Phase 3 Study of Talazoparib Plus Enzalutamide Versus Placebo Plus Enzalutamide as First‐Line Treatment in Patients With Metastatic Castration‐Resistant Prostate Cancer: TALAPRO‐2 Japanese Subgroup Analysis
ABSTRACT Background In TALAPRO‐2, the poly(ADP‐ribose) polymerase inhibitor talazoparib plus the androgen receptor–signaling inhibitor enzalutamide improved radiographic progression‐free survival (rPFS) versus placebo plus enzalutamide (hazard ratio [HR] = 0.63; 95% CI, 0.51–0.78) in molecularly uns...
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| Veröffentlicht in: | Cancer medicine (Malden, MA) MA), 2025-01, Vol.14 (1), p.e70333-n/a |
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| creator | Matsubara, Nobuaki Miyake, Hideaki Uemura, Hiroji Mizokami, Atsushi Kikukawa, Hiroaki Kosaka, Takeo Nishimura, Kazuo Nakamura, Motonobu Kobayashi, Kazuki Komaru, Atsushi Mori, Yuko Toyoizumi, Shigeyuki Hori, Natsuki Umeyama, Yoshiko Uemura, Hirotsugu |
| description | ABSTRACT
Background
In TALAPRO‐2, the poly(ADP‐ribose) polymerase inhibitor talazoparib plus the androgen receptor–signaling inhibitor enzalutamide improved radiographic progression‐free survival (rPFS) versus placebo plus enzalutamide (hazard ratio [HR] = 0.63; 95% CI, 0.51–0.78) in molecularly unselected patients with metastatic castration‐resistant prostate cancer (mCRPC). We report an exploratory analysis of efficacy, safety, and pharmacokinetics in Japanese patients enrolled in the TALAPRO‐2 study.
Methods
The ongoing, multinational, randomized, double‐blind, phase 3 TALAPRO‐2 study enrolled patients with mCRPC receiving ongoing androgen deprivation therapy. Patients were prospectively assessed for homologous recombination repair (HRR) gene alterations and randomized 1:1 to receive talazoparib or placebo plus enzalutamide once daily. The primary endpoint was rPFS by blinded independent central review (BICR). Secondary endpoints included overall survival, objective response, safety, and pharmacokinetics.
Results
For the 116 Japanese all‐comers patients enrolled in TALAPRO‐2, the HR for rPFS was 0.89 (95% CI, 0.45–1.75) for the talazoparib versus placebo arm; among those with HRR‐deficient disease, the HR was 0.58 (95% CI, 0.16–2.20). Among patients with BRCA1/2 gene alterations in the HRR‐deficient population (n = 10), the HR for rPFS was |
| doi_str_mv | 10.1002/cam4.70333 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11686335</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_2c9f88f6d1304bc88a05d52a931a4238</doaj_id><sourcerecordid>3150344352</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4043-4cb212234d2d8c27e12e22286a5444afbacac48b4032575b28bbbfef393376d43</originalsourceid><addsrcrecordid>eNp9ks1uEzEQx1cIRKvSCw-ALHFBSCn-2o9wQVHUQlGqrtoAR2vs9SaudtepvQtKTzwCD8cT8CRMklK1COGLR__5zV_j8STJc0aPGKX8jYFWHuVUCPEo2edUpqM8E_LxvXgvOYzxiuLJKc9y9jTZE-Nc5Knk-8nPcgnREkEu-6FaE1-TOTRw41cQnCZlM0Ry3N1AM_TQusqSzzZE1MoGjNX-HwBEcuJC7H99_zFznSXzYKFvbdcT15ESeodhJF9cvyRntofYo2TIFIOAke-w7sJGhzqWlMFvAIv5ztjwlswns0l5cY4QJx9hBZ3F5i8HvQh-WJFJB80aa58lT2pooj28vQ-STyfH8-mH0ez8_el0MhsZSaUYSaM541zIileF4bll3HLOiwxSKSXUGgwYWWhJBU_zVPNCa13bWoyFyLNKioPkdOdbebhSq-BaCGvlwamt4MNCQcDnNVZxM66Los4qJqjUpiiAplXKYSwYSC4K9Hq381oNurWVwTEFaB6YPsx0bqkW_qtiLCsyIVJ0eHXrEPz1YGOvWheNbRqckh-iEiylQkqRckRf_oVe-SHg9LaUzKnMxhvq9Y4y-A0x2PquG0bVZvnUZvnUdvkQfnG__zv0z6ohwHbAN9fY9X-s1HRyJnemvwFF6ulB</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3154704692</pqid></control><display><type>article</type><title>Phase 