{"id":"https://openalex.org/W4361946292","doi":"https://doi.org/10.1158/1078-0432.c.6527073","title":"Data from Differential Toxicity in Patients with and without DNA Repair Mutations: Phase I Study of Carboplatin and Talazoparib in Advanced Solid Tumors","display_name":"Data from Differential Toxicity in Patients with and without DNA Repair Mutations: Phase I Study of Carboplatin and Talazoparib in Advanced Solid Tumors","publication_year":2023,"publication_date":"2023-03-31","ids":{"openalex":"https://openalex.org/W4361946292","doi":"https://doi.org/10.1158/1078-0432.c.6527073"},"language":"en","primary_location":{"id":"doi:10.1158/1078-0432.c.6527073","doi":"https://doi.org/10.1158/1078-0432.c.6527073","is_oa":true,"landing_page_url":"http://dx.doi.org/10.1158/1078-0432.c.6527073","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"},"volume":null,"type":"other","is_traditional":false,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"http://dx.doi.org/10.1158/1078-0432.c.6527073","any_repository_has_fulltext":null},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5000765851","display_name":"Mallika Sachdev Dhawan","orcid":"https://orcid.org/0000-0001-8338-4238","observed_orcids":["https://orcid.org/0000-0001-8338-4238"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Mallika S. Dhawan","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5110967121","display_name":"Imke Heleen Bartelink","orcid":"https://orcid.org/0000-0001-9602-3407","observed_orcids":["https://orcid.org/0000-0001-9602-3407"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Imke H. Bartelink","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5081123075","display_name":"Rahul Raj Aggarwal","orcid":"https://orcid.org/0000-0001-7003-7982","observed_orcids":["https://orcid.org/0000-0001-7003-7982"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Rahul Raj Aggarwal","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5039935336","display_name":"Jim X Leng","orcid":"https://orcid.org/0000-0001-8482-4776","observed_orcids":["https://orcid.org/0000-0001-8482-4776"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Jim Leng","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5009681280","display_name":"Jenna Z. Zhang","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Jenna Z. Zhang","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5034011414","display_name":"Nela Paw\u0142owska","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Nela Pawlowska","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5052676933","display_name":"Manuela Terranova-Barberio","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Manuela Terranova-Barberio","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5004633925","display_name":"Jennifer Ann Grabowsky","orcid":"https://orcid.org/0000-0003-4871-0741","observed_orcids":["https://orcid.org/0000-0003-4871-0741"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Jennifer A. Grabowsky","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5059751620","display_name":"Andrew D. Gewitz","orcid":"https://orcid.org/0009-0005-5362-5324","observed_orcids":["https://orcid.org/0009-0005-5362-5324"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Andrew Gewitz","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5053577410","display_name":"Amy Jo Chien","orcid":"https://orcid.org/0000-0003-2978-6249","observed_orcids":["https://orcid.org/0000-0003-2978-6249"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Amy J. Chien","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5006839105","display_name":"Mark M. Moasser","orcid":"https://orcid.org/0000-0003-4411-4336","observed_orcids":["https://orcid.org/0000-0003-4411-4336"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Mark Moasser","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5019481117","display_name":"Robin Kate Kelley","orcid":"https://orcid.org/0000-0002-1984-2430","observed_orcids":["https://orcid.org/0000-0002-1984-2430"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Robin K. Kelley","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5022324089","display_name":"Tayeba Maktabi","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Tayeba Maktabi","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":null,"display_name":"Scott Thomas","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Scott Thomas","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5083373965","display_name":"Pamela