Niraparib with androgen receptor-axis-targeted therapy in patients with metastatic castration-resistant prostate cancer: safety and pharmacokinetic results from a phase 1b study (BEDIVERE)
Purpose To assess the safety and pharmacokinetics and determine the recommended phase 2 dose (RP2D) of niraparib with apalutamide or abiraterone acetate plus prednisone (AAP) in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods BEDIVERE was a multicenter, open-label, pha...
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| Veröffentlicht in: | Cancer chemotherapy and pharmacology 2021-07, Vol.88 (1), p.25-37 |
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| creator | Saad, Fred Chi, Kim N. Shore, Neal D. Graff, Julie N. Posadas, Edwin M. Lattouf, Jean-Baptiste Espina, Byron M. Zhu, Eugene Yu, Alex Hazra, Anasuya De Meulder, Marc Mamidi, Rao N. V. S. Bradic, Branislav Francis, Peter Hayreh, Vinny Rezazadeh Kalebasty, Arash |
| description | Purpose
To assess the safety and pharmacokinetics and determine the recommended phase 2 dose (RP2D) of niraparib with apalutamide or abiraterone acetate plus prednisone (AAP) in patients with metastatic castration-resistant prostate cancer (mCRPC).
Methods
BEDIVERE was a multicenter, open-label, phase 1b study of niraparib 200 or 300 mg/day with apalutamide 240 mg or AAP (abiraterone acetate 1000 mg; prednisone 10 mg). Patients with mCRPC were previously treated with ≥ 2 lines of systemic therapy, including ≥ 1 androgen receptor-axis-targeted therapy for prostate cancer.
Results
Thirty-three patients were enrolled (niraparib-apalutamide, 6; niraparib-AAP, 27). No dose-limiting toxicities (DLTs) were reported when combinations included niraparib 200 mg; five patients receiving niraparib 300 mg experienced DLTs [niraparib-apalutamide, 2/3 patients (66.7%); niraparib-AAP, 3/8 patients (37.5%)]. Although data are limited, niraparib exposures were lower when given with apalutamide compared with historical niraparib monotherapy exposures in patients with solid tumors. Because of the higher incidence of DLTs, the niraparib–apalutamide combination and niraparib 300 mg combination with AAP were not further evaluated. Niraparib 200 mg was selected as the RP2D with AAP. Of 19 patients receiving niraparib 200 mg with AAP, 12 (63.2%) had grade 3/4 treatment-emergent adverse events, the most common being thrombocytopenia (26.3%) and hypertension (21.1%). Five patients (26.3%) had adverse events leading to treatment discontinuation.
Conclusions
These results support the choice of niraparib 200 mg as the RP2D with AAP. The niraparib–AAP combination was tolerable in patients with mCRPC, with no new safety signals. An ongoing phase 3 study is further assessing this combination in patients with mCRPC.
Trial registration no.
NCT02924766 (ClinicalTrials.gov). |