3 Study of Talazoparib Plus Enzalutamide Versus Placebo Plus Enzalutamide as First‐Line Treatment in Patients With Metastatic Castration‐Resistant Prostate Cancer: TALAPRO‐2 Japanese Subgroup Analysis</title><source>MEDLINE</source><source>Wiley Online Library Open Access</source><source>DOAJ Directory of Open Access Journals</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Matsubara, Nobuaki ; Miyake, Hideaki ; Uemura, Hiroji ; Mizokami, Atsushi ; Kikukawa, Hiroaki ; Kosaka, Takeo ; Nishimura, Kazuo ; Nakamura, Motonobu ; Kobayashi, Kazuki ; Komaru, Atsushi ; Mori, Yuko ; Toyoizumi, Shigeyuki ; Hori, Natsuki ; Umeyama, Yoshiko ; Uemura, Hirotsugu</creator><creatorcontrib>Matsubara, Nobuaki ; Miyake, Hideaki ; Uemura, Hiroji ; Mizokami, Atsushi ; Kikukawa, Hiroaki ; Kosaka, Takeo ; Nishimura, Kazuo ; Nakamura, Motonobu ; Kobayashi, Kazuki ; Komaru, Atsushi ; Mori, Yuko ; Toyoizumi, Shigeyuki ; Hori, Natsuki ; Umeyama, Yoshiko ; Uemura, Hirotsugu</creatorcontrib><description>ABSTRACT
Background
In TALAPRO‐2, the poly(ADP‐ribose) polymerase inhibitor talazoparib plus the androgen receptor–signaling inhibitor enzalutamide improved radiographic progression‐free survival (rPFS) versus placebo plus enzalutamide (hazard ratio [HR] = 0.63; 95% CI, 0.51–0.78) in molecularly unselected patients with metastatic castration‐resistant prostate cancer (mCRPC). We report an exploratory analysis of efficacy, safety, and pharmacokinetics in Japanese patients enrolled in the TALAPRO‐2 study.
Methods
The ongoing, multinational, randomized, double‐blind, phase 3 TALAPRO‐2 study enrolled patients with mCRPC receiving ongoing androgen deprivation therapy. Patients were prospectively assessed for homologous recombination repair (HRR) gene alterations and randomized 1:1 to receive talazoparib or placebo plus enzalutamide once daily. The primary endpoint was rPFS by blinded independent central review (BICR). Secondary endpoints included overall survival, objective response, safety, and pharmacokinetics.
Results
For the 116 Japanese all‐comers patients enrolled in TALAPRO‐2, the HR for rPFS was 0.89 (95% CI, 0.45–1.75) for the talazoparib versus placebo arm; among those with HRR‐deficient disease, the HR was 0.58 (95% CI, 0.16–2.20). Among patients with BRCA1/2 gene alterations in the HRR‐deficient population (n = 10), the HR for rPFS was < 0.01 (95% CI, < 0.01–not reached) for the talazoparib versus placebo arm. In the all‐comers population, the objective response rate by BICR was 55% (all complete responses) in the talazoparib arm versus 36% in the placebo arm. The safety profile of talazoparib plus enzalutamide was similar between Japanese patients and the overall all‐comers population; no new safety signals were identified. Anemia was the most common grade 3/4 treatment‐emergent adverse event (55%) and cause of talazoparib discontinuation (12%). Talazoparib Ctrough was comparable across Japanese, Asian, and non‐Asian subgroups.
Conclusions
In this exploratory analysis, efficacy outcomes with talazoparib plus enzalutamide in Japanese patients in TALAPRO‐2 were consistent with those in the overall all‐comers population. The safety profile and pharmacokinetics of the combination were similar between Japanese patients and the overall all‐comers population.
