionRecommended phase II doseReceptor-positive breast cancerCDK4/6 inhibitor therapyDose-expansion studyPaired tumor biopsiesPhase Ib/II trialPhase II doseVascular normalization indexTreated with lenvatinibDose of lenvatinibER+/HER2- breast cancerMetastatic breast cancerPreliminary antitumor activityEstrogen-responsive genesLenvatinib combinationII doseMetastatic settingInhibitor therapyMultikinase inhibitorTumor biopsiesPhase Ib Dose-Finding Study of Varlitinib Combined with Weekly Paclitaxel With or Without Carboplatin ± Trastuzumab in Advanced Solid Tumors
Lee M, Wong A, Ow S, Sundar R, Tan D, Soo R, Chee C, Lim J, Yong W, Lim S, Goh B, Wang L, Lee S. Phase Ib Dose-Finding Study of Varlitinib Combined with Weekly Paclitaxel With or Without Carboplatin ± Trastuzumab in Advanced Solid Tumors. Targeted Oncology 2022, 17: 141-151. PMID: 35195837, PMCID: PMC8995271, DOI: 10.1007/s11523-022-00867-0.Peer-Reviewed Original ResearchConceptsHER2+ metastatic breast cancerDose-limiting toxicityMetastatic breast cancerBreast cancerSubcutaneous trastuzumabSolid tumorsConclusionsThe recommended phase II dosePharmacokinetic analysisRecommended phase II doseHER2+ breast cancerAdvanced solid tumorsPalliative systemic therapyMetastatic solid tumorsResultsThirty-seven patientsArea under the curveWeekly paclitaxelNeoadjuvant therapyStable diseaseFebrile neutropeniaPartial responseSystemic therapyMethodsEligible patientsEfficacy signalsElectrolyte disturbancesBiliary tract
2020
Clinical efficacy and molecular effects of lenvatinib (Len) and letrozole (Let) in hormone receptor-positive (HR+) metastatic breast cancer (MBC).
Lim J, Wong A, Ow S, Ngoi N, Ang Y, Chan G, Eng L, Chong W, Choo J, Lee M, Tan H, Jan Y, Tan K, Sundar R, Tan D, Soo R, Chee C, Yong W, Goh B, Lee S. Clinical efficacy and molecular effects of lenvatinib (Len) and letrozole (Let) in hormone receptor-positive (HR+) metastatic breast cancer (MBC). Journal Of Clinical Oncology 2020, 38: 1019-1019. DOI: 10.1200/jco.2020.38.15_suppl.1019.Peer-Reviewed Original ResearchDisease control rateObjective response rateMetastatic breast cancerEffect of lenvatinibDose escalationEndocrine therapyEfficacy dataRecommended phase 2 doseAll-grade toxicitiesPhase 2 doseDose-escalation phaseHormone receptor-positiveDuration of responsePhase Ib/II studyTumor molecular profilingSerial tumor biopsiesAnti-tumor activityMolecular effectsMedian DoRPrior CTPALB2 mutationsProgression-freeExpansion cohortMBC patientsReceptor-positiveMolecular profiling of metastatic breast cancer (MBC) and target-based therapeutic matching in an Asian tertiary phase I oncology unit.
Walsh R, Ngoi N, Ong R, Ow S, Wong A, Eng L, Lim Y, Heong V, Sundar R, Soo R, Yong W, Chee C, Goh B, Lee S, Tan D, Lim J. Molecular profiling of metastatic breast cancer (MBC) and target-based therapeutic matching in an Asian tertiary phase I oncology unit. Journal Of Clinical Oncology 2020, 38: 3561-3561. DOI: 10.1200/jco.2020.38.15_suppl.3561.Peer-Reviewed Original ResearchMedian progression free survivalTriple negative breast cancerPhase I unitMolecular profilingEndocrine therapyNext generation sequencingBreast cancerClinical benefit rateProgression free survivalMetastatic breast cancerPhase I studyTumor molecular profilingNegative breast cancerNext generation sequencing findingsPIK3CA E542KPan-FGFR inhibitorMatched PTPIK3CA H1047RFree survivalMBC patientsMetastatic sitesI unitsFGFR pathwayTertiary centreTumor subtypes
2017
Prospective study of UDP-glucuronosyltransferase (UGT) 2B17 genotype and exemestane (Exe) pharmacokinetics (PK) and pharmacodynamics (PD) in Asian, hormone receptor (HR) positive, metastatic breast cancer (MBC) patients.
Walsh R, Lee S, Seng K, Wang L, Ho G, Ow S, Kumarakulasinghe N, Sundar R, Lee X, Yap H, Jeyasekharan A, Pang A, Ho J, Tan C, Lim Y, Malik R, Wan Ishak W, Goh B, Tai B, Wong A. Prospective study of UDP-glucuronosyltransferase (UGT) 2B17 genotype and exemestane (Exe) pharmacokinetics (PK) and pharmacodynamics (PD) in Asian, hormone receptor (HR) positive, metastatic breast cancer (MBC) patients. Journal Of Clinical Oncology 2017, 35: 1056-1056. DOI: 10.1200/jco.2017.35.15_suppl.1056.Peer-Reviewed Original ResearchClinical benefit rateMetastatic breast cancerHormone receptorsMetastatic breast cancer patientsUDP-glucuronosyltransferaseClinical treatment efficacyGlucuronidation in vitroUGT2B17 genotypeBenefit rateClinical benefitProspective studyBreast cancerActive metabolitePK dataPD biomarkersTreatment efficacyPatientsPharmacodynamicsPD effectsResponse rateUGT2B17C maxActivity indexPharmacokineticsSignificant PD