| doi_str_mv | 10.1007/s00280-021-04249-7 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8149334</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2531845449</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-f3e22c8517a01069c6f0c5ad4982a74d50f06e6ffc5b3262fc6948914be86e043</originalsourceid><addsrcrecordid>eNp9UcmO1DAQtRCIaRp-gAOyxAUOhvKSjcNIMDQw0ggkBFwtx6l0e-h2gu0A_W98HA4ZBrhwcqneUlV-hNzn8IQDVE8jgKiBgeAMlFANq26QFVdSMKiVvElWIJViRQXqhNyJ8RIAFJfyNjmRsioUr6sV-fHWBTOa4Fr6zaUdNb4LwxY9DWhxTENg5ruLLJmwxYQdTTvM_CN1no4mOfQpLsIDJhNTbllqcxFyNXgWMLrc9YmOYZhhzKi3GJ7RaHpMx3kgHXcmHIwdPjuPs0FWTfts3IfhQM0MR6S8pTFN3ZE-erF5ef5p837z-C651Zt9xHtX75p8fLX5cPaGXbx7fX72_IJZVanEeolC2LrglQEOZWPLHmxhOtXUwlSqK6CHEsu-t0UrRSl6WzaqbrhqsS4RlFyT08V3nNoDdjZfHcxej8EdTDjqwTj9L-LdTm-Hr7rmqpFyNnh4ZRCGLxPGpC-HKfi8sxaF5LUqVCauiVhYNv9VDNhfT-Cg58T1krjOietfiesqix78vdu15HfEmSAXQsyQ32L4M_s_tj8BALC70w</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2531845449</pqid></control><display><type>article</type><title>Niraparib with androgen receptor-axis-targeted therapy in patients with metastatic castration-resistant prostate cancer: safety and pharmacokinetic results from a phase 1b study (BEDIVERE)</title><source>SpringerNature Journals</source><creator>Saad, Fred ; Chi, Kim N. ; Shore, Neal D. ; Graff, Julie N. ; Posadas, Edwin M. ; Lattouf, Jean-Baptiste ; Espina, Byron M. ; Zhu, Eugene ; Yu, Alex ; Hazra, Anasuya ; De Meulder, Marc ; Mamidi, Rao N. V. S. ; Bradic, Branislav ; Francis, Peter ; Hayreh, Vinny ; Rezazadeh Kalebasty, Arash</creator><creatorcontrib>Saad, Fred ; Chi, Kim N. ; Shore, Neal D. ; Graff, Julie N. ; Posadas, Edwin M. ; Lattouf, Jean-Baptiste ; Espina, Byron M. ; Zhu, Eugene ; Yu, Alex ; Hazra, Anasuya ; De Meulder, Marc ; Mamidi, Rao N. V. S. ; Bradic, Branislav ; Francis, Peter ; Hayreh, Vinny ; Rezazadeh Kalebasty, Arash</creatorcontrib><description>Purpose
To assess the safety and pharmacokinetics and determine the recommended phase 2 dose (RP2D) of niraparib with apalutamide or abiraterone acetate plus prednisone (AAP) in patients with metastatic castration-resistant prostate cancer (mCRPC).
Methods
BEDIVERE was a multicenter, open-label, phase 1b study of niraparib 200 or 300 mg/day with apalutamide 240 mg or AAP (abiraterone acetate 1000 mg; prednisone 10 mg). Patients with mCRPC were previously treated with ≥ 2 lines of systemic therapy, including ≥ 1 androgen receptor-axis-targeted therapy for prostate cancer.
Results
Thirty-three patients were enrolled (niraparib-apalutamide, 6; niraparib-AAP, 27). No dose-limiting toxicities (DLTs) were reported when combinations included niraparib 200 mg; five patients receiving niraparib 300 mg experienced DLTs [niraparib-apalutamide, 2/3 patients (66.7%); niraparib-AAP, 3/8 patients (37.5%)]. Although data are limited, niraparib exposures were lower when given with apalutamide compared with historical niraparib monotherapy exposures in patients with solid tumors. Because of the higher incidence of DLTs, the niraparib–apalutamide combination and niraparib 300 mg combination with AAP were not further evaluated. Niraparib 200 mg was selected as the RP2D with AAP. Of 19 patients receiving niraparib 200 mg with AAP, 12 (63.2%) had grade 3/4 treatment-emergent adverse events, the most common being thrombocytopenia (26.3%) and hypertension (21.1%). Five patients (26.3%) had adverse events leading to treatment discontinuation.
Conclusions
These results support the choice of niraparib 200 mg as the RP2D with AAP. The niraparib–AAP combination was tolerable in patients with mCRPC, with no new safety signals. An ongoing phase 3 study is further assessing this combination in patients with mCRPC.
Trial registration no.