Trial Registration: ClinicalTrials.gov Identifier: NCT03395197</description><identifier>ISSN: 2045-7634</identifier><identifier>EISSN: 2045-7634</identifier><identifier>DOI: 10.1002/cam4.70333</identifier><identifier>PMID: 39737542</identifier><language>eng</language><publisher>United States: John Wiley & Sons, Inc</publisher><subject>Aged ; Aged, 80 and over ; Androgen receptors ; Androgens ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Benzamides - administration & dosage ; Benzamides - therapeutic use ; BRCA1 protein ; Cancer therapies ; Castration ; Chemotherapy ; Cytotoxicity ; Demographics ; Double-Blind Method ; East Asian People ; enzalutamide ; Homologous recombination ; Homologous recombination repair ; Humans ; Japan ; Japanese ; Male ; mCRPC ; Metastases ; Metastasis ; Middle Aged ; Nitriles - therapeutic use ; PARP inhibitor ; Pharmacokinetics ; Phenylthiohydantoin - administration & dosage ; Phenylthiohydantoin - adverse effects ; Phenylthiohydantoin - analogs & derivatives ; Phenylthiohydantoin - therapeutic use ; Phthalazines - administration & dosage ; Phthalazines - adverse effects ; Phthalazines - pharmacokinetics ; Phthalazines - therapeutic use ; Placebos ; Poly(ADP-ribose) Polymerase Inhibitors - administration & dosage ; Poly(ADP-ribose) Polymerase Inhibitors - adverse effects ; Poly(ADP-ribose) Polymerase Inhibitors - therapeutic use ; Population ; Progression-Free Survival ; Prostate cancer ; Prostatic Neoplasms, Castration-Resistant - drug therapy ; Prostatic Neoplasms, Castration-Resistant - mortality ; Prostatic Neoplasms, Castration-Resistant - pathology ; Safety ; Statistical analysis ; Survival ; TALAPRO‐2 ; talazoparib ; Tumors</subject><ispartof>Cancer medicine (Malden, MA), 2025-01, Vol.14 (1), p.e70333-n/a</ispartof><rights>2024 The Author(s). published by John Wiley & Sons Ltd.</rights><rights>2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.</rights><rights>2025. 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><cites>FETCH-LOGICAL-c4043-4cb212234d2d8c27e12e22286a5444afbacac48b4032575b28bbbfef393376d43</cites><orcidid>0000-0003-1919-2463 ; 0000-0003-4675-3975 ; 0000-0002-3665-9523 ; 0000-0002-7011-5263 ; 0000-0002-4371-4594 ; 0000-0002-9203-4245 ; 0000-0003-4967-0382</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11686335/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11686335/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,2096,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39737542$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Matsubara, Nobuaki</creatorcontrib><creatorcontrib>Miyake, Hideaki</creatorcontrib><creatorcontrib>Uemura, Hiroji</creatorcontrib><creatorcontrib>Mizokami, Atsushi</creatorcontrib><creatorcontrib>Kikukawa, Hiroaki</creatorcontrib><creatorcontrib>Kosaka, Takeo</creatorcontrib><creatorcontrib>Nishimura, Kazuo</creatorcontrib><creatorcontrib>Nakamura, Motonobu</creatorcontrib><creatorcontrib>Kobayashi, Kazuki</creatorcontrib><creatorcontrib>Komaru, Atsushi</creatorcontrib><creatorcontrib>Mori, Yuko</creatorcontrib><creatorcontrib>Toyoizumi, Shigeyuki</creatorcontrib><creatorcontrib>Hori, Natsuki</creatorcontrib><creatorcontrib>Umeyama, Yoshiko</creatorcontrib><creatorcontrib>Uemura, Hirotsugu</creatorcontrib><title>Phase 3 Study of Talazoparib Plus Enzalutamide Versus Placebo Plus Enzalutamide as First‐Line Treatment in Patients With Metastatic Castration‐Resistant Prostate Cancer: TALAPRO‐2 Japanese Subgroup Analysis</title><title>Cancer medicine (Malden, MA)</title><addtitle>Cancer Med</addtitle><description>ABSTRACT
Background
In TALAPRO‐2, the poly(ADP‐ribose) polymerase inhibitor talazoparib plus the androgen receptor–signaling inhibitor enzalutamide improved radiographic progression‐free survival (rPFS) versus placebo plus enzalutamide (hazard ratio [HR] = 0.63; 95% CI, 0.51–0.78) in molecularly unselected patients with metastatic castration‐resistant prostate cancer (mCRPC). We report an exploratory analysis of efficacy, safety, and pharmacokinetics in Japanese patients enrolled in the TALAPRO‐2 study.
