2021
RAF1 amplification drives a subset of bladder tumors and confers sensitivity to MAPK-directed therapeutics
Bekele RT, Samant AS, Nassar AH, So J, Garcia EP, Curran CR, Hwang JH, Mayhew DL, Nag A, Thorner AR, Börcsök J, Sztupinszki Z, Pan CX, Bellmunt J, Kwiatkowski DJ, Sonpavde GP, Van Allen EM, Mouw KW. RAF1 amplification drives a subset of bladder tumors and confers sensitivity to MAPK-directed therapeutics. Journal Of Clinical Investigation 2021, 131 PMID: 34554931, PMCID: PMC8592548, DOI: 10.1172/jci147849.Peer-Reviewed Original ResearchConceptsBladder tumorsUrothelial tumorsTherapeutic strategiesNovel therapeutic strategiesRational therapeutic strategiesPatient-derived modelsRaf/MEK/ERKClinical outcomesMEK/ERKTreatment optionsBladder cancerHeterogeneous diseaseMEK inhibitionTumorsUnique subsetFocal amplificationRAF inhibitorsCell linesRAF1Gene expression patternsActivationExpression patternsSignalingSubsetRaf1 activity
2020
Activity of cabozantinib after immune checkpoint blockade in metastatic clear-cell renal cell carcinoma
McGregor BA, Lalani AA, Xie W, Steinharter JA, Bakouny Z, Martini DJ, Fleischer JH, Abou-Alaiwi S, Nassar A, Nuzzo PV, Kaymakcalan MD, Braun DA, Wei XX, Harshman LC, Bilen MA, Choueiri TK. Activity of cabozantinib after immune checkpoint blockade in metastatic clear-cell renal cell carcinoma. European Journal Of Cancer 2020, 135: 203-210. PMID: 32599410, DOI: 10.1016/j.ejca.2020.05.009.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAngiogenesis InhibitorsAnilidesAntineoplastic Combined Chemotherapy ProtocolsBostonCarcinoma, Renal CellFemaleGeorgiaHumansImmune Checkpoint InhibitorsKidney NeoplasmsMaleMiddle AgedProtein Kinase InhibitorsPyridinesRetrospective StudiesTime FactorsTreatment OutcomeConceptsMetastatic clear cell renal cell carcinomaImmune checkpoint blockadeClear cell renal cell carcinomaActivity of cabozantinibRenal cell carcinomaOverall survivalTreatment failureCheckpoint blockadeCell carcinomaDose reductionAnti-PD-1/PD-L1International Metastatic RCC Database ConsortiumVascular endothelial growth factor inhibitorsSubsequent-line treatmentUse of cabozantinibIntermediate-risk groupMedian overall survivalMedian TTFHalf of patientsNew safety signalsPalmar-plantar erythrodysesthesiaPrimary progressive diseaseGrowth factor inhibitorsOverall response rateMost common reasons
2019
PD-L1 Expression and Clinical Outcomes to Cabozantinib, Everolimus, and Sunitinib in Patients with Metastatic Renal Cell Carcinoma: Analysis of the Randomized Clinical Trials METEOR and CABOSUN
Flaifel A, Xie W, Braun DA, Ficial M, Bakouny Z, Nassar AH, Jennings RB, Escudier B, George DJ, Motzer RJ, Morris MJ, Powles T, Wang E, Huang Y, Freeman GJ, Choueiri TK, Signoretti S. PD-L1 Expression and Clinical Outcomes to Cabozantinib, Everolimus, and Sunitinib in Patients with Metastatic Renal Cell Carcinoma: Analysis of the Randomized Clinical Trials METEOR and CABOSUN. Clinical Cancer Research 2019, 25: 6080-6088. PMID: 31371341, PMCID: PMC6801080, DOI: 10.1158/1078-0432.ccr-19-1135.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnilidesB7-H1 AntigenBiomarkers, TumorBiopsyCarcinoma, Renal CellChemotherapy, AdjuvantClinical Trials, Phase II as TopicClinical Trials, Phase III as TopicEverolimusFemaleHumansKaplan-Meier EstimateKidneyKidney NeoplasmsMulticenter Studies as TopicNephrectomyPrognosisProgression-Free SurvivalProtein Kinase InhibitorsPyridinesRandomized Controlled Trials as TopicSunitinibConceptsMetastatic renal cell carcinomaPD-L1 expressionProgression-free survivalOverall survivalRenal cell carcinomaPD-L1Clinical outcomesCell carcinomaPredictive biomarkersClinical trialsTumor cell PD-L1 expressionHigh PD-L1 expressionTC PD-L1 expressionImproved progression-free survivalTumor tissuePoor progression-free survivalIHC double stainingMET expression levelsImmune cell infiltratesPD-L1 statusWorse clinical outcomesPotential predictive biomarkersImmune cell densityIndependent central reviewCABOSUN trial