2020
Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis
Brastianos PK, Lee EQ, Cohen JV, Tolaney SM, Lin NU, Wang N, Chukwueke U, White MD, Nayyar N, Kim A, Alvarez-Breckenridge C, Krop I, Mahar MK, Bertalan MS, Shaw B, Mora JL, Goss N, Subramanian M, Nayak L, Dietrich J, Forst DA, Nahed BV, Batchelor TT, Shih HA, Gerstner ER, Moy B, Lawrence D, Giobbie-Hurder A, Carter SL, Oh K, Cahill DP, Sullivan RJ. Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis. Nature Medicine 2020, 26: 1280-1284. PMID: 32483359, DOI: 10.1038/s41591-020-0918-0.Peer-Reviewed Original ResearchConceptsPrimary endpointOpen-label phase 2 trialDose of pembrolizumabExtracranial disease progressionHigher adverse eventsPercentage of patientsPhase 2 studyPhase 2 trialSolid tumor malignanciesFraction of patientsDefinitive progressionUnacceptable toxicityAdverse eventsOverall survivalPatients 17Leptomeningeal carcinomatosisLeptomeningeal disseminationLung cancerDisease progressionOvarian cancerMetastatic cancerPembrolizumabBreast cancerGrade 3Patients
2015
SU2C Phase Ib Study of Paclitaxel and MK-2206 in Advanced Solid Tumors and Metastatic Breast Cancer
Gonzalez-Angulo AM, Krop I, Akcakanat A, Chen H, Liu S, Li Y, Culotta KS, Tarco E, Piha-Paul S, Moulder-Thompson S, Velez-Bravo V, Sahin AA, Doyle LA, Do KA, Winer EP, Mills GB, Kurzrock R, Meric-Bernstam F. SU2C Phase Ib Study of Paclitaxel and MK-2206 in Advanced Solid Tumors and Metastatic Breast Cancer. Journal Of The National Cancer Institute 2015, 107: dju493. PMID: 25688104, PMCID: PMC4342675, DOI: 10.1093/jnci/dju493.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsDrug Administration ScheduleDrug EruptionsFatigueFemaleHeterocyclic Compounds, 3-RingHumansHyperglycemiaMaleMaximum Tolerated DoseMiddle AgedNeoplasmsNeutropeniaPaclitaxelSeverity of Illness IndexTreatment OutcomeConceptsDose escalationDay 1Day 2Higher adverse eventsPhase Ib studyWeeks of therapyAdvanced solid tumorsCTCAE grade 3Metastatic breast cancerPrevious phase IPreliminary antitumor activityDose expansionStable diseaseObjective responseUnacceptable toxicityAdverse eventsMedian ageWeekly dosesClinical benefitPharmacodynamic markersSystemic exposureExcessive toxicityTumor responseGrade 3Median number