2024
A phase Ib/II study of pacritinib, an interleukin 1 receptor associated kinase 1 (IRAK1) inhibitor, in patients (pts) with solid tumors harboring the 1q21.3 copy number amplification (CNA).
Lim J, Aau M, Yeong J, Goh B, Yong W, Soo R, Wong A, Tan D, Chee C, Sundar R, Jeyasekharan A, Wong C, Chen P, Liu H, Yu Q, Tam W, Lee S. A phase Ib/II study of pacritinib, an interleukin 1 receptor associated kinase 1 (IRAK1) inhibitor, in patients (pts) with solid tumors harboring the 1q21.3 copy number amplification (CNA). Journal Of Clinical Oncology 2024, 42: 43-43. DOI: 10.1200/jco.2024.42.23_suppl.43.Peer-Reviewed Original ResearchProgression-free survivalT cell populationsCD8+ T cell populationsCopy number amplificationInterleukin-1 receptor-associated kinase 1Solid tumorsTumor microenvironmentCell populationsDose levelsCD4+ T cell populationRecommended phase II dosePlasma cell-free DNAPeripheral blood mononuclear cells analysisSystemic immune modulationPhase II doseRefractory solid tumorsPhase Ib/II clinical trialDose-expansion cohortDendritic cell populationsMyeloid cell populationsTumor biopsy samplesImmune cell populationsDecreased tumor growthModulated immune cell populationsPreclinical animal modelsCHAPTER-GIST-101: A phase I study of pimitespib combined with imatinib in patients with imatinib-refractory gastrointestinal stromal tumor.
Hirano H, Naito Y, Sundar R, Komatsu Y, Kurokawa Y, Li J, Ozaka M, Iwatsuki M, Chen J, Yen C, Zalcberg J, Roy A, Chen L, Nishida T, Doi T. CHAPTER-GIST-101: A phase I study of pimitespib combined with imatinib in patients with imatinib-refractory gastrointestinal stromal tumor. Journal Of Clinical Oncology 2024, 42: tps97-tps97. DOI: 10.1200/jco.2024.42.23_suppl.tps97.Peer-Reviewed Original ResearchDose-escalation partGastrointestinal stromal tumorsProgression-free survivalDays on/2 daysResistance to IMStromal tumorsImatinib-refractory gastrointestinal stromal tumorsInvestigator-assessed progression-free survivalAdvanced gastrointestinal stromal tumorsKinase-domain mutationsOvercome IM resistanceWeeks on/2 weeksDisease control rateDose-limiting toxicitySecond-line settingDuration of responseMaximum tolerated dosePhase I studyPhase 3 studyPhase 1 studySoft tissue sarcomasHsp90 inhibitorsInhibited tumor growthAnti-tumor activityOverall survivalMolecular 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 centreEfficacy and Safety of Trifluridine/Tipiracil-Containing Combinations in Colorectal Cancer and Other Advanced Solid Tumors: A Systematic Review
Shitara K, Falcone A, Fakih M, George B, Sundar R, Ranjan S, Van Cutsem E. Efficacy and Safety of Trifluridine/Tipiracil-Containing Combinations in Colorectal Cancer and Other Advanced Solid Tumors: A Systematic Review. The Oncologist 2024, 29: e601-e615. PMID: 38366864, PMCID: PMC11067808, DOI: 10.1093/oncolo/oyae007.Peer-Reviewed Original ResearchConceptsMetastatic colorectal cancerRefractory metastatic colorectal cancerAdverse eventsDiscontinuation rate due to adverse eventsColorectal cancerChemorefractory metastatic colorectal cancerSafety outcomesMedian overall survivalSafety of FTD/TPIProgression-free survivalAdvanced solid tumorsAssociated with improved outcomesEarly-phase studiesSystematic reviewOverall survivalFTD/TPIRetrospective studySolid tumorsBevacizumabClinical efficacyTargeted agentsTumor typesAntineoplastic agentsAdvanced cancerImprove outcomes
2023
Indirect 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 settingIndirect 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 comparisonsEffects of prior therapies on outcomes with trifluridine/tipiracil in patients with metastatic gastric/gastroesophageal junction cancer in a randomized phase III trial (TAGS)
Shitara K, George B, Taieb J, Sundar R, Fakih M, Makris L, Benhadji K, Ghidini M. Effects of prior therapies on outcomes with trifluridine/tipiracil in patients with metastatic gastric/gastroesophageal junction cancer in a randomized phase III trial (TAGS). Journal Of Cancer Research And Clinical Oncology 2023, 149: 9361-9374. PMID: 37213030, PMCID: PMC10374776, DOI: 10.1007/s00432-023-04813-z.Peer-Reviewed Original ResearchConceptsProgression-free survivalGastric/gastroesophageal junction cancerJunction cancerSurvival benefitSafety profileEastern Cooperative Oncology Group performance statusRandomized phase III trialAssociated with survival benefitMedian overall survivalPhase III trialsPost hoc exploratory analysisLater-lineTrifluridine/tipiracil treatmentHematologic toxicityPrior therapyMedian overallOverall survivalIII trialsPlacebo armPerformance statusResultsBaseline characteristicsMedian timeRamucirumabTherapy patternsClinical trialsEffectiveness of Immune Checkpoint Inhibitors in Patients With Advanced Esophageal Squamous Cell Carcinoma