NCT02924766 (ClinicalTrials.gov).</description><identifier>ISSN: 0344-5704</identifier><identifier>EISSN: 1432-0843</identifier><identifier>DOI: 10.1007/s00280-021-04249-7</identifier><identifier>PMID: 33754187</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Acetic acid ; Adverse events ; Androgen receptors ; Androgens ; Cancer Research ; Castration ; Exposure ; Hypertension ; Medicine ; Medicine & Public Health ; Metastases ; Metastasis ; Oncology ; Original ; Original Article ; Pharmacokinetics ; Pharmacology ; Pharmacology/Toxicology ; Prednisone ; Prostate cancer ; Receiving ; Receptors ; Safety ; Solid tumors ; Therapy ; Thrombocytopenia ; Toxicity ; Tumors</subject><ispartof>Cancer chemotherapy and pharmacology, 2021-07, Vol.88 (1), p.25-37</ispartof><rights>The Author(s) 2021</rights><rights>The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-f3e22c8517a01069c6f0c5ad4982a74d50f06e6ffc5b3262fc6948914be86e043</citedby><cites>FETCH-LOGICAL-c474t-f3e22c8517a01069c6f0c5ad4982a74d50f06e6ffc5b3262fc6948914be86e043</cites><orcidid>0000-0003-2986-5617</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00280-021-04249-7$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00280-021-04249-7$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33754187$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Saad, Fred</creatorcontrib><creatorcontrib>Chi, Kim N.</creatorcontrib><creatorcontrib>Shore, Neal D.</creatorcontrib><creatorcontrib>Graff, Julie N.</creatorcontrib><creatorcontrib>Posadas, Edwin M.</creatorcontrib><creatorcontrib>Lattouf, Jean-Baptiste</creatorcontrib><creatorcontrib>Espina, Byron M.</creatorcontrib><creatorcontrib>Zhu, Eugene</creatorcontrib><creatorcontrib>Yu, Alex</creatorcontrib><creatorcontrib>Hazra, Anasuya</creatorcontrib><creatorcontrib>De Meulder, Marc</creatorcontrib><creatorcontrib>Mamidi, Rao N. V. S.</creatorcontrib><creatorcontrib>Bradic, Branislav</creatorcontrib><creatorcontrib>Francis, Peter</creatorcontrib><creatorcontrib>Hayreh, Vinny</creatorcontrib><creatorcontrib>Rezazadeh Kalebasty, Arash</creatorcontrib><title>Niraparib with androgen receptor-axis-targeted therapy in patients with metastatic castration-resistant prostate cancer: safety and pharmacokinetic results from a phase 1b study (BEDIVERE)</title><title>Cancer chemotherapy and pharmacology</title><addtitle>Cancer Chemother Pharmacol</addtitle><addtitle>Cancer Chemother Pharmacol</addtitle><description>Purpose
To assess the safety and pharmacokinetics and determine the recommended phase 2 dose (RP2D) of niraparib with apalutamide or abiraterone acetate plus prednisone (AAP) in patients with metastatic castration-resistant prostate cancer (mCRPC).
Methods
BEDIVERE was a multicenter, open-label, phase 1b study of niraparib 200 or 300 mg/day with apalutamide 240 mg or AAP (abiraterone acetate 1000 mg; prednisone 10 mg). Patients with mCRPC were previously treated with ≥ 2 lines of systemic therapy, including ≥ 1 androgen receptor-axis-targeted therapy for prostate cancer.
Results
Thirty-three patients were enrolled (niraparib-apalutamide, 6; niraparib-AAP, 27). No dose-limiting toxicities (DLTs) were reported when combinations included niraparib 200 mg; five patients receiving niraparib 300 mg experienced DLTs [niraparib-apalutamide, 2/3 patients (66.7%); niraparib-AAP, 3/8 patients (37.5%)]. Although data are limited, niraparib exposures were lower when given with apalutamide compared with historical niraparib monotherapy exposures in patients with solid tumors. Because of the higher incidence of DLTs, the niraparib–apalutamide combination and niraparib 300 mg combination with AAP were not further evaluated. Niraparib 200 mg was selected as the RP2D with AAP. Of 19 patients receiving niraparib 200 mg with AAP, 12 (63.2%) had grade 3/4 treatment-emergent adverse events, the most common being thrombocytopenia (26.3%) and hypertension (21.1%). Five patients (26.3%) had adverse events leading to treatment discontinuation.
Conclusions
These results support the choice of niraparib 200 mg as the RP2D with AAP. The niraparib–AAP combination was tolerable in patients with mCRPC, with no new safety signals. An ongoing phase 3 study is further assessing this combination in patients with mCRPC.
Trial registration no.