N. M\u00fcnster","orcid":"https://orcid.org/0000-0002-2074-0984","observed_orcids":["https://orcid.org/0000-0002-2074-0984","https://orcid.org/0009-0009-4141-2312"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Pamela N. Munster","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11914","display_name":"PARP inhibition in cancer therapy","score":1.0,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T11914","display_name":"PARP inhibition in cancer therapy","score":1.0,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10769","display_name":"BRCA gene mutations in cancer","score":0.0,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12829","display_name":"Advanced Breast Cancer Therapies","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/talazoparib","display_name":"talazoparib","score":0.9909999966621399},{"id":"https://openalex.org/keywords/carboplatin","display_name":"carboplatin","score":1.0},{"id":"https://openalex.org/keywords/parp-inhibitors","display_name":"PARP inhibitors","score":0.8769999742507935},{"id":"https://openalex.org/keywords/dna-repair-mutations","display_name":"DNA repair mutations","score":0.8679999709129333},{"id":"https://openalex.org/keywords/hematological-toxicity","display_name":"hematologic toxicity","score":0.7940000295639038},{"id":"https://openalex.org/keywords/neutropenia","display_name":"neutropenia","score":0.9559999704360962},{"id":"https://openalex.org/keywords/thrombocytopenia","display_name":"thrombocytopenia","score":0.9760000109672546},{"id":"https://openalex.org/keywords/intermittent-dosing","display_name":"intermittent dosing","score":0.7839999794960022},{"id":"https://openalex.org/keywords/advanced-solid-tumors","display_name":"advanced solid tumors","score":0.875},{"id":"https://openalex.org/keywords/platinum-refractory-disease","display_name":"platinum-refractory disease","score":0.656000018119812},{"id":"https://openalex.org/keywords/combination-chemotherapy","display_name":"combination chemotherapy","score":0.5659999847412109}],"concepts":[{"id":"https://openalex.org/C2781451048","wikidata":"https://www.wikidata.org/wiki/Q415588","display_name":"Carboplatin","level":4,"score":0.8864187002182007},{"id":"https://openalex.org/C2778375690","wikidata":"https://www.wikidata.org/wiki/Q7814214","display_name":"Tolerability","level":3,"score":0.6545825600624084},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.653499960899353},{"id":"https://openalex.org/C2777063308","wikidata":"https://www.wikidata.org/wiki/Q1435822","display_name":"Neutropenia","level":3,"score":0.6450707912445068},{"id":"https://openalex.org/C29730261","wikidata":"https://www.wikidata.org/wiki/Q274160","display_name":"Toxicity","level":2,"score":0.6293644905090332},{"id":"https://openalex.org/C112705442","wikidata":"https://www.wikidata.org/wiki/Q323936","display_name":"Pharmacokinetics","level":2,"score":0.5812884569168091},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.5472119450569153},{"id":"https://openalex.org/C2778248108","wikidata":"https://www.wikidata.org/wiki/Q5445","display_name":"Anemia","level":2,"score":0.47305646538734436},{"id":"https://openalex.org/C90924648","wikidata":"https://www.wikidata.org/wiki/Q120569","display_name":"Gastroenterology","level":1,"score":0.4338083565235138},{"id":"https://openalex.org/C2779138821","wikidata":"https://www.wikidata.org/wiki/Q7118227","display_name":"PARP inhibitor","level":5,"score":0.41851332783699036},{"id":"https://openalex.org/C2776694085","wikidata":"https://www.wikidata.org/wiki/Q974135","display_name":"Chemotherapy","level":2,"score":0.3809352517127991},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.3668985068798065},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.35472336411476135},{"id":"https://openalex.org/C197934379","wikidata":"https://www.wikidata.org/wiki/Q2047938","display_name":"Adverse effect","level":2,"score":0.1514815092086792},{"id":"https://openalex.org/C2778239845","wikidata":"https://www.wikidata.org/wiki/Q412415","display_name":"Cisplatin","level":3,"score":0.15145134925842285},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.130473792552948},{"id":"https://openalex.org/C182979987","wikidata":"https://www.wikidata.org/wiki/Q3907241","display_name":"Poly ADP ribose