Yap D, Leone A, Wong N, Zhao J, Tey J, Sundar R, Pietrantonio F. Effectiveness of Immune Checkpoint Inhibitors in Patients With Advanced Esophageal Squamous Cell Carcinoma. JAMA Oncology 2023, 9: 215-224. PMID: 36480211, PMCID: PMC9857522, DOI: 10.1001/jamaoncol.2022.5816.Peer-Reviewed Original ResearchConceptsAdvanced esophageal squamous cell carcinomaImmune checkpoint inhibitorsEsophageal squamous cell carcinomaSquamous cell carcinomaPD-L1 expressionKaplan-Meier curvesLow PD-L1 expressionFirst-line trialsProgression-free survivalDuration of responsePD-L1Overall survivalCell carcinomaRandomized clinical trialsPooled analysisClinical trialsCheckpoint inhibitorsTumor proportionEffect of immune checkpoint inhibitorsLow programmed death ligand 1Benefit of immune checkpoint inhibitorsHazard ratioSurvival dataFirst-line settingICI-based regimens
2022
Outcomes of a Phase II Study of Intraperitoneal Paclitaxel plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases
Chia D, Sundar R, Kim G, Ang J, Lum J, Nga M, Goh G, Seet J, Chee C, Tan H, Ho J, Ngoi N, Lee M, Muthu V, Chan G, Pang A, Ang Y, Choo J, Lim J, Teh J, Lwin A, Soon Y, Shabbir A, So J, Yong W. Outcomes of a Phase II Study of Intraperitoneal Paclitaxel plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases. Annals Of Surgical Oncology 2022, 29: 8597-8605. PMID: 36070113, DOI: 10.1245/s10434-022-11998-z.Peer-Reviewed Original ResearchConceptsGastric cancer peritoneal metastasisIP-PTXConversion surgeryIntraperitoneal paclitaxelMedian OSSystemic chemotherapyPeritoneal metastasisSC groupConversion to negative cytologyResultsThe median OSProgression-free survivalPhase II studyMethodsForty-four patientsIntravenous oxaliplatinMedian PFSOral capecitabineSystemic capecitabineExtraperitoneal metastasesNegative cytologyPeritoneal diseaseOverall survivalPerformance statusPrimary endpointSecondary endpointsIP cohortFirst-Line Systemic Therapies for Advanced Hepatocellular Carcinoma: A Systematic Review and Patient-Level Network Meta-Analysis
Fong K, Zhao J, Sultana R, Lee J, Lee S, Chan S, Yau T, Tai D, Sundar R, Too C. First-Line Systemic Therapies for Advanced Hepatocellular Carcinoma: A Systematic Review and Patient-Level Network Meta-Analysis. Liver Cancer 2022, 12: 7-18. PMID: 36872922, PMCID: PMC9982345, DOI: 10.1159/000526639.Peer-Reviewed Original ResearchAdvanced hepatocellular carcinomaProgression-free survivalFirst-line systemic therapyBarcelona Clinic Liver CancerNetwork meta-analysisOverall survivalStandard of careAlpha-fetoproteinHazard ratioOS benefitSystemic therapyFirst-lineHepatocellular carcinomaFirst-line combination therapyRandom-effects network meta-analysisCombination of atezolizumabInhibitor monoclonal antibodiesFirst-line therapyCochrane Controlled Register of TrialsMeta-analysisKaplan-Meier curvesIndividual patient-level dataCochrane Controlled RegisterRegister of TrialsExtrahepatic spreadSelective Internal Radiation Therapy with Yttrium-90 Resin Microspheres Followed by Gemcitabine plus Cisplatin for Unresectable Intrahepatic Cholangiocarcinoma: A Phase 2 Single-Arm Multicenter Clinical Trial
Chan S, Chotipanich C, Choo S, Kwang S, Mo F, Worakitsitisatorn A, Tai D, Sundar R, Ng D, Loke K, Li L, Ng K, Peng Y, Yu S. Selective Internal Radiation Therapy with Yttrium-90 Resin Microspheres Followed by Gemcitabine plus Cisplatin for Unresectable Intrahepatic Cholangiocarcinoma: A Phase 2 Single-Arm Multicenter Clinical Trial. Liver Cancer 2022, 11: 451-459. PMID: 36158588, PMCID: PMC9485918, DOI: 10.1159/000525489.Peer-Reviewed Original ResearchUnresectable intrahepatic cholangiocarcinomaProgression-free survivalSelective internal radiation therapyInternal radiation therapyIntrahepatic cholangiocarcinomaMedian OSRadiation therapyOverall survivalClinical trialsMedian cycle of chemotherapyMedian progression-free survivalResin yttrium-90 microspheresYttrium-90 resin microspheresTreatment-related adverse eventsIntent-to-treat populationResponse rateDisease control rateResponse Evaluation CriteriaYttrium-90 microspheresCycles of chemotherapyWithdrawal of consentMulticenter clinical trialInvestigator-initiated clinical trialStandard gemcitabineStandard chemotherapyPan-immune-inflammation value as a predictive biomarker for survival in advanced non-small cell lung cancer patients treated with immunotherapy.
