Mike Wenzel, Florestan Koll, Benedikt Hoeh, Clara Humke, Henning Reis, Peter Wild, Thomas Steuber, Markus Graefen, Derya Tilki, Amir Sabet, Daniel Gröner, Felix K H Chun, Philipp Mandel
{"title":"具有BRCA基因或肿瘤抑制基因突变的转移性去势抵抗性前列腺癌患者接受177-前列腺特异性膜抗原放射配体治疗的癌症控制结果","authors":"Mike Wenzel, Florestan Koll, Benedikt Hoeh, Clara Humke, Henning Reis, Peter Wild, Thomas Steuber, Markus Graefen, Derya Tilki, Amir Sabet, Daniel Gröner, Felix K H Chun, Philipp Mandel","doi":"10.1200/PO-24-00645","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Several tumor gene mutations are known for metastatic castration-resistant prostate cancer (mCRPC). The individual response to 177-lutetium prostate specific membrane antigen radioligand therapy (Lu-PSMA) is under current investigation regarding the genomic profile of patients with mCRPC.</p><p><strong>Materials and methods: </strong>We relied on the FRAMCAP database and compared progression-free survival (PFS) and overall survival (OS) rates of patients with mCRPC with breast cancer-related antigen (<i>BRCA</i>) or tumor suppressor gene mutations (<i>TP53</i>, <i>PTEN</i>, <i>RB1</i>). Specifically, subgroup analyses were performed for patients with Lu-PSMA-treated mCRPC.</p><p><strong>Results: </strong>Of 194 patients with mCRPC, 22% was <i>BRCA1/2</i> versus 14% <i>PTEN/TP53/RB1</i> versus 63% without one of these mutations. Patients with no mutation harbored a significantly lower Gleason score of 8-10, relative to <i>BRCA</i> and <i>PTEN/TP53/RB1</i> patients. In PFS analyses of first-line mCRPC, no difference between all three groups was observed, whereas the median OS differed significantly with 46.3 versus 48.7 versus 95.4 months for <i>BRCA</i> versus <i>PTEN/TP53/RB1</i> versus no mutated patients (<i>P</i> < .05). In univariable Cox regression models, BRCA-mutated patients were at higher risk of death (hazard ratio, 2.57; <i>P</i> < .01), whereas <i>PTEN/TP53/RB1</i> patients were not (<i>P</i> = .4). Of 87 patients with Lu-PSMA-treated mCRPC, significant differences in PFS and OS were observed (both <i>P</i> ≤ .02). In univariable and multivariable Cox regression models, BRCA-mutated Lu-PSMA patients were at higher risk of death, whereas <i>PTEN/TP53/RB1</i> patients had similar outcomes as no mutated patients.</p><p><strong>Conclusion: </strong>In real-world setting, substantially lower OS in mCRPC is observed for <i>BRCA</i>- and <i>PTEN/TP53/RB1</i>-mutated patients, whereas no difference in first-line PFS could be computed. In Lu-PSMA-treated patients, worst outcomes were observed for <i>BRCA</i> patients.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400645"},"PeriodicalIF":5.3000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cancer-Control Outcomes of Patients With Metastatic Castration-Resistant Prostate Cancer With <i>BRCA</i> Gene or Tumor Suppressor Mutations Undergoing 177-Lutetium Prostate-Specific Membrane Antigen Radioligand Therapy.\",\"authors\":\"Mike Wenzel, Florestan Koll, Benedikt Hoeh, Clara Humke, Henning Reis, Peter Wild, Thomas Steuber, Markus Graefen, Derya Tilki, Amir Sabet, Daniel Gröner, Felix K H Chun, Philipp Mandel\",\"doi\":\"10.1200/PO-24-00645\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Several tumor gene mutations are known for metastatic castration-resistant prostate cancer (mCRPC). The individual response to 177-lutetium prostate specific membrane antigen radioligand therapy (Lu-PSMA) is under current investigation regarding the genomic profile of patients with mCRPC.</p><p><strong>Materials and methods: </strong>We relied on the FRAMCAP database and compared progression-free survival (PFS) and overall survival (OS) rates of patients with mCRPC with breast cancer-related antigen (<i>BRCA</i>) or tumor suppressor gene mutations (<i>TP53</i>, <i>PTEN</i>, <i>RB1</i>). Specifically, subgroup analyses were performed for patients with Lu-PSMA-treated mCRPC.