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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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.70333 |
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| author | Nobuaki Matsubara Hideaki Miyake Hiroji Uemura Atsushi Mizokami Hiroaki Kikukawa Takeo Kosaka Kazuo Nishimura Motonobu Nakamura Kazuki Kobayashi Atsushi Komaru Yuko Mori Shigeyuki Toyoizumi Natsuki Hori Yoshiko Umeyama Hirotsugu Uemura |
| author_facet | Nobuaki Matsubara Hideaki Miyake Hiroji Uemura Atsushi Mizokami Hiroaki Kikukawa Takeo Kosaka Kazuo Nishimura Motonobu Nakamura Kazuki Kobayashi Atsushi Komaru Yuko Mori Shigeyuki Toyoizumi Natsuki Hori Yoshiko Umeyama Hirotsugu Uemura |
| author_sort | Nobuaki Matsubara |
| collection | DOAJ |
| 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 |
| format | Article |
| id | doaj-art-2c9f88f6d1304bc88a05d52a931a4238 |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-2c9f88f6d1304bc88a05d52a931a42382025-01-13T13:22:38ZengWileyCancer Medicine2045-76342025-01-01141n/an/a10.1002/cam4.70333Phase 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 AnalysisNobuaki Matsubara0Hideaki Miyake1Hiroji Uemura2Atsushi Mizokami3Hiroaki Kikukawa4Takeo Kosaka5Kazuo Nishimura6Motonobu Nakamura7Kazuki Kobayashi8Atsushi Komaru9Yuko Mori10Shigeyuki Toyoizumi11Natsuki Hori12Yoshiko Umeyama13Hirotsugu Uemura14National Cancer Center Hospital East Kashiwa JapanHamamatsu University School of Medicine Hamamatsu JapanYokohama City University Medical Center Yokohama JapanKanazawa University Hospital Kanazawa JapanKumamoto Medical Center Kumamoto JapanKeio University Hospital Tokyo JapanOsaka International Cancer Institute Osaka JapanKyushu Cancer Center Fukuoka JapanYokosuka Kyosai Hospital Yokosuka JapanChiba Cancer Center Chiba JapanPfizer R&D Japan Tokyo JapanPfizer R&D Japan Tokyo JapanPfizer R&D Japan Tokyo JapanPfizer R&D Japan Tokyo JapanKindai University Hospital Osaka JapanABSTRACT 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: NCT03395197https://doi.org/10.1002/cam4.70333enzalutamideJapanesemCRPCPARP inhibitorTALAPRO‐2talazoparib |
| spellingShingle | Nobuaki Matsubara Hideaki Miyake Hiroji Uemura Atsushi Mizokami Hiroaki Kikukawa Takeo Kosaka Kazuo Nishimura Motonobu Nakamura Kazuki Kobayashi Atsushi Komaru Yuko Mori Shigeyuki Toyoizumi Natsuki Hori Yoshiko Umeyama Hirotsugu Uemura 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 Cancer Medicine enzalutamide Japanese mCRPC PARP inhibitor TALAPRO‐2 talazoparib |
| 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_full | 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_fullStr | 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_full_unstemmed | 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_short | 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_sort | 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 |
| topic | enzalutamide Japanese mCRPC PARP inhibitor TALAPRO‐2 talazoparib |
| url | https://doi.org/10.1002/cam4.70333 |
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