Arun A. Azad , Karim Fizazi , Nobuaki Matsubara , Fred Saad , Ugo De Giorgi , Jae Young Joung , Peter C.C. Fong , Robert J. Jones , Stefanie Zschäbitz , Jan Oldenburg , Neal D. Shore , Curtis Dunshee , Joan Carles , Andre P. Fay , Xun Lin , Liza DeAnnuntis , Nicola Di Santo , Michael A. Zielinski , Neeraj Agarwal
{"title":"他唑帕利联合恩杂鲁胺治疗转移性耐受性前列腺癌：随机、安慰剂对照、III 期 TALAPRO-2 研究的安全性分析","authors":"Arun A. Azad , Karim Fizazi , Nobuaki Matsubara , Fred Saad , Ugo De Giorgi , Jae Young Joung , Peter C.C. Fong , Robert J. Jones , Stefanie Zschäbitz , Jan Oldenburg , Neal D. Shore , Curtis Dunshee , Joan Carles , Andre P. Fay , Xun Lin , Liza DeAnnuntis , Nicola Di Santo , Michael A. Zielinski , Neeraj Agarwal","doi":"10.1016/j.ejca.2024.115078","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>This detailed analysis further characterizes the safety profile of talazoparib plus enzalutamide in the ongoing randomized, phase III TALAPRO-2 study in patients with metastatic castration-resistant prostate cancer (mCRPC). In both the all-comers and homologous recombination repair (HRR)-deficient populations, talazoparib plus enzalutamide significantly improved radiographic progression-free survival compared with placebo plus enzalutamide.</div></div><div><h3>Methods</h3><div>The talazoparib plus enzalutamide safety populations in TALAPRO-2 included 398 patients from cohort 1 (all-comers, unselected for HRR gene alterations) and 198 patients from the combined HRR-deficient population (patients from the all-comers population with HRR gene alterations plus subsequently enrolled patients with HRR gene alterations; cohort 2). Patients received talazoparib 0.5 mg (0.35 mg, moderate renal impairment) and enzalutamide 160 mg once daily. Safety analyses evaluated common treatment-emergent adverse events (TEAE), their type, severity, timing, seriousness, and relationship to study treatment.</div></div><div><h3>Results</h3><div>In the all-comers (n = 398) and HRR-deficient populations (n = 198), all-cause grade 3/4 (G3/4) TEAEs with talazoparib plus enzalutamide were reported in 71.9 % and 66.2 % of patients, respectively. Most common G3/4 hematologic TEAEs were anemia (46.7 % and 40.9 %, respectively), neutropenia (18.3 % and 18.7 %), and thrombocytopenia (7.3 % and 7.1 %). Median time to event was 3.3 and 3.3 months for G3/4 anemia, 2.3 and 2.3 months for G3/4 neutropenia, and 2.3 and 1.5 months for G3/4 thrombocytopenia. Maximum hemoglobin reduction occurred after 13 and 15 weeks of treatment. 18.8 % and 10.1 % of patients discontinued talazoparib. TEAEs were managed with dose interruption (62.1 % and 57.6 %), reduction (52.8 % and 52.0 %), hematologic supportive care (13.1 % and 10.6 %), and packed red blood cell transfusions (39.2 % and 35.9 %).</div></div><div><h3>Conclusion</h3><div>Talazoparib plus enzalutamide had a generally manageable safety profile in patients with mCRPC within the all-comers and the HRR-deficient populations.</div></div><div><h3>ClinicalTrials.gov Identifier</h3><div>NCT03395197</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"213 ","pages":"Article 115078"},"PeriodicalIF":7.6000,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Talazoparib plus enzalutamide in metastatic castration-resistant prostate cancer: Safety analyses from the randomized, placebo-controlled, phase III TALAPRO-2 study\",\"authors\":\"Arun A. Azad , Karim Fizazi , Nobuaki Matsubara , Fred Saad , Ugo De Giorgi , Jae Young Joung , Peter C.C. Fong , Robert J. Jones , Stefanie Zschäbitz , Jan Oldenburg , Neal D. Shore , Curtis Dunshee , Joan Carles , Andre P. Fay , Xun Lin , Liza DeAnnuntis , Nicola Di Santo , Michael A. Zielinski , Neeraj Agarwal\",\"doi\":\"10.1016/j.ejca.2024.115078\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>This detailed analysis further characterizes the safety profile of talazoparib plus enzalutamide in the ongoing randomized, phase III TALAPRO-2 study in patients with metastatic castration-resistant prostate cancer (mCRPC). In both the all-comers and homologous recombination repair (HRR)-deficient populations, talazoparib plus enzalutamide significantly improved radiographic progression-free survival compared with placebo plus enzalutamide.