Sooi K, Low J, Miow Q, Kumarakulasinghe N, Sundar R, Huang Y. Pan-immune-inflammation value as a predictive biomarker for survival in advanced non-small cell lung cancer patients treated with immunotherapy. Journal Of Clinical Oncology 2022, 40: e21095-e21095. DOI: 10.1200/jco.2022.40.16_suppl.e21095.Peer-Reviewed Original ResearchPan-immune-inflammation valueNon-small cell lung cancerProgression-free survivalAdvanced non-small cell lung cancerNon-small cell lung cancer patientsPD-L1Overall survivalPrognostic factorsPredictive biomarkersUnivariate analysisAdvanced non-small cell lung cancer patientsHigher PIVMedian progression-free survivalMultivariate analysisImmune checkpoint inhibitor therapyPredictor of survival outcomesCell lung cancer patientsPredictive valueImmune checkpoint inhibitorsPD-L1 statusAdvanced NSCLC patientsCheckpoint inhibitor therapyTreated with immunotherapyANCA-associated vasculitisECOG performance status
2021
Low Programmed Death-Ligand 1–Expressing Subgroup Outcomes of First-Line Immune Checkpoint Inhibitors in Gastric or Esophageal Adenocarcinoma
Zhao J, Yap D, Chan Y, Tan B, Teo C, Syn N, Smyth E, Soon Y, Sundar R. Low Programmed Death-Ligand 1–Expressing Subgroup Outcomes of First-Line Immune Checkpoint Inhibitors in Gastric or Esophageal Adenocarcinoma. Journal Of Clinical Oncology 2021, 40: 392-402. PMID: 34860570, DOI: 10.1200/jco.21.01862.Peer-Reviewed Original ResearchConceptsProgrammed death-ligand 1Combined positive scoreImmune checkpoint inhibitorsKEYNOTE-062First-line treatmentCheckMate-649Checkpoint inhibitorsEsophageal adenocarcinomaKaplan-MeierEstimate time-to-event outcomesFirst-line immune checkpoint inhibitorsPD-L1 combined positive scoreProgrammed death ligand 1 subgroupsPatients treated with pembrolizumabPD-L1-expressing tumorsRandomized phase III trialEfficacy of ICIsPD-L1 subgroupsProgression-free survivalDeath-ligand 1Phase III trialsUS Food and Drug AdministrationPrimary manuscriptsFood and Drug AdministrationCPS-1Epigenetic promoter alterations in GI tumour immune-editing and resistance to immune checkpoint inhibition
Sundar R, Huang K, Kumar V, Ramnarayanan K, Demircioglu D, Her Z, Ong X, Bin Adam Isa Z, Xing M, Tan A, Tai D, Choo S, Zhai W, Lim J, Thakur M, Molinero L, Cha E, Fasso M, Niger M, Pietrantonio F, Lee J, Jeyasekharan A, Qamra A, Patnala R, Fabritius A, De Simone M, Yeong J, Ng C, Rha S, Narita Y, Muro K, Guo Y, Skanderup A, So J, Yong W, Chen Q, Göke J, Tan P. Epigenetic promoter alterations in GI tumour immune-editing and resistance to immune checkpoint inhibition. Gut 2021, 71: 1277-1288. PMID: 34433583, PMCID: PMC9185816, DOI: 10.1136/gutjnl-2021-324420.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitionImmune microenvironmentHuman immune systemCheckpoint inhibitionActive human immune systemGastric cancerHuman T-cell infiltrationT cell cytolytic activityResistance to immune checkpoint inhibitionImmune systemProgression-free survivalImmunotherapy-treated patientsT cell infiltrationTumor immune microenvironmentT cell proportionsImmune-editingImmunotherapy resistanceFunctional in vivo studiesTumor kineticsHumanised miceAlternative promoter useTumor microenvironmentTherapeutic responseCytolytic activityImmune depletionLow‐dose pembrolizumab in the treatment of advanced non‐small cell lung cancer
Low J, Huang Y, Sooi K, Ang Y, Chan Z, Spencer K, Jeyasekharan A, Sundar R, Goh B, Soo R, Yong W. Low‐dose pembrolizumab in the treatment of advanced non‐small cell lung cancer. International Journal Of Cancer 2021, 149: 169-176. PMID: 33634869, PMCID: PMC9545741, DOI: 10.1002/ijc.33534.Peer-Reviewed Original ResearchConceptsAdvanced non-small cell lung cancerNon-small cell lung cancerProgression-free survivalCell lung cancerFood and Drug AdministrationOverall survivalTreatment of advanced non-small cell lung cancerLung cancerDose of pembrolizumabImmune-related toxicitiesEffectiveness of pembrolizumabWeight-based dosingRetrospective observational studyNational University HospitalDegrees of cost savingsCost-minimisation analysisFixed doseSurvival outcomesAsian patientsNo significant differencePembrolizumabOncogenic driversSingle agentLow dosesRandomised trialsOutcomes of a phase II study of intraperitoneal paclitaxel plus systemic capecitabine and oxaliplatin (XELOX) for gastric cancer with peritoneal metastases.
