2023
Quantitative DNA Repair Biomarkers and Immune Profiling for Temozolomide and Olaparib in Metastatic Colorectal Cancer
Cecchini M, Zhang J, Wei W, Sklar J, Lacy J, Zhong M, Kong Y, Zhao H, DiPalermo J, Devine L, Stein S, Kortmansky J, Johung K, Bindra R, LoRusso P, Schalper K. Quantitative DNA Repair Biomarkers and Immune Profiling for Temozolomide and Olaparib in Metastatic Colorectal Cancer. Cancer Research Communications 2023, 3: 1132-1139. PMID: 37387791, PMCID: PMC10305782, DOI: 10.1158/2767-9764.crc-23-0045.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingMGMT protein expressionColorectal cancerStable diseaseQuantitative immunofluorescenceT cellsProtein expressionPromoter hypermethylationLow MGMT protein expressionPARP inhibitorsRadiographic tumor regressionMetastatic colorectal cancerAdvanced colorectal cancerPretreatment tumor biopsiesEffector T cellsTumor-infiltrating lymphocytesMGMT proteinDNA repair biomarkersBaseline CD8Eligible patientsIncreased CD8Methylguanine-DNA methyltransferaseObjective responseProgressive diseaseImmune markers
2020
A phase 1b expansion study of TAS‐102 with oxaliplatin for refractory metastatic colorectal cancer
Cecchini M, Kortmansky JS, Cui C, Wei W, Thumar JR, Uboha NV, Hafez N, Lacy J, Fischbach NA, Sabbath KD, Gomez CM, Sporn JR, Stein S, Hochster HS. A phase 1b expansion study of TAS‐102 with oxaliplatin for refractory metastatic colorectal cancer. Cancer 2020, 127: 1417-1424. PMID: 33351187, PMCID: PMC8085021, DOI: 10.1002/cncr.33379.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsColorectal NeoplasmsDrug Administration ScheduleDrug CombinationsDrug Resistance, NeoplasmFemaleFluorouracilHumansIrinotecanLeucovorinMaleMiddle AgedOrganoplatinum CompoundsOxaliplatinProgression-Free SurvivalPyrrolidinesResponse Evaluation Criteria in Solid TumorsThymineTrifluridineConceptsMetastatic colorectal cancerOverall response rateRefractory metastatic colorectal cancerProgression-free survivalTAS-102Colorectal cancerDay 1Primary endpointOverall survivalDose escalationDay 5Median progression-free survivalPhase 1b studyMedian overall survivalResponse Evaluation CriteriaTreat populationDose expansionPartial responseStandard dosesUnexpected side effectsStudy treatmentTumor shrinkageUnexpected toxicitiesSide effectsNovel antimetabolite
2019
Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial
Eng C, Kim T, Bendell J, Argilés G, Tebbutt N, Di Bartolomeo M, Falcone A, Fakih M, Kozloff M, Segal N, Sobrero A, Yan Y, Chang I, Uyei A, Roberts L, Ciardiello F, Investigators I, Ahn J, Asselah J, Badarinath S, Baijal S, Begbie S, Berry S, Canon J, Carbone R, Cervantes A, Cha Y, Chang K, Chaudhry A, Chmielowska E, Cho S, Chu D, Couture F, Cultrera J, Cunningham D, Van Cutsem E, Cuyle P, Davies J, Dowden S, Dvorkin M, Ganju V, Garcia R, Kerr R, Kim T, King K, Kortmansky J, Kozloff M, Lam K, Lee J, Lee A, Lesperance B, Luppi G, Ma B, Maiello E, Mandanas R, Marshall J, Marx G, Mullamitha S, Nechaeva M, Park J, Pavlakis N, Ponce C, Potemski P, Raouf S, Reeves J, Segal N, Siena S, Smolin A, Streb J, Strickland A, Szutowicz-Zielinska E, Tabernero J, Tan B, Valera J, Van den Eynde M, Vergauwe P, Vickers M, Womack M, Wroblewska M, Young R. Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial. The Lancet Oncology 2019, 20: 849-861. PMID: 31003911, DOI: 10.1016/s1470-2045(19)30027-0.Peer-Reviewed Original ResearchConceptsMetastatic colorectal cancerMicrosatellite-stable metastatic colorectal cancerRegorafenib groupOverall survivalColorectal cancerAdverse eventsCombination groupAtezolizumab groupAtezolizumab monotherapyOpen-labelBaseline Eastern Cooperative Oncology Group performance statusEndpoint of improving overall survivalEastern Cooperative Oncology Group performance statusAll-cause grade 3Increased blood creatine phosphokinaseTreat metastatic colorectal cancerIntention-to-treat populationControlled trialsSafety of atezolizumabSystemic chemotherapy regimensThird-line settingMedian overall survivalTreatment-related deathsImmunotherapy to patientsMedian follow-up