NCT02924766 (ClinicalTrials.gov).</description><subject>Acetic acid</subject><subject>Adverse events</subject><subject>Androgen receptors</subject><subject>Androgens</subject><subject>Cancer Research</subject><subject>Castration</subject><subject>Exposure</subject><subject>Hypertension</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Oncology</subject><subject>Original</subject><subject>Original Article</subject><subject>Pharmacokinetics</subject><subject>Pharmacology</subject><subject>Pharmacology/Toxicology</subject><subject>Prednisone</subject><subject>Prostate cancer</subject><subject>Receiving</subject><subject>Receptors</subject><subject>Safety</subject><subject>Solid tumors</subject><subject>Therapy</subject><subject>Thrombocytopenia</subject><subject>Toxicity</subject><subject>Tumors</subject><issn>0344-5704</issn><issn>1432-0843</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9UcmO1DAQtRCIaRp-gAOyxAUOhvKSjcNIMDQw0ggkBFwtx6l0e-h2gu0A_W98HA4ZBrhwcqneUlV-hNzn8IQDVE8jgKiBgeAMlFANq26QFVdSMKiVvElWIJViRQXqhNyJ8RIAFJfyNjmRsioUr6sV-fHWBTOa4Fr6zaUdNb4LwxY9DWhxTENg5ruLLJmwxYQdTTvM_CN1no4mOfQpLsIDJhNTbllqcxFyNXgWMLrc9YmOYZhhzKi3GJ7RaHpMx3kgHXcmHIwdPjuPs0FWTfts3IfhQM0MR6S8pTFN3ZE-erF5ef5p837z-C651Zt9xHtX75p8fLX5cPaGXbx7fX72_IJZVanEeolC2LrglQEOZWPLHmxhOtXUwlSqK6CHEsu-t0UrRSl6WzaqbrhqsS4RlFyT08V3nNoDdjZfHcxej8EdTDjqwTj9L-LdTm-Hr7rmqpFyNnh4ZRCGLxPGpC-HKfi8sxaF5LUqVCauiVhYNv9VDNhfT-Cg58T1krjOietfiesqix78vdu15HfEmSAXQsyQ32L4M_s_tj8BALC70w</recordid><startdate>20210701</startdate><enddate>20210701</enddate><creator>Saad, Fred</creator><creator>Chi, Kim N.</creator><creator>Shore, Neal D.</creator><creator>Graff, Julie N.</creator><creator>Posadas, Edwin M.</creator><creator>Lattouf, Jean-Baptiste</creator><creator>Espina, Byron M.</creator><creator>Zhu, Eugene</creator><creator>Yu, Alex</creator><creator>Hazra, Anasuya</creator><creator>De Meulder, Marc</creator><creator>Mamidi, Rao N. V. S.</creator><creator>Bradic, Branislav</creator><creator>Francis, Peter</creator><creator>Hayreh, Vinny</creator><creator>Rezazadeh Kalebasty, Arash</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2986-5617</orcidid></search><sort><creationdate>20210701</creationdate><title>Niraparib with androgen receptor-axis-targeted therapy in patients with metastatic castration-resistant prostate cancer: safety and pharmacokinetic results from a phase 1b study (BEDIVERE)</title><author>Saad, Fred ; Chi, Kim N. ; Shore, Neal D. ; Graff, Julie N. ; Posadas, Edwin M. ; Lattouf, Jean-Baptiste ; Espina, Byron M. ; Zhu, Eugene ; Yu, Alex ; Hazra, Anasuya ; De Meulder, Marc ; Mamidi, Rao N. V. S. ; Bradic, Branislav ; Francis, Peter ; Hayreh, Vinny ; Rezazadeh Kalebasty, Arash</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-f3e22c8517a01069c6f0c5ad4982a74d50f06e6ffc5b3262fc6948914be86e043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Acetic acid</topic><topic>Adverse events</topic><topic>Androgen receptors</topic><topic>Androgens</topic><topic>Cancer Research</topic><topic>Castration</topic><topic>Exposure</topic><topic>Hypertension</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Oncology</topic><topic>Original</topic><topic>Original Article</topic><topic>Pharmacokinetics</topic><topic>Pharmacology</topic><topic>Pharmacology/Toxicology</topic><topic>Prednisone</topic><topic>Prostate cancer</topic><topic>Receiving</topic><topic>Receptors</topic><topic>Safety</topic><topic>Solid tumors</topic><topic>Therapy</topic><topic>Thrombocytopenia</topic><topic>Toxicity</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Saad, Fred</creatorcontrib><creatorcontrib>Chi, Kim N.</creatorcontrib><creatorcontrib>Shore, Neal D.</creatorcontrib><creatorcontrib>Graff, Julie N.</creatorcontrib><creatorcontrib>Posadas, Edwin M.</creatorcontrib><creatorcontrib>Lattouf, Jean-Baptiste</creatorcontrib><creatorcontrib>Espina, Byron M.</creatorcontrib><creatorcontrib>Zhu, Eugene</creatorcontrib><creatorcontrib>Yu, Alex</creatorcontrib><creatorcontrib>Hazra, Anasuya</creatorcontrib><creatorcontrib>De Meulder, Marc</creatorcontrib><creatorcontrib>Mamidi, Rao N. V. S.