2024
First-line Systemic Therapy Following Adjuvant Immunotherapy in Renal Cell Carcinoma: An International Multicenter Study
El Zarif T, Semaan K, Xie W, Eid M, Zarba M, Issa W, Zhang T, Nguyen C, Alva A, Fahey C, Beckermann K, Karam J, Campbell M, Procopio G, Stellato M, Buti S, Zemankova A, Melichar B, Massari F, Mollica V, Venugopal B, Ebrahimi H, de Velasco G, Gurney H, De Giorgi U, Parikh O, Winquist E, Master V, Garcia A, Cutuli H, Ferguson T, Gross-Goupil M, Baca S, Pal S, Braun D, McKay R, Heng D, Choueiri T. First-line Systemic Therapy Following Adjuvant Immunotherapy in Renal Cell Carcinoma: An International Multicenter Study. European Urology 2024 PMID: 39147674, DOI: 10.1016/j.eururo.2024.07.016.Peer-Reviewed Original ResearchRenal cell carcinomaProgression-free survivalInternational Metastatic RCC Database ConsortiumRecurrent renal cell carcinomaTreatment-related adverse eventsSystemic therapyAdjuvant pembrolizumabOverall survivalCell carcinomaClinical outcomesIO therapyAdjuvant immunotherapyAdverse eventsVascular endothelial growth factor-targeted therapyDetect occult metastatic diseaseOutcomes of first-lineFirst-line systemic therapyFavorable-risk diseaseIO-based regimensOccult metastatic diseaseMedian follow-upKaplan-Meier methodShort follow-up periodFollow-up periodInternational multicenter study22 Association of a germline single nucleotide polymorphism (SNP) in the interleukin-7 (IL7) gene with immune-related adverse events (irAEs)
Saad E, Mehrabad E, Labaki C, Saliby R, Semaan K, Eid M, Machaalani M, Chehade R, Nawfal R, Sun M, Sharon E, Shah P, Vemula S, Gupta S, Braun D, Van Allen E, Gusev A, Choueiri T. 22 Association of a germline single nucleotide polymorphism (SNP) in the interleukin-7 (IL7) gene with immune-related adverse events (irAEs). The Oncologist 2024, 29: s1-s2. PMCID: PMC11301885, DOI: 10.1093/oncolo/oyae181.003.Peer-Reviewed Original ResearchImmune-related adverse eventsMetastatic non-small cell lung cancerMetastatic renal cell carcinomaImmune checkpoint inhibitorsProgression-free survivalWhole-exome sequencingRecurrent grade 2Overall survivalGrade 2Interleukin-7Single nucleotide polymorphismsNivolumab armPembrolizumab armSomatic alterationsAdverse eventsTreatment armsPrediction of immune-related adverse eventsCumulative rates of adverse eventsTumor whole-exome sequencingRates of grade 2Non-small cell lung cancerGermline single nucleotide polymorphismsClinical trials of patientsAssociated with significantly higher ratesPD-1 inhibitors45 INTerpath-004: A phase 2, randomized, double-blind study of pembrolizumab with V940 (mRNA-4157) or placebo in the adjuvant treatment of renal cell carcinoma
Choueiri T, Powles T, Braun D, Fong L, George D, Haas N, McDermott D, Shuch B, Gurney H, Meehan R, Posadas T, Wu S, Elfiky A, Motzer R. 45 INTerpath-004: A phase 2, randomized, double-blind study of pembrolizumab with V940 (mRNA-4157) or placebo in the adjuvant treatment of renal cell carcinoma. The Oncologist 2024, 29: s15-s15. PMCID: PMC11301864, DOI: 10.1093/oncolo/oyae181.022.Peer-Reviewed Original ResearchRenal cell carcinomaWeeks prior to randomizationAdverse eventsAdjuvant treatmentCell carcinomaResection of metastatic lesionsAdjuvant treatment of patientsPD-1 inhibitor pembrolizumabIncreased risk of recurrenceAdjuvant treatment of renal cell carcinomaTreatment of renal cell carcinomaActivity of pembrolizumabStage III/IV melanomaStudy of pembrolizumabDisease-free survivalMetastasis-free survivalPhase 2 trialRisk of recurrenceDouble-blind studyTreatment of patientsNovel combination strategiesDose of treatmentAdjuvant pembrolizumabAdjuvant settingInhibitor pembrolizumab
2022
Germline variants associated with toxicity to immune checkpoint blockade
Groha S, Alaiwi S, Xu W, Naranbhai V, Nassar A, Bakouny Z, El Zarif T, Saliby R, Wan G, Rajeh A, Adib E, Nuzzo P, Schmidt A, Labaki C, Ricciuti B, Alessi J, Braun D, Shukla S, Keenan T, Van Allen E, Awad M, Manos M, Rahma O, Zubiri L, Villani A, Fairfax B, Hammer C, Khan Z, Reynolds K, Semenov Y, Schrag D, Kehl K, Freedman M, Choueiri T, Gusev A. Germline variants associated with toxicity to immune checkpoint blockade. Nature Medicine 2022, 28: 2584-2591. PMID: 36526723, PMCID: PMC10958775, DOI: 10.1038/s41591-022-02094-6.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsImmune checkpoint inhibitorsGrade immune-related adverse eventsGermline variantsICI initiationCheckpoint inhibitorsAdverse eventsCheckpoint blockadeImproved survivalDiscovery cohortLymphocyte homeostasisSignificant associationCancer typesIL7Remarkable responsePatientsCritical regulatorGenome-wide significant associationAssociationWide association studyIndependent studiesAssociation studiesBlockadeCohortVariants