</div></div><div><h3>Methods</h3><div>The talazoparib plus enzalutamide safety populations in TALAPRO-2 included 398 patients from cohort 1 (all-comers, unselected for HRR gene alterations) and 198 patients from the combined HRR-deficient population (patients from the all-comers population with HRR gene alterations plus subsequently enrolled patients with HRR gene alterations; cohort 2). Patients received talazoparib 0.5 mg (0.35 mg, moderate renal impairment) and enzalutamide 160 mg once daily. Safety analyses evaluated common treatment-emergent adverse events (TEAE), their type, severity, timing, seriousness, and relationship to study treatment.</div></div><div><h3>Results</h3><div>In the all-comers (n = 398) and HRR-deficient populations (n = 198), all-cause grade 3/4 (G3/4) TEAEs with talazoparib plus enzalutamide were reported in 71.9 % and 66.2 % of patients, respectively. Most common G3/4 hematologic TEAEs were anemia (46.7 % and 40.9 %, respectively), neutropenia (18.3 % and 18.7 %), and thrombocytopenia (7.3 % and 7.1 %). Median time to event was 3.3 and 3.3 months for G3/4 anemia, 2.3 and 2.3 months for G3/4 neutropenia, and 2.3 and 1.5 months for G3/4 thrombocytopenia. Maximum hemoglobin reduction occurred after 13 and 15 weeks of treatment. 18.8 % and 10.1 % of patients discontinued talazoparib. TEAEs were managed with dose interruption (62.1 % and 57.6 %), reduction (52.8 % and 52.0 %), hematologic supportive care (13.1 % and 10.6 %), and packed red blood cell transfusions (39.2 % and 35.9 %).</div></div><div><h3>Conclusion</h3><div>Talazoparib plus enzalutamide had a generally manageable safety profile in patients with mCRPC within the all-comers and the HRR-deficient populations.</div></div><div><h3>ClinicalTrials.gov Identifier</h3><div>NCT03395197</div></div>\",\"PeriodicalId\":11980,\"journal\":{\"name\":\"European Journal of Cancer\",\"volume\":\"213 \",\"pages\":\"Article 115078\"},\"PeriodicalIF\":7.6000,\"publicationDate\":\"2024-10-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0959804924012097\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Cancer","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0959804924012097","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Talazoparib plus enzalutamide in metastatic castration-resistant prostate cancer: Safety analyses from the randomized, placebo-controlled, phase III TALAPRO-2 study
Background
This detailed analysis further characterizes the safety profile of talazoparib plus enzalutamide in the ongoing randomized, phase III TALAPRO-2 study in patients with metastatic castration-resistant prostate cancer (mCRPC). In both the all-comers and homologous recombination repair (HRR)-deficient populations, talazoparib plus enzalutamide significantly improved radiographic progression-free survival compared with placebo plus enzalutamide.
Methods
The talazoparib plus enzalutamide safety populations in TALAPRO-2 included 398 patients from cohort 1 (all-comers, unselected for HRR gene alterations) and 198 patients from the combined HRR-deficient population (patients from the all-comers population with HRR gene alterations plus subsequently enrolled patients with HRR gene alterations; cohort 2). Patients received talazoparib 0.5 mg (0.35 mg, moderate renal impairment) and enzalutamide 160 mg once daily. Safety analyses evaluated common treatment-emergent adverse events (TEAE), their type, severity, timing, seriousness, and relationship to study treatment.
Results
In the all-comers (n = 398) and HRR-deficient populations (n = 198), all-cause grade 3/4 (G3/4) TEAEs with talazoparib plus enzalutamide were reported in 71.9 % and 66.2 % of patients, respectively. Most common G3/4 hematologic TEAEs were anemia (46.7 % and 40.9 %, respectively), neutropenia (18.3 % and 18.7 %), and thrombocytopenia (7.3 % and 7.1 %). Median time to event was 3.3 and 3.3 months for G3/4 anemia, 2.3 and 2.3 months for G3/4 neutropenia, and 2.3 and 1.5 months for G3/4 thrombocytopenia. Maximum hemoglobin reduction occurred after 13 and 15 weeks of treatment. 18.8 % and 10.1 % of patients discontinued talazoparib. TEAEs were managed with dose interruption (62.1 % and 57.6 %), reduction (52.8 % and 52.0 %), hematologic supportive care (13.1 % and 10.6 %), and packed red blood cell transfusions (39.2 % and 35.9 %).
Conclusion
Talazoparib plus enzalutamide had a generally manageable safety profile in patients with mCRPC within the all-comers and the HRR-deficient populations.
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