</creatorcontrib><creatorcontrib>Bradic, Branislav</creatorcontrib><creatorcontrib>Francis, Peter</creatorcontrib><creatorcontrib>Hayreh, Vinny</creatorcontrib><creatorcontrib>Rezazadeh Kalebasty, Arash</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer chemotherapy and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Saad, Fred</au><au>Chi, Kim N.</au><au>Shore, Neal D.</au><au>Graff, Julie N.</au><au>Posadas, Edwin M.</au><au>Lattouf, Jean-Baptiste</au><au>Espina, Byron M.</au><au>Zhu, Eugene</au><au>Yu, Alex</au><au>Hazra, Anasuya</au><au>De Meulder, Marc</au><au>Mamidi, Rao N. V. S.</au><au>Bradic, Branislav</au><au>Francis, Peter</au><au>Hayreh, Vinny</au><au>Rezazadeh Kalebasty, Arash</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Niraparib with androgen receptor-axis-targeted therapy in patients with metastatic castration-resistant prostate cancer: safety and pharmacokinetic results from a phase 1b study (BEDIVERE)</atitle><jtitle>Cancer chemotherapy and pharmacology</jtitle><stitle>Cancer Chemother Pharmacol</stitle><addtitle>Cancer Chemother Pharmacol</addtitle><date>2021-07-01</date><risdate>2021</risdate><volume>88</volume><issue>1</issue><spage>25</spage><epage>37</epage><pages>25-37</pages><issn>0344-5704</issn><eissn>1432-0843</eissn><abstract>Purpose
To assess the safety and pharmacokinetics and determine the recommended phase 2 dose (RP2D) of niraparib with apalutamide or abiraterone acetate plus prednisone (AAP) in patients with metastatic castration-resistant prostate cancer (mCRPC).
Methods
BEDIVERE was a multicenter, open-label, phase 1b study of niraparib 200 or 300 mg/day with apalutamide 240 mg or AAP (abiraterone acetate 1000 mg; prednisone 10 mg). Patients with mCRPC were previously treated with ≥ 2 lines of systemic therapy, including ≥ 1 androgen receptor-axis-targeted therapy for prostate cancer.
Results
Thirty-three patients were enrolled (niraparib-apalutamide, 6; niraparib-AAP, 27). No dose-limiting toxicities (DLTs) were reported when combinations included niraparib 200 mg; five patients receiving niraparib 300 mg experienced DLTs [niraparib-apalutamide, 2/3 patients (66.7%); niraparib-AAP, 3/8 patients (37.5%)]. Although data are limited, niraparib exposures were lower when given with apalutamide compared with historical niraparib monotherapy exposures in patients with solid tumors. Because of the higher incidence of DLTs, the niraparib–apalutamide combination and niraparib 300 mg combination with AAP were not further evaluated. Niraparib 200 mg was selected as the RP2D with AAP. Of 19 patients receiving niraparib 200 mg with AAP, 12 (63.2%) had grade 3/4 treatment-emergent adverse events, the most common being thrombocytopenia (26.3%) and hypertension (21.1%). Five patients (26.3%) had adverse events leading to treatment discontinuation.
Conclusions
These results support the choice of niraparib 200 mg as the RP2D with AAP. The niraparib–AAP combination was tolerable in patients with mCRPC, with no new safety signals. An ongoing phase 3 study is further assessing this combination in patients with mCRPC.
Trial registration no.
NCT02924766 (ClinicalTrials.gov).</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>33754187</pmid><doi>10.1007/s00280-021-04249-7</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0003-2986-5617</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0344-5704 |
| ispartof | Cancer chemotherapy and pharmacology, 2021-07, Vol.88 (1), p.25-37 |
| issn | 0344-5704 1432-0843 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8149334 |
| source | SpringerNature Journals |
| subjects | Acetic acid Adverse events Androgen receptors Androgens Cancer Research Castration Exposure Hypertension Medicine Medicine & Public Health Metastases Metastasis Oncology Original Original Article Pharmacokinetics Pharmacology Pharmacology/Toxicology Prednisone Prostate cancer Receiving Receptors Safety Solid tumors Therapy Thrombocytopenia Toxicity Tumors |
| title | Niraparib with androgen receptor-axis-targeted therapy in patients with metastatic castration-resistant prostate cancer: safety and pharmacokinetic results from a phase 1b study (BEDIVERE) |
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