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 setting
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
Molecular 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
2019
463P Evaluation of pharmacodynamic (PD) biomarkers in advanced cancer patients treated with oxidative phosphorylation (OXPHOS) inhibitor, OPC-317 (OPC)
Eu J, Yadav K, Lim Y, Hirpara J, Kong L, Ng Z, Lee V, Lee S, Tan D, Soo R, Chee C, Yong W, Sundar R, Lim J, Wang L, Ohi N, Tsunoda T, Pervaiz S, Goh B, Wong A. 463P Evaluation of pharmacodynamic (PD) biomarkers in advanced cancer patients treated with oxidative phosphorylation (OXPHOS) inhibitor, OPC-317 (OPC). Annals Of Oncology 2019, 30: v174. DOI: 10.1093/annonc/mdz244.025.Peer-Reviewed Original ResearchMitochondrial membrane potentialSerum metabolomeHER2+ breast cancerOncogene-addicted tumorsDose-finding phaseClinically tolerable dosesCancer stem cellsNon-significant riseG3/4 toxicitiesOxidative phosphorylation inhibitionSignificantly with treatmentGIST patientsTolerated doseTumor biopsiesImmunohistochemistry expressionCopy numberOxidative phosphorylationSerum lactateBreast cancerClinical developmentDrug resistanceMerck SeronoDose levelsDay 1Pathway inhibitorA phase Ib/II trial of lenvatinib (len) and letrozole (let) incorporating pharmacodynamics studies in postmenopausal women with hormone receptor positive (HR+) locally advanced/metastatic breast cancer (LABC/MBC).
Lim J, Wong A, Ow S, Eng L, Sundar R, Chan G, Yadav K, Heong V, Tan D, Soo R, Chee C, Yong W, Goh B, Lee S. A phase Ib/II trial of lenvatinib (len) and letrozole (let) incorporating pharmacodynamics studies in postmenopausal women with hormone receptor positive (HR+) locally advanced/metastatic breast cancer (LABC/MBC). Journal Of Clinical Oncology 2019, 37: 1045-1045. DOI: 10.1200/jco.2019.37.15_suppl.1045.Peer-Reviewed Original ResearchDose-limiting toxicityDisease control ratePalmar-plantar erythrodysesthesiaDose reductionBreast cancerDose levelsMechanisms of endocrine resistanceRecommended phase 2 dosePhase 2 doseAdvanced/metastatic breast cancerHR+ breast cancerPhase Ib trialContinuous daily dosingSerial tumor biopsiesAnti-tumor activityStandard of careDose expansionG3 toxicityPrior CTPostmenopausal womenTumor biopsiesEndocrine resistanceDaily doseEstrogen receptorPreclinical studies
2017
Genomic predictors of neoadjuvant chemotherapy (NACT) response in breast cancer (BC).
Wong A, Tan K, Sundar R, Ow S, Pang A, Yap H, Chan C, Hartman M, Iau P, Buhari S, Mogro M, Tan I, Wang L, Yang H, Goh B, Lee S. Genomic predictors of neoadjuvant chemotherapy (NACT) response in breast cancer (BC). Journal Of Clinical Oncology 2017, 35: e12122-e12122. DOI: 10.1200/jco.2017.35.15_suppl.e12122.Peer-Reviewed Original ResearchVariant allele frequencyNeoadjuvant chemotherapyPost-NACTPoor outcomeBC patientsBreast cancerPredictors of neoadjuvant chemotherapyEffect of neoadjuvant chemotherapyEmergent mutationsMean tumor sizePost-NACT tumorsSomatic single nucleotide variantsDiagnosed BC patientsSingle nucleotide variantsWhole-exome sequencingMatched normal DNABC relapseNOTCH2 mutationsTumor sizeClinical outcomesNucleotide variantsLesion reductionExome sequencingPatientsMutational landscapeProspective 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
2016
Low Levels of NDRG1 in Nerve Tissue Are Predictive of Severe Paclitaxel-Induced Neuropathy
Sundar R, Jeyasekharan A, Pang B, Soong R, Kumarakulasinghe N, Ow S, Ho J, Lim J, Tan D, Wilder-Smith E, Bandla A, Tan S, Asuncion B, Fazreen Z, Hoppe M, Putti T, Poh L, Goh B, Lee S. Low Levels of NDRG1 in Nerve Tissue Are Predictive of Severe Paclitaxel-Induced Neuropathy. PLOS ONE 2016, 11: e0164319. PMID: 27716814, PMCID: PMC5055363, DOI: 10.1371/journal.pone.0164319.Peer-Reviewed Original ResearchConceptsPaclitaxel-induced neuropathySevere neuropathyReceiver operating characteristicNerve tissueDose-limiting toxicityEarly breast cancerSensory peripheral neuropathyArea under the curveBreast cancer patientsIntensity of stainingWeekly paclitaxelSurgical resectionCharcot-Marie-ToothLimiting toxicitiesPredictive biomarkersNerve biopsyPeripheral neuropathyBreast cancerBiomarker strategiesCancer patientsNDRG1 expressionNeuropathyExpression scorePatientsPaclitaxel
2014
Phase II study of neoadjuvant weekly paclitaxel and carboplatin with lapatinib in HER2+ breast cancer.
Wong A, Tan S, Soh I, Tan C, Lim Y, Pang A, Ho J, Ow S, Sundar R, Pang M, Chan C, Buhari S, Hartman M, Iau P, Tang A, Wong N, Yap Y, Khoo B, Thiery J, Lee S. Phase II study of neoadjuvant weekly paclitaxel and carboplatin with lapatinib in HER2+ breast cancer. Journal Of Clinical Oncology 2014, 32: 619-619. DOI: 10.1200/jco.2014.32.15_suppl.619.Peer-Reviewed Original ResearchEffect of low-dose, short-course sunitinib (Su) on tumor vasculature and tumor blood flow for enhancement of chemotherapy efficacy in breast cancer.
Wong A, Sundar R, Ow S, Wang T, Ng T, Chan C, Hartman M, Iau P, Tan S, Zhang B, Thng C, Mogro M, Voon P, Buhari S, Soh I, Goh B, Lee S. Effect of low-dose, short-course sunitinib (Su) on tumor vasculature and tumor blood flow for enhancement of chemotherapy efficacy in breast cancer. Journal Of Clinical Oncology 2014, 32: 1060-1060. DOI: 10.1200/jco.2014.32.15_suppl.1060.Peer-Reviewed Original Research