Methods
The ongoing, multinational, randomized, double‐blind, phase 3 TALAPRO‐2 study enrolled patients with mCRPC receiving ongoing androgen deprivation therapy. Patients were prospectively assessed for homologous recombination repair (HRR) gene alterations and randomized 1:1 to receive talazoparib or placebo plus enzalutamide once daily. The primary endpoint was rPFS by blinded independent central review (BICR). Secondary endpoints included overall survival, objective response, safety, and pharmacokinetics.
Results
For the 116 Japanese all‐comers patients enrolled in TALAPRO‐2, the HR for rPFS was 0.89 (95% CI, 0.45–1.75) for the talazoparib versus placebo arm; among those with HRR‐deficient disease, the HR was 0.58 (95% CI, 0.16–2.20). Among patients with BRCA1/2 gene alterations in the HRR‐deficient population (n = 10), the HR for rPFS was < 0.01 (95% CI, < 0.01–not reached) for the talazoparib versus placebo arm. In the all‐comers population, the objective response rate by BICR was 55% (all complete responses) in the talazoparib arm versus 36% in the placebo arm. The safety profile of talazoparib plus enzalutamide was similar between Japanese patients and the overall all‐comers population; no new safety signals were identified. Anemia was the most common grade 3/4 treatment‐emergent adverse event (55%) and cause of talazoparib discontinuation (12%). Talazoparib Ctrough was comparable across Japanese, Asian, and non‐Asian subgroups.
Conclusions
In this exploratory analysis, efficacy outcomes with talazoparib plus enzalutamide in Japanese patients in TALAPRO‐2 were consistent with those in the overall all‐comers population. The safety profile and pharmacokinetics of the combination were similar between Japanese patients and the overall all‐comers population.
Trial Registration: ClinicalTrials.gov Identifier: NCT03395197</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Androgen receptors</subject><subject>Androgens</subject><subject>Antineoplastic Combined Chemotherapy Protocols - adverse effects</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Benzamides - administration & dosage</subject><subject>Benzamides - therapeutic use</subject><subject>BRCA1 protein</subject><subject>Cancer therapies</subject><subject>Castration</subject><subject>Chemotherapy</subject><subject>Cytotoxicity</subject><subject>Demographics</subject><subject>Double-Blind Method</subject><subject>East Asian People</subject><subject>enzalutamide</subject><subject>Homologous recombination</subject><subject>Homologous recombination repair</subject><subject>Humans</subject><subject>Japan</subject><subject>Japanese</subject><subject>Male</subject><subject>mCRPC</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Nitriles - therapeutic use</subject><subject>PARP inhibitor</subject><subject>Pharmacokinetics</subject><subject>Phenylthiohydantoin - administration & dosage</subject><subject>Phenylthiohydantoin - adverse effects</subject><subject>Phenylthiohydantoin - analogs & derivatives</subject><subject>Phenylthiohydantoin - therapeutic use</subject><subject>Phthalazines - administration & dosage</subject><subject>Phthalazines - adverse effects</subject><subject>Phthalazines - pharmacokinetics</subject><subject>Phthalazines - therapeutic use</subject><subject>Placebos</subject><subject>Poly(ADP-ribose) Polymerase Inhibitors - administration & dosage</subject><subject>Poly(ADP-ribose) Polymerase Inhibitors - adverse effects</subject><subject>Poly(ADP-ribose) Polymerase Inhibitors - therapeutic use</subject><subject>Population</subject><subject>Progression-Free Survival</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms, Castration-Resistant - drug therapy</subject><subject>Prostatic