2023
Divarasib plus cetuximab in KRAS G12C-positive colorectal cancer: a phase 1b trial
Desai J, Alonso G, Kim S, Cervantes A, Karasic T, Medina L, Shacham-Shmueli E, Cosman R, Falcon A, Gort E, Guren T, Massarelli E, Miller W, Paz-Ares L, Prenen H, Amatu A, Cremolini C, Kim T, Moreno V, Ou S, Passardi A, Sacher A, Santoro A, Stec R, Ulahannan S, Arbour K, Lorusso P, Luo J, Patel M, Choi Y, Shi Z, Mandlekar S, Lin M, Royer-Joo S, Chang J, Jun T, Dharia N, Schutzman J, Han S. Divarasib plus cetuximab in KRAS G12C-positive colorectal cancer: a phase 1b trial. Nature Medicine 2023, 30: 271-278. PMID: 38052910, PMCID: PMC10803265, DOI: 10.1038/s41591-023-02696-8.Peer-Reviewed Original ResearchPhase 1b trialColorectal cancerSafety profileMedian progression-free survivalTreatment-related adverse eventsInhibitor-naive patientsKRAS G12C inhibitionAntitumor activityManageable safety profileObjective response rateProgression-free survivalPreliminary antitumor activityKRAS G12C mutationKRAS G12C inhibitorsEpidermal growth factor receptorVariant allele frequencyGrowth factor receptorAdverse eventsMedian durationTreatment withdrawalPoor prognosisDisease progressionArm CDose reductionG12C inhibitorsSingle-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation
Sacher A, LoRusso P, Patel M, Miller W, Garralda E, Forster M, Santoro A, Falcon A, Kim T, Paz-Ares L, Bowyer S, de Miguel M, Han S, Krebs M, Lee J, Cheng M, Arbour K, Massarelli E, Choi Y, Shi Z, Mandlekar S, Lin M, Royer-Joo S, Chang J, Dharia N, Schutzman J, Desai J. Single-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation. New England Journal Of Medicine 2023, 389: 710-721. PMID: 37611121, DOI: 10.1056/nejmoa2303810.Peer-Reviewed Original ResearchConceptsMedian progression-free survivalTreatment-related adverse eventsProgression-free survivalAdverse eventsSolid tumorsG12C mutationLow-grade adverse eventsGrade 3 eventsGrade 4 eventsTreatment-related deathsDiscontinuation of treatmentMetastatic solid tumorsPhase 1 studyDurable clinical responsesBiomarkers of responseKRAS G12C mutationAssessment of safetyVariant allele frequencyClinical responseColorectal cancerSerial assessmentDose reductionG12C inhibitorsPatientsTumor DNA
2011
Dose-escalating and pharmacological study of bortezomib in adult cancer patients with impaired renal function: a National Cancer Institute Organ Dysfunction Working Group Study
Leal T, Remick S, Takimoto C, Ramanathan R, Davies A, Egorin M, Hamilton A, LoRusso P, Shibata S, Lenz H, Mier J, Sarantopoulos J, Mani S, Wright J, Ivy S, Neuwirth R, von Moltke L, Venkatakrishnan K, Mulkerin D. Dose-escalating and pharmacological study of bortezomib in adult cancer patients with impaired renal function: a National Cancer Institute Organ Dysfunction Working Group Study. Cancer Chemotherapy And Pharmacology 2011, 68: 1439-1447. PMID: 21479634, PMCID: PMC3481841, DOI: 10.1007/s00280-011-1637-5.Peer-Reviewed Original ResearchConceptsSevere renal dysfunctionNormal renal functionRenal dysfunctionAdult cancer patientsRenal functionDialysis patientsDose escalationCancer patientsPatient populationNational Cancer Institute Organ Dysfunction Working Group StudyDose of bortezomibImpaired renal functionGeneral patient populationIntravenous bortezomibRenal impairmentCreatinine clearanceModerate dysfunctionMild dysfunctionSevere dysfunctionDose reductionPharmacologic dataPatientsDay 1DysfunctionBortezomib
2009
Cediranib, a VEGF receptor 1, 2, and 3 inhibitor, and pemetrexed in patients (pts) with recurrent non-small cell lung cancer (NSCLC)
Gadgeel S, Wozniak A, Edelman M, Valdivieso M, Heilbrun L, Venkatramanamoorthy R, Shields A, LoRusso P, Hackstock D, Ruckdeschel J. Cediranib, a VEGF receptor 1, 2, and 3 inhibitor, and pemetrexed in patients (pts) with recurrent non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2009, 27: e19007-e19007. DOI: 10.1200/jco.2009.27.15_suppl.e19007.Peer-Reviewed Original ResearchNon-small cell lung cancerRecurrent non-small cell lung cancerFLT-PET scansNSCLC ptsDose reductionPET scansMeasurable non-small cell lung cancerConfirmed response rateDisease control ratePhase II trialMedian age 60Cell lung cancerStandard uptake valueVEGF receptor 1Males 56Pemetrexed combinationsPrior regimensBrain metastasesGrade 3/4II trialVEGF therapyMajor hemorrhageOral inhibitorControl rateLung cancer