2022
Phase II Study of Taselisib in PIK3CA-Mutated Solid Tumors Other Than Breast and Squamous Lung Cancer: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol I
Krop IE, Jegede OA, Grilley-Olson JE, Lauring JD, Mitchell EP, Zwiebel JA, Gray RJ, Wang V, McShane LM, Rubinstein LV, Patton D, Williams PM, Hamilton SR, Kono SA, Ford JM, Garcia AA, Sui XD, Siegel RD, Slomovitz BM, Conley BA, Arteaga CL, Harris LN, O'Dwyer PJ, Chen AP, Flaherty KT. Phase II Study of Taselisib in PIK3CA-Mutated Solid Tumors Other Than Breast and Squamous Lung Cancer: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol I. JCO Precision Oncology 2022, 6: e2100424. PMID: 35138919, PMCID: PMC8865530, DOI: 10.1200/po.21.00424.Peer-Reviewed Original ResearchConceptsProgression-free survivalOverall survivalSix-month progression-free survivalSolid tumorsMedian progression-free survivalSix-month overall survivalEnd pointSquamous cell lung carcinomaNational Cancer Institute-Molecular AnalysisMedian overall survivalObjective response ratePhase II studyPrimary end pointSecondary end pointsCell lung carcinomaSquamous lung cancerMutant breast cancerCommon toxicitiesEligible patientsProtocol therapyUnacceptable toxicityII studyPartial responseAdvanced cancerClinical outcomes
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 3PatientsAntitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low–Expressing Advanced Breast Cancer: Results From a Phase Ib Study
Modi S, Park H, Murthy RK, Iwata H, Tamura K, Tsurutani J, Moreno-Aspitia A, Doi T, Sagara Y, Redfern C, Krop IE, Lee C, Fujisaki Y, Sugihara M, Zhang L, Shahidi J, Takahashi S. Antitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low–Expressing Advanced Breast Cancer: Results From a Phase Ib Study. Journal Of Clinical Oncology 2020, 38: 1887-1896. PMID: 32058843, PMCID: PMC7280051, DOI: 10.1200/jco.19.02318.Peer-Reviewed Original ResearchConceptsInterstitial lung diseaseHER2-low breast cancerT-DXdBreast cancerTrastuzumab deruxtecanAntitumor activityConfirmed objective response rateTopoisomerase I inhibitor payloadTreatment-emergent adverse eventsHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Breast cancer refractoryIndependent adjudication committeeObjective response ratePhase Ib studyAdvanced breast cancerGrowth factor receptor 2Preliminary antitumor activityIndependent central reviewWithdrawal of consentFactor receptor 2Cancer refractoryEligible patientsMetastatic HER2Unacceptable toxicity
2018
Phase II Study of Taselisib (GDC-0032) in Combination with Fulvestrant in Patients with HER2-Negative, Hormone Receptor–Positive Advanced Breast Cancer
Dickler MN, Saura C, Richards DA, Krop IE, Cervantes A, Bedard PL, Patel MR, Pusztai L, Oliveira M, Cardenas AK, Cui N, Wilson TR, Stout TJ, Wei MC, Hsu JY, Baselga J. Phase II Study of Taselisib (GDC-0032) in Combination with Fulvestrant in Patients with HER2-Negative, Hormone Receptor–Positive Advanced Breast Cancer. Clinical Cancer Research 2018, 24: 4380-4387. PMID: 29793946, PMCID: PMC6139036, DOI: 10.1158/1078-0432.ccr-18-0613.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsClass I Phosphatidylinositol 3-KinasesDisease-Free SurvivalDrug-Related Side Effects and Adverse ReactionsFemaleFulvestrantHumansImidazolesMiddle AgedMutationOxazepinesReceptor, ErbB-2Receptors, EstrogenConceptsAdverse eventsClinical activityBreast cancerMutation statusOpen-label phase II studyHR-positive breast cancerHigher objective response rateConfirmatory phase III trialNCI CTCAE v4.0Median treatment durationObjective response ratePhase II studySerious adverse eventsNew safety signalsPhase III trialsPositive breast cancerClin Cancer ResIntramuscular fulvestrantMeasurable diseaseRECIST v1.1II studyIII trialsPostmenopausal womenUnacceptable toxicityTumor response
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
2013
A phase II study of bevacizumab in combination with vinorelbine and trastuzumab in HER2-positive metastatic breast cancer
Lin NU, Seah DS, Gelman R, Desantis S, Mayer EL, Isakoff S, DiPiro P, Krop IE, Come SE, Weckstein D, Winer EP, Burstein HJ. A phase II study of bevacizumab in combination with vinorelbine and trastuzumab in HER2-positive metastatic breast cancer. Breast Cancer Research And Treatment 2013, 139: 403-410. PMID: 23645007, DOI: 10.1007/s10549-013-2551-9.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerGrade 3/4 non-hematologic toxicitiesHER2-positive metastatic breast cancerNon-hematologic toxicitiesTreatment-related toxicityBreast cancerCommon treatment-related toxicitiesFirst-line patientsProtocol-based therapySecond-line cohortSecond-line patientsSecond-line settingPhase II studyProportion of patientsCombination of vinorelbineCo-primary endpointsEligible patientsFebrile neutropeniaMedian PFSII studyMedian durationObjective responsePrior linesUnacceptable toxicityMedian age