Neoplasms, Castration-Resistant - mortality</subject><subject>Prostatic Neoplasms, Castration-Resistant - pathology</subject><subject>Safety</subject><subject>Statistical analysis</subject><subject>Survival</subject><subject>TALAPRO‐2</subject><subject>talazoparib</subject><subject>Tumors</subject><issn>2045-7634</issn><issn>2045-7634</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2025</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNp9ks1uEzEQx1cIRKvSCw-ALHFBSCn-2o9wQVHUQlGqrtoAR2vs9SaudtepvQtKTzwCD8cT8CRMklK1COGLR__5zV_j8STJc0aPGKX8jYFWHuVUCPEo2edUpqM8E_LxvXgvOYzxiuLJKc9y9jTZE-Nc5Knk-8nPcgnREkEu-6FaE1-TOTRw41cQnCZlM0Ry3N1AM_TQusqSzzZE1MoGjNX-HwBEcuJC7H99_zFznSXzYKFvbdcT15ESeodhJF9cvyRntofYo2TIFIOAke-w7sJGhzqWlMFvAIv5ztjwlswns0l5cY4QJx9hBZ3F5i8HvQh-WJFJB80aa58lT2pooj28vQ-STyfH8-mH0ez8_el0MhsZSaUYSaM541zIileF4bll3HLOiwxSKSXUGgwYWWhJBU_zVPNCa13bWoyFyLNKioPkdOdbebhSq-BaCGvlwamt4MNCQcDnNVZxM66Los4qJqjUpiiAplXKYSwYSC4K9Hq381oNurWVwTEFaB6YPsx0bqkW_qtiLCsyIVJ0eHXrEPz1YGOvWheNbRqckh-iEiylQkqRckRf_oVe-SHg9LaUzKnMxhvq9Y4y-A0x2PquG0bVZvnUZvnUdvkQfnG__zv0z6ohwHbAN9fY9X-s1HRyJnemvwFF6ulB</recordid><startdate>202501</startdate><enddate>202501</enddate><creator>Matsubara, Nobuaki</creator><creator>Miyake, Hideaki</creator><creator>Uemura, Hiroji</creator><creator>Mizokami, Atsushi</creator><creator>Kikukawa, Hiroaki</creator><creator>Kosaka, Takeo</creator><creator>Nishimura, Kazuo</creator><creator>Nakamura, Motonobu</creator><creator>Kobayashi, Kazuki</creator><creator>Komaru, Atsushi</creator><creator>Mori, Yuko</creator><creator>Toyoizumi, Shigeyuki</creator><creator>Hori, Natsuki</creator><creator>Umeyama, Yoshiko</creator><creator>Uemura, Hirotsugu</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><general>Wiley</general><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-1919-2463</orcidid><orcidid>https://orcid.org/0000-0003-4675-3975</orcidid><orcidid>https://orcid.org/0000-0002-3665-9523</orcidid><orcidid>https://orcid.org/0000-0002-7011-5263</orcidid><orcidid>https://orcid.org/0000-0002-4371-4594</orcidid><orcidid>https://orcid.org/0000-0002-9203-4245</orcidid><orcidid>https://orcid.org/0000-0003-4967-0382</orcidid></search><sort><creationdate>202501</creationdate><title>Phase 3 Study of Talazoparib Plus Enzalutamide Versus Placebo Plus Enzalutamide as First‐Line Treatment in Patients With Metastatic Castration‐Resistant Prostate Cancer: TALAPRO‐2 Japanese Subgroup Analysis</title><author>Matsubara, Nobuaki ; Miyake, Hideaki ; Uemura, Hiroji ; Mizokami, Atsushi ; Kikukawa, Hiroaki ; Kosaka, Takeo ; Nishimura, Kazuo ; Nakamura, Motonobu ; Kobayashi, Kazuki ; Komaru, Atsushi ; Mori, Yuko ; Toyoizumi, Shigeyuki ; Hori, Natsuki ; Umeyama, Yoshiko ; Uemura, Hirotsugu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4043-4cb212234d2d8c27e12e22286a5444afbacac48b4032575b28bbbfef393376d43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Androgen receptors</topic><topic>Androgens</topic><topic>Antineoplastic Combined Chemotherapy Protocols - adverse effects</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Benzamides - administration & dosage</topic><topic>Benzamides - therapeutic use</topic><topic>BRCA1 protein</topic><topic>Cancer therapies</topic><topic>Castration</topic><topic>Chemotherapy</topic><topic>Cytotoxicity</topic><topic>Demographics</topic><topic>Double-Blind Method</topic><topic>East Asian People</topic><topic>enzalutamide</topic><topic>Homologous recombination</topic><topic>Homologous recombination repair</topic><topic>Humans</topic><topic>Japan</topic><topic>Japanese</topic><topic>Male</topic><topic>mCRPC</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Nitriles - therapeutic use</topic><topic>PARP