2023
Outcomes With Combination Pembrolizumab and Axitinib in Second and Further Line Treatment of Metastatic Renal Cell Carcinoma
Dizman N, Austin M, Considine B, Jessel S, Schoenfeld D, Merl M, Hurwitz M, Sznol M, Kluger H. Outcomes With Combination Pembrolizumab and Axitinib in Second and Further Line Treatment of Metastatic Renal Cell Carcinoma. Clinical Genitourinary Cancer 2023, 21: 221-229. PMID: 36681606, DOI: 10.1016/j.clgc.2023.01.002.Peer-Reviewed Original ResearchConceptsMetastatic renal cell carcinomaPembrolizumab/axitinibObjective response rateProgression-free survivalImmune checkpoint inhibitorsMedian progression-free survivalAdverse eventsRenal cell carcinomaCell carcinomaClear cell metastatic renal cell carcinomaVascular endothelial growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsCombination immune checkpoint inhibitorsGrade 5 adverse eventsPrior immune checkpoint inhibitorsSuperior progression-free survivalReceptor tyrosine kinase inhibitorsYale-New Haven HospitalFurther-line treatmentNivolumab/ipilimumabRECIST 1.1 criteriaResponse-evaluable patientsDisease control rateSecond-line therapyFirst-line treatment
2021
Lifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma
Sarnaik AA, Hamid O, Khushalani NI, Lewis KD, Medina T, Kluger HM, Thomas SS, Domingo-Musibay E, Pavlick AC, Whitman ED, Martin-Algarra S, Corrie P, Curti BD, Oláh J, Lutzky J, Weber JS, Larkin JMG, Shi W, Takamura T, Jagasia M, Qin H, Wu X, Chartier C, Finckenstein F, Fardis M, Kirkwood JM, Chesney JA. Lifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma. Journal Of Clinical Oncology 2021, 39: 2656-2666. PMID: 33979178, PMCID: PMC8376325, DOI: 10.1200/jco.21.00612.Peer-Reviewed Original ResearchConceptsObjective response rateDisease control rateAdvanced melanomaPrimary refractoryControl rateMetastatic melanomaTreatment optionsInterleukin-2Investigator-assessed objective response rateHigh-dose interleukin-2Tumor-Infiltrating Lymphocyte TherapyImmune checkpoint inhibitorsPrimary end pointTumor-infiltrating lymphocytesEffective treatment optionLimited treatment optionsAdoptive cell therapyMajor unmet needLymphodepletion regimenPrior therapyCheckpoint inhibitorsAdverse eventsDurable responsesMedian durationPartial response
2019
Multiplex Quantitative Analysis of Tumor-Infiltrating Lymphocytes and Immunotherapy Outcome in Metastatic Melanoma
Wong PF, Wei W, Smithy JW, Acs B, Toki MI, Blenman K, Zelterman D, Kluger HM, Rimm DL. Multiplex Quantitative Analysis of Tumor-Infiltrating Lymphocytes and Immunotherapy Outcome in Metastatic Melanoma. Clinical Cancer Research 2019, 25: 2442-2449. PMID: 30617133, PMCID: PMC6467753, DOI: 10.1158/1078-0432.ccr-18-2652.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAntineoplastic Agents, ImmunologicalBiomarkersBiomarkers, TumorFemaleFluorescent Antibody TechniqueHumansImmunohistochemistryImmunotherapyKaplan-Meier EstimateLymphocytes, Tumor-InfiltratingMaleMelanomaMiddle AgedMolecular Targeted TherapyNeoplasm StagingROC CurveT-Lymphocyte SubsetsConceptsCell countTIL activationQuantitative immunofluorescenceLymphocytic infiltrationMelanoma patientsMetastatic melanomaAnti-PD-1 responseAnti-PD-1 therapyCell death 1 (PD-1) inhibitionAbsence of immunotherapyDeath-1 (PD-1) inhibitionDisease control rateProgression-free survivalCD8 cell countsTumor-Infiltrating LymphocytesNew predictive biomarkersWhole tissue sectionsRECIST 1.1Progressive diseaseDurable responsesObjective responsePartial responseImmunotherapy outcomesLymphocyte profilesMultivariable analysis
2018
Results of a Phase II Placebo-controlled Randomized Discontinuation Trial of Cabozantinib in Patients with Non–small-cell Lung Carcinoma
Hellerstedt BA, Vogelzang NJ, Kluger HM, Yasenchak CA, Aftab DT, Ramies DA, Gordon MS, Lara P. Results of a Phase II Placebo-controlled Randomized Discontinuation Trial of Cabozantinib in Patients with Non–small-cell Lung Carcinoma. Clinical Lung Cancer 2018, 20: 74-81.e1. PMID: 30528315, DOI: 10.1016/j.cllc.2018.10.006.Peer-Reviewed Original ResearchConceptsObjective response rateProgression-free survivalMedian progression-free survivalCell lung carcinomaWeek 12Adverse eventsDiscontinuation trialLung carcinomaTreatment-related grade 5 adverse eventsCommon grade 3/4 adverse eventsBioavailable tyrosine kinase inhibitorGrade 3/4 adverse eventsGrade 5 adverse eventsOverall disease control rateSolid Tumors version 1.0Epidermal growth factor receptor (EGFR) mutationsOpen-label leadPhase II PlaceboRandomized discontinuation trialDisease control ratePalmar-plantar erythrodysesthesiaResponse Evaluation CriteriaGrowth factor receptor 2Vascular endothelial growth factor receptor 2Endothelial growth factor receptor 2Safety and feasibility of immuno-cryotherapy.
Raja J, Ghodadra A, Gettinger S, Kluger H, Sznol M, Schalper K, "Kevin" Kim H. Safety and feasibility of immuno-cryotherapy. Journal Of Clinical Oncology 2018, 36: 34-34. DOI: 10.1200/jco.2018.36.5_suppl.34.Peer-Reviewed Original ResearchAdverse eventsImage-guided cryotherapyGrade 3Metastatic non-small cell lung cancerNon-small cell lung cancerImmune checkpoint inhibitor resistanceImmune checkpoint inhibitor therapyAdverse Events criteriaCheckpoint inhibitor resistanceCheckpoint inhibitor therapyCTLA-4 blockadeDisease control rateHigher adverse eventsImmune checkpoint inhibitionPrimary end pointImmune checkpoint therapyCell lung cancerTypes of malignanciesCases of diarrheaProgression of diseaseSystemic immunotherapyMetastatic NSCLCPeriprocedural periodSecondary endpointsSite hematoma
2012
Activity of cabozantinib (XL184) in metastatic NSCLC: Results from a phase II randomized discontinuation trial (RDT).
Hellerstedt B, Edelman G, Vogelzang N, Kluger H, Yasenchak C, Shen X, Ramies D, Gordon M, Lara P. Activity of cabozantinib (XL184) in metastatic NSCLC: Results from a phase II randomized discontinuation trial (RDT). Journal Of Clinical Oncology 2012, 30: 7514-7514. DOI: 10.1200/jco.2012.30.15_suppl.7514.Peer-Reviewed Original ResearchObjective tumor regressionMedian PFSTumor regressionWk 12Median age 67 yearsOverall disease control ratePost-baseline tumour assessmentPrior exposureActivity of cabozantinibDisease control rateGrade 3/4 AEsGrade 5 AEsMedian prior linesAge 67 yearsStudy days 1Dysregulation of METMET upregulationNSCLC ptsPrior EGFRPrior erlotinibRECIST responseTherapy 50Eligible patientsMeasurable diseaseMetastatic NSCLC