2021
Clinical Outcomes and Toxic Effects of Single-Agent Immune Checkpoint Inhibitors Among Patients Aged 80 Years or Older With Cancer
Nebhan CA, Cortellini A, Ma W, Ganta T, Song H, Ye F, Irlmeier R, Debnath N, Saeed A, Radford M, Alahmadi A, Diamond A, Hoimes C, Ramaiya N, Presley CJ, Owen DH, Alaiwi S, Nassar A, Ricciuti B, Lamberti G, Bersanelli M, Casartelli C, Buti S, Marchetti P, Giusti R, Filetti M, Vanella V, Mallardo D, Macherla S, Sussman TA, Botticelli A, Galetta D, Catino A, Pizzutilo P, Genova C, Dal Bello MG, Kalofonou F, Daniels E, Ascierto PA, Pinato DJ, Choueiri TK, Johnson DB, Marron TU, Wang Y, Naqash AR. Clinical Outcomes and Toxic Effects of Single-Agent Immune Checkpoint Inhibitors Among Patients Aged 80 Years or Older With Cancer. JAMA Oncology 2021, 7: 1856-1861. PMID: 34734989, PMCID: PMC8569601, DOI: 10.1001/jamaoncol.2021.4960.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsImmune checkpoint inhibitorsSingle-agent immune checkpoint inhibitorsGeriatric patientsClinical outcomesICI initiationCheckpoint inhibitorsAdverse eventsAnti-programmed cell death-1 therapySafety of ICIsNon-small cell lung cancerPatients Aged 80 YearsInternational retrospective studyCommon Terminology CriteriaInternational cohort studyObjective response rateDiscontinuation of treatmentCell lung cancerCancer clinical trialsGU tumorsICI discontinuationIrAE onsetMedian PFSTerminology CriteriaCohort studyRAF1 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 activityIntegrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma
Bakouny Z, Braun DA, Shukla SA, Pan W, Gao X, Hou Y, Flaifel A, Tang S, Bosma-Moody A, He MX, Vokes N, Nyman J, Xie W, Nassar AH, Abou Alaiwi S, Flippot R, Bouchard G, Steinharter JA, Nuzzo PV, Ficial M, Sant’Angelo M, Forman J, Berchuck JE, Dudani S, Bi K, Park J, Camp S, Sticco-Ivins M, Hirsch L, Baca SC, Wind-Rotolo M, Ross-Macdonald P, Sun M, Lee GM, Chang SL, Wei XX, McGregor BA, Harshman LC, Genovese G, Ellis L, Pomerantz M, Hirsch MS, Freedman ML, Atkins MB, Wu CJ, Ho TH, Linehan WM, McDermott DF, Heng DYC, Viswanathan SR, Signoretti S, Van Allen EM, Choueiri TK. Integrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma. Nature Communications 2021, 12: 808. PMID: 33547292, PMCID: PMC7865061, DOI: 10.1038/s41467-021-21068-9.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalB7-H1 AntigenCarcinoma, Renal CellCTLA-4 AntigenCyclin-Dependent Kinase Inhibitor p16Gene Expression ProfilingGene Expression Regulation, NeoplasticHigh-Throughput Nucleotide SequencingHumansImmune Checkpoint InhibitorsImmune Checkpoint ProteinsKidney NeoplasmsMutationProgrammed Cell Death 1 ReceptorProto-Oncogene Proteins c-mycRetrospective StudiesRhabdoid TumorSignal TransductionSurvival AnalysisTranscription, GeneticTumor Suppressor ProteinsUbiquitin ThiolesteraseConceptsRhabdoid renal cell carcinomaImmune checkpoint inhibitorsRenal cell carcinomaCell carcinomaImmune-inflamed phenotypeIntegrative molecular characterizationPD-L1 expressionReal-world cohortMultiple clinical trialsMYC transcriptional programsMolecular featuresCheckpoint inhibitorsClinical outcomesImmune activationImmunologic characteristicsAggressive tumorsImmune infiltrationClinical trialsClinical characterizationRCC tumorsBAP1 mutationsDistinctive molecular featuresTumorsCDKN2A deletionMolecular drivers
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