inhibitor</topic><topic>Pharmacokinetics</topic><topic>Phenylthiohydantoin - administration & dosage</topic><topic>Phenylthiohydantoin - adverse effects</topic><topic>Phenylthiohydantoin - analogs & derivatives</topic><topic>Phenylthiohydantoin - therapeutic use</topic><topic>Phthalazines - administration & dosage</topic><topic>Phthalazines - adverse effects</topic><topic>Phthalazines - pharmacokinetics</topic><topic>Phthalazines - therapeutic use</topic><topic>Placebos</topic><topic>Poly(ADP-ribose) Polymerase Inhibitors - administration & dosage</topic><topic>Poly(ADP-ribose) Polymerase Inhibitors - adverse effects</topic><topic>Poly(ADP-ribose) Polymerase Inhibitors - therapeutic use</topic><topic>Population</topic><topic>Progression-Free Survival</topic><topic>Prostate cancer</topic><topic>Prostatic Neoplasms, Castration-Resistant - drug therapy</topic><topic>Prostatic Neoplasms, Castration-Resistant - mortality</topic><topic>Prostatic Neoplasms, Castration-Resistant - pathology</topic><topic>Safety</topic><topic>Statistical analysis</topic><topic>Survival</topic><topic>TALAPRO‐2</topic><topic>talazoparib</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Matsubara, Nobuaki</creatorcontrib><creatorcontrib>Miyake, Hideaki</creatorcontrib><creatorcontrib>Uemura, Hiroji</creatorcontrib><creatorcontrib>Mizokami, Atsushi</creatorcontrib><creatorcontrib>Kikukawa, Hiroaki</creatorcontrib><creatorcontrib>Kosaka, Takeo</creatorcontrib><creatorcontrib>Nishimura, Kazuo</creatorcontrib><creatorcontrib>Nakamura, Motonobu</creatorcontrib><creatorcontrib>Kobayashi, Kazuki</creatorcontrib><creatorcontrib>Komaru, Atsushi</creatorcontrib><creatorcontrib>Mori, Yuko</creatorcontrib><creatorcontrib>Toyoizumi, Shigeyuki</creatorcontrib><creatorcontrib>Hori, Natsuki</creatorcontrib><creatorcontrib>Umeyama, Yoshiko</creatorcontrib><creatorcontrib>Uemura, Hirotsugu</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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 Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Biological Science Database</collection><collection>Publicly Available Content 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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Cancer medicine (Malden, MA)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Matsubara, Nobuaki</au><au>Miyake, Hideaki</au><au>Uemura, Hiroji</au><au>Mizokami, Atsushi</au><au>Kikukawa, Hiroaki</au><au>Kosaka, Takeo</au><au>Nishimura, Kazuo</au><au>Nakamura, Motonobu</au><au>Kobayashi, Kazuki</au><au>Komaru, Atsushi</au><au>Mori, Yuko</au><au>Toyoizumi, Shigeyuki</au><au>Hori, Natsuki</au><au>Umeyama, Yoshiko</au><au>Uemura, Hirotsugu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phase 3 Study of Talazoparib Plus Enzalutamide Versus Placebo Plus Enzalutamide as First‐Line Treatment in Patients With Metastatic Castration‐Resistant Prostate Cancer: TALAPRO‐2 Japanese Subgroup Analysis</atitle><jtitle>Cancer medicine (Malden, MA)</jtitle><addtitle>Cancer Med</addtitle><date>2025-01</date><risdate>2025</risdate><volume>14</volume><issue>1</issue><spage>e70333</spage><epage>n/a</epage><pages>e70333-n/a</pages><issn>2045-7634</issn><eissn>2045-7634</eissn><abstract>ABSTRACT
Background
In TALAPRO‐2, the poly(ADP‐ribose) polymerase inhibitor talazoparib plus the androgen receptor–signaling inhibitor enzalutamide improved radiographic progression‐free survival (rPFS) versus placebo plus enzalutamide (hazard ratio [HR] = 0.63; 95% CI, 0.51–0.78) in molecularly unselected patients with metastatic castration‐resistant prostate cancer (mCRPC). We report an exploratory analysis of efficacy, safety, and pharmacokinetics in Japanese patients enrolled in the TALAPRO‐2 study.
