Clinical Efficacy and Molecular Response Correlates of the WEE1 Inhibitor Adavosertib Combined with Cisplatin in Patients with Metastatic Triple-Negative Breast Cancer
Keenan TE, Li T, Vallius T, Guerriero JL, Tayob N, Kochupurakkal B, Davis J, Pastorello R, Tahara RK, Anderson L, Conway J, He MX, Shannon E, Godin RE, Sorger PK, D'Andrea A, Overmoyer B, Winer EP, Mittendorf EA, Van Allen EM, Shapiro GI, Tolaney SM. Clinical Efficacy and Molecular Response Correlates of the WEE1 Inhibitor Adavosertib Combined with Cisplatin in Patients with Metastatic Triple-Negative Breast Cancer. Clinical Cancer Research 2021, 27: 983-991. PMID: 33257427, PMCID: PMC7887044, DOI: 10.1158/1078-0432.ccr-20-3089.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerObjective response rateTriple-negative breast cancerWEE1 inhibitor adavosertibPrior linesClinical benefitBreast cancerMedian progression-free survivalTreatment-related grade 3One-sided type I errorImmune-infiltrated tumorsPhase II studyProgression-free survivalT cell infiltrationImmune gene expressionPrior chemotherapyStable diseaseProtocol therapyII studyPartial responseAdverse eventsMedian ageClinical efficacyGrade 3Tumor biopsiesPhase I study of JAK1/2 inhibitor ruxolitinib with weekly paclitaxel for the treatment of HER2-negative metastatic breast cancer
Lynce F, Williams JT, Regan MM, Bunnell CA, Freedman RA, Tolaney SM, Chen WY, Mayer EL, Partridge AH, Winer EP, Overmoyer B. Phase I study of JAK1/2 inhibitor ruxolitinib with weekly paclitaxel for the treatment of HER2-negative metastatic breast cancer. Cancer Chemotherapy And Pharmacology 2021, 87: 673-679. PMID: 33585999, DOI: 10.1007/s00280-021-04245-x.Peer-Reviewed Original ResearchConceptsHER2-negative metastatic breast cancerMetastatic breast cancerBreast cancerWeekly paclitaxelAdvanced diseaseHormone receptor-positive diseaseTriple-negative breast cancerGrade 4/5 toxicitiesMost frequent toxicitiesPhase 2 doseWeekly paclitaxel 80Receptor-positive diseaseDose-escalation designJAK1/2 inhibitor ruxolitinibCombination of ruxolitinibBreast cancer cellsOral ruxolitinibPaclitaxel 80PurposePreclinical studiesChemotherapy regimensFrequent toxicitiesProtocol therapyMethodsEligible patientsThirteen patientsVisceral disease