</p><p><strong>Results: </strong>Of 194 patients with mCRPC, 22% was <i>BRCA1/2</i> versus 14% <i>PTEN/TP53/RB1</i> versus 63% without one of these mutations. Patients with no mutation harbored a significantly lower Gleason score of 8-10, relative to <i>BRCA</i> and <i>PTEN/TP53/RB1</i> patients. In PFS analyses of first-line mCRPC, no difference between all three groups was observed, whereas the median OS differed significantly with 46.3 versus 48.7 versus 95.4 months for <i>BRCA</i> versus <i>PTEN/TP53/RB1</i> versus no mutated patients (<i>P</i> < .05). In univariable Cox regression models, BRCA-mutated patients were at higher risk of death (hazard ratio, 2.57; <i>P</i> < .01), whereas <i>PTEN/TP53/RB1</i> patients were not (<i>P</i> = .4). Of 87 patients with Lu-PSMA-treated mCRPC, significant differences in PFS and OS were observed (both <i>P</i> ≤ .02). In univariable and multivariable Cox regression models, BRCA-mutated Lu-PSMA patients were at higher risk of death, whereas <i>PTEN/TP53/RB1</i> patients had similar outcomes as no mutated patients.</p><p><strong>Conclusion: </strong>In real-world setting, substantially lower OS in mCRPC is observed for <i>BRCA</i>- and <i>PTEN/TP53/RB1</i>-mutated patients, whereas no difference in first-line PFS could be computed. In Lu-PSMA-treated patients, worst outcomes were observed for <i>BRCA</i> patients.</p>\",\"PeriodicalId\":14797,\"journal\":{\"name\":\"JCO precision oncology\",\"volume\":\"8 \",\"pages\":\"e2400645\"},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JCO precision oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1200/PO-24-00645\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/12/6 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JCO precision oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1200/PO-24-00645","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/6 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Cancer-Control Outcomes of Patients With Metastatic Castration-Resistant Prostate Cancer With BRCA Gene or Tumor Suppressor Mutations Undergoing 177-Lutetium Prostate-Specific Membrane Antigen Radioligand Therapy.
Purpose: Several tumor gene mutations are known for metastatic castration-resistant prostate cancer (mCRPC). The individual response to 177-lutetium prostate specific membrane antigen radioligand therapy (Lu-PSMA) is under current investigation regarding the genomic profile of patients with mCRPC.
Materials and methods: We relied on the FRAMCAP database and compared progression-free survival (PFS) and overall survival (OS) rates of patients with mCRPC with breast cancer-related antigen (BRCA) or tumor suppressor gene mutations (TP53, PTEN, RB1). Specifically, subgroup analyses were performed for patients with Lu-PSMA-treated mCRPC.
Results: Of 194 patients with mCRPC, 22% was BRCA1/2 versus 14% PTEN/TP53/RB1 versus 63% without one of these mutations. Patients with no mutation harbored a significantly lower Gleason score of 8-10, relative to BRCA and PTEN/TP53/RB1 patients. In PFS analyses of first-line mCRPC, no difference between all three groups was observed, whereas the median OS differed significantly with 46.3 versus 48.7 versus 95.4 months for BRCA versus PTEN/TP53/RB1 versus no mutated patients (P < .05). In univariable Cox regression models, BRCA-mutated patients were at higher risk of death (hazard ratio, 2.57; P < .01), whereas PTEN/TP53/RB1 patients were not (P = .4). Of 87 patients with Lu-PSMA-treated mCRPC, significant differences in PFS and OS were observed (both P ≤ .02). In univariable and multivariable Cox regression models, BRCA-mutated Lu-PSMA patients were at higher risk of death, whereas PTEN/TP53/RB1 patients had similar outcomes as no mutated patients.
Conclusion: In real-world setting, substantially lower OS in mCRPC is observed for BRCA- and PTEN/TP53/RB1-mutated patients, whereas no difference in first-line PFS could be computed. In Lu-PSMA-treated patients, worst outcomes were observed for BRCA patients.
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