Chia D, Sundar R, Kim G, Ang J, Lum J, Nga M, Cheng Ean C, Tan H, Ho J, Ngoi N, Lee M, Muthu V, Chan G, Pang A, Ang Y, Choo J, Lim J, Shabbir A, Yong W, So J. Outcomes of a phase II study of intraperitoneal paclitaxel plus systemic capecitabine and oxaliplatin (XELOX) for gastric cancer with peritoneal metastases. Journal Of Clinical Oncology 2021, 39: 165-165. DOI: 10.1200/jco.2021.39.3_suppl.165.Peer-Reviewed Original ResearchIP paclitaxelSystemic chemotherapyPeritoneal metastasisConversion surgeryGastric cancerMedian OSSC groupProspective phase 2 trialIP groupProgression-free survivalPhase II studyBaseline performance statusWound-related complicationsStandard-of-careGCPM patientsIntraperitoneal paclitaxelIV oxaliplatinMedian PFSSystemic capecitabineExtraperitoneal metastasesNegative cytologyOverall survivalPerformance statusPrimary endpointSecondary endpoints
2020
The role of targeted therapy (TKI) in the treatment of advanced hepatocellular carcinoma (aHCC) in the era of immunotherapy: Real-world data using AI analytics from an academic medical center.
Wong R, Wu J, Leen A, Tey G, Asokumaran Y, Chan G, Siddappan C, Jeyasekharan A, Chee C, Yong W, Ngiam K, Sundar R. The role of targeted therapy (TKI) in the treatment of advanced hepatocellular carcinoma (aHCC) in the era of immunotherapy: Real-world data using AI analytics from an academic medical center. Journal Of Clinical Oncology 2020, 38: e16623-e16623. DOI: 10.1200/jco.2020.38.15_suppl.e16623.Peer-Reviewed Original ResearchAdvanced hepatocellular carcinomaEra of immunotherapySequence of therapySystemic therapyOverall survivalHCC patientsClinical outcomesManagement of advanced hepatocellular carcinomaTreated with first-line immunotherapyTreatment of advanced hepatocellular carcinomaFirst-line immunotherapyFirst-line TKIsSecond-line immunotherapySecond-line TKIsLoco-regional therapiesProgression-free survivalSecond-line therapySecond-line treatmentPillar of treatmentChild-Pugh scoreMinority of patientsSecond-lineFirst-lineMedian ageTargeted therapy
2019
Epigenomic promoter alterations predict for benefit from immune checkpoint inhibition in metastatic gastric cancer
Sundar R, Huang K, Qamra A, Kim K, Kim S, Kang W, Tan A, Lee J, Tan P. Epigenomic promoter alterations predict for benefit from immune checkpoint inhibition in metastatic gastric cancer. Annals Of Oncology 2019, 30: 424-430. PMID: 30624548, PMCID: PMC6442650, DOI: 10.1093/annonc/mdy550.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitionMetastatic gastric cancerT cell cytolytic activityResistance to immune checkpoint inhibitionCheckpoint inhibitionGastric cancerCytolytic activityImmune evasionMedian progression-free survivalPhase II clinical trial of patientsCancer treated with immunotherapyClinical trials of patientsMechanisms of immune evasionResponse rateTreated with pembrolizumabPhase II clinical trialProgression-free survivalFresh tumor biopsiesPost-treatment biopsiesCohort of patientsTrial of patientsEarly gastric cancerArchival tissue samplesClinical responseTumor biopsies