Methods
The ongoing, multinational, randomized, double‐blind, phase 3 TALAPRO‐2 study enrolled patients with mCRPC receiving ongoing androgen deprivation therapy. Patients were prospectively assessed for homologous recombination repair (HRR) gene alterations and randomized 1:1 to receive talazoparib or placebo plus enzalutamide once daily. The primary endpoint was rPFS by blinded independent central review (BICR). Secondary endpoints included overall survival, objective response, safety, and pharmacokinetics.
Results
For the 116 Japanese all‐comers patients enrolled in TALAPRO‐2, the HR for rPFS was 0.89 (95% CI, 0.45–1.75) for the talazoparib versus placebo arm; among those with HRR‐deficient disease, the HR was 0.58 (95% CI, 0.16–2.20). Among patients with BRCA1/2 gene alterations in the HRR‐deficient population (n = 10), the HR for rPFS was < 0.01 (95% CI, < 0.01–not reached) for the talazoparib versus placebo arm. In the all‐comers population, the objective response rate by BICR was 55% (all complete responses) in the talazoparib arm versus 36% in the placebo arm. The safety profile of talazoparib plus enzalutamide was similar between Japanese patients and the overall all‐comers population; no new safety signals were identified. Anemia was the most common grade 3/4 treatment‐emergent adverse event (55%) and cause of talazoparib discontinuation (12%). Talazoparib Ctrough was comparable across Japanese, Asian, and non‐Asian subgroups.
Conclusions
In this exploratory analysis, efficacy outcomes with talazoparib plus enzalutamide in Japanese patients in TALAPRO‐2 were consistent with those in the overall all‐comers population. The safety profile and pharmacokinetics of the combination were similar between Japanese patients and the overall all‐comers population.
Trial Registration: ClinicalTrials.gov Identifier: NCT03395197</abstract><cop>United States</cop><pub>John Wiley & Sons, Inc</pub><pmid>39737542</pmid><doi>10.1002/cam4.70333</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0003-1919-2463</orcidid><orcidid>https://orcid.org/0000-0003-4675-3975</orcidid><orcidid>https://orcid.org/0000-0002-3665-9523</orcidid><orcidid>https://orcid.org/0000-0002-7011-5263</orcidid><orcidid>https://orcid.org/0000-0002-4371-4594</orcidid><orcidid>https://orcid.org/0000-0002-9203-4245</orcidid><orcidid>https://orcid.org/0000-0003-4967-0382</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2045-7634 |
| ispartof | Cancer medicine (Malden, MA), 2025-01, Vol.14 (1), p.e70333-n/a |
| issn | 2045-7634 2045-7634 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11686335 |
| source | MEDLINE; Wiley Online Library Open Access; DOAJ Directory of Open Access Journals; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Aged Aged, 80 and over Androgen receptors Androgens Antineoplastic Combined Chemotherapy Protocols - adverse effects Antineoplastic Combined Chemotherapy Protocols - therapeutic use Benzamides - administration & dosage Benzamides - therapeutic use BRCA1 protein Cancer therapies Castration Chemotherapy Cytotoxicity Demographics Double-Blind Method East Asian People enzalutamide Homologous recombination Homologous recombination repair Humans Japan Japanese Male mCRPC Metastases Metastasis Middle Aged Nitriles - therapeutic use PARP inhibitor Pharmacokinetics Phenylthiohydantoin - administration & dosage Phenylthiohydantoin - adverse effects Phenylthiohydantoin - analogs & derivatives Phenylthiohydantoin - therapeutic use Phthalazines - administration & dosage Phthalazines - adverse effects Phthalazines - pharmacokinetics Phthalazines - therapeutic use Placebos Poly(ADP-ribose) Polymerase Inhibitors - administration & dosage Poly(ADP-ribose) Polymerase Inhibitors - adverse effects Poly(ADP-ribose) Polymerase Inhibitors - therapeutic use Population Progression-Free Survival Prostate cancer Prostatic Neoplasms, Castration-Resistant - drug therapy Prostatic Neoplasms, Castration-Resistant - mortality Prostatic Neoplasms, Castration-Resistant - pathology Safety Statistical analysis Survival TALAPRO‐2 talazoparib Tumors |
| title | Phase 3 Study of Talazoparib Plus Enzalutamide Versus Placebo Plus Enzalutamide as First‐Line Treatment in Patients With Metastatic Castration‐Resistant Prostate Cancer: TALAPRO‐2 Japanese Subgroup Analysis |
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