polymerase","level":4,"score":0.06303474307060242},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.0},{"id":"https://openalex.org/C82381507","wikidata":"https://www.wikidata.org/wiki/Q416878","display_name":"Polymerase","level":3,"score":0.0},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0}],"mesh":[],"locations_count":2,"locations":[{"id":"doi:10.1158/1078-0432.c.6527073","doi":"https://doi.org/10.1158/1078-0432.c.6527073","is_oa":true,"landing_page_url":"http://dx.doi.org/10.1158/1078-0432.c.6527073","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"},{"id":"doi:10.1158/1078-0432.c.6527073.v1","doi":"https://doi.org/10.1158/1078-0432.c.6527073.v1","is_oa":true,"landing_page_url":"https://doi.org/10.1158/1078-0432.c.6527073.v1","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.1158/1078-0432.c.6527073","doi":"https://doi.org/10.1158/1078-0432.c.6527073","is_oa":true,"landing_page_url":"http://dx.doi.org/10.1158/1078-0432.c.6527073","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"},"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":1.0}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2744945030","https://openalex.org/W2656653322","https://openalex.org/W2889923191","https://openalex.org/W2886359671","https://openalex.org/W2476731978","https://openalex.org/W2592005098","https://openalex.org/W4242588491","https://openalex.org/W4223562117","https://openalex.org/W3169161004","https://openalex.org/W4392702868"],"abstract_inverted_index":{"Abstract":[0],"Purpose:":[1],"The":[2],"PARP":[3,211],"inhibitor":[4],"(PARPi)":[5],"talazoparib":[6,34,68,175,229,252],"may":[7,218],"potentiate":[8],"activity":[9],"of":[10,33,150,167,210,223],"chemotherapy":[11],"and":[12,31,35,44,64,69,74,97,116,131,174,192,228,257],"toxicity":[13,160,202,239],"in":[14,59,126,136,155,189,196,232,243],"cells":[15],"vulnerable":[16],"to":[17],"DNA":[18,42,156,233,259],"damage.":[19],"Experimental":[20],"Design:":[21],"This":[22],"phase":[23],"I":[24],"study":[25],"evaluated":[26],"the":[27,101,220],"safety,":[28],"tolerability,":[29],"pharmacokinetics,":[30],"efficacy":[32,231],"carboplatin.":[36],"Pharmacokinetic":[37,159,201],"modeling":[38,161,203],"explored":[39],"associations":[40],"between":[41],"vulnerability":[43],"hematologic":[45,238],"toxicity.":[46],"Results:":[47],"Twenty-four":[48],"patients":[49,85,142],"(eight":[50],"males;":[51],"16":[52],"females)":[53],"with":[54,87,250],"solid":[55],"tumors":[56],"were":[57,124],"enrolled":[58],"four":[60],"cohorts":[61],"at":[62],"0.75":[63],"1":[65,73,176],"mg":[66,177],"daily":[67],"weekly":[70],"carboplatin":[71,168],"(AUC":[72],"1.5,":[75],"every":[76,80,171],"2":[77],"weeks":[78,173],"or":[79],"3":[81,95,172],"weeks),":[82],"including":[83],"14":[84],"(58%)":[86],"prior":[88],"platinum":[89],"treatment.":[90],"Dose-limiting":[91],"toxicities":[92,108],"included":[93,109],"grade":[94,98],"fatigue":[96,110],"4":[99,147],"thrombocytopenia;":[100],"MTD":[102],"was":[103,240],"not":[104],"reached.":[105],"Grade":[106],"3/4":[107],"(13%),":[111],"neutropenia":[112],"(63%),":[113],"thrombocytopenia":[114],"(29%),":[115],"anemia":[117],"(38%).":[118],"After":[119],"cycle":[120],"2's":[121],"dose,":[122],"delays/reductions":[123],"required":[125],"all":[127],"patients.":[128,140],"One":[129],"complete":[130],"two":[132],"partial":[133],"responses":[134],"occurred":[135],"germline":[137,256],"BRCA1/2":[138],"(gBRCA1/2)":[139],"Four":[141],"showed":[143,230],"stable":[144],"disease":[145],"beyond":[146],"months,":[148],"three":[149,165],"which":[151],"had":[152],"known":[153],"mutations":[154],"repair":[157],"pathways.":[158],"suggests":[162,204],"that":[163],"after":[164],"cycles":[166],"AUC":[169],"1.5":[170],"daily,":[178],"neutrophil":[179],"counts":[180],"decreased":[181],"78%":[182],"[confidence":[183],"interval":[184],"(CI),":[185],"87\u201368]":[186],"from":[187],"baseline":[188],"gBRCA":[190,215,244],"carriers":[191],"63%":[193],"(CI,":[194],"72\u201355)":[195],"noncarriers":[197],"(P":[198],"<":[199],"0.001).":[200],"an":[205],"intermittent,":[206],"pulse":[207],"dosing":[208,253],"schedule":[209],"inhibition,":[212],"differentiated":[213,254],"by":[214,255],"mutation":[216,235,261],"status,":[217],"improve":[219],"benefit/risk":[221],"ratio":[222],"combination":[224],"therapy.":[225],"Conclusions:":[226],"Carboplatin":[227,246],"damage":[234,260],"carriers,":[236],"but":[237],"more":[241],"pronounced":[242],"carriers.":[245,262],"is":[247],"best":[248],"combined":[249],"intermittent":[251],"somatic":[258],"Clin":[263],"Cancer":[264],"Res;":[265],"23(21);":[266],"6400\u201310.":[267],"\u00a92017":[268],"AACR.":[269]},"counts_by_year":[],"updated_date":"2026-11-09T13:22:03.289127","created_date":"2023-04-05T00:00:00"}