在同源重组修复基因中存在致病性改变的前列腺癌患者的 DNA 损伤治疗。
DNA-Damaging Therapies in Patients With Prostate Cancer and Pathogenic Alterations in Homologous Recombination Repair Genes.
机构信息
University of Colorado, Aurora, CO.
University of Michigan, Ann Arbor, MI.
出版信息
JCO Precis Oncol. 2024 Aug;8:e2400014. doi: 10.1200/PO.24.00014.
PURPOSE
Outcomes data for DNA-damaging therapeutics for men with prostate cancer (PC) and non- homologous recombination repair (HRR) mutations are limited. We evaluated outcomes by HRR alteration in men with PC treated with poly(ADP-ribose)polymerase inhibitors (PARPi) and/or platinum chemotherapy.
METHODS
Retrospective data from the PROMISE consortium were used. Clinical outcomes differences were assessed between patients with / mutations (cohort A) and those with HRR mutations without direct BRCA complex interaction (cohort B: , , , , and ). Outcomes in patients with HRR mutations with direct BRCA complex interaction were also explored (cohort C: , , , , , , and ).
RESULTS
One hundred and forty-six patients received PARPi (cohort A: 94, cohort B: 45, cohort C: 7) and 104 received platinum chemotherapy (cohort A: 48, cohort B: 44, cohort C: 10). PSA50 response rate to PARPi was higher in cohort A (61%) than cohort B (5%), < .001. Median clinical/radiographic progression-free survival (crPFS) with PARPi in cohort A was significantly longer than in cohort B: 15.9 versus 8.7 months, = .005. PSA50 response rate to platinum therapy was higher in cohort A (62%) than in cohort B (32%), = .024, although crPFS was not significantly different. PSA50 response rate to PARPi and platinum was 40% and 32%, respectively, in cohort C. In multivariable analysis, cohort A had significantly improved overall survival and crPFS compared with cohort B with PARPi but not platinum chemotherapy.
CONCLUSION
Patients with -mutated PC had significantly improved outcomes to PARPi but not platinum chemotherapy compared with those with HRR mutations without direct BRCA complex interaction.
目的
针对携带前列腺癌（PC）和非同源重组修复（HRR）突变的男性使用 DNA 损伤治疗药物的结局数据有限。我们评估了接受聚（ADP-核糖）聚合酶抑制剂（PARPi）和/或铂类化疗的 PC 男性中 HRR 改变的结局。
方法
使用 PROMISE 联盟的回顾性数据。评估了具有 / 突变的患者（队列 A）与 HRR 突变但无直接 BRCA 复合物相互作用的患者（队列 B： 、 、 、 、 ）之间的临床结局差异。还探讨了具有直接 BRCA 复合物相互作用的 HRR 突变患者的结局（队列 C： 、 、 、 、 、 ）。
结果
146 例患者接受 PARPi（队列 A：94 例，队列 B：45 例，队列 C：7 例），104 例患者接受铂类化疗（队列 A：48 例，队列 B：44 例，队列 C：10 例）。PARPi 治疗后 PSA50 缓解率在队列 A（61%）中高于队列 B（5%）， ＜0.001。队列 A 中 PARPi 治疗的中位临床/影像学无进展生存期（crPFS）明显长于队列 B：15.9 个月对 8.7 个月， =0.005。队列 A 中铂类治疗的 PSA50 缓解率高于队列 B（62%对 32%）， =0.024，尽管 crPFS 无显著差异。队列 C 中 PARPi 和铂类的 PSA50 缓解率分别为 40%和 32%。多变量分析显示，与 HRR 突变但无直接 BRCA 复合物相互作用的患者相比，接受 PARPi 治疗的队列 A 的总生存和 crPFS 显著改善，而接受铂类化疗的患者则无显著改善。
结论
与 HRR 突变但无直接 BRCA 复合物相互作用的患者相比，携带 - 突变的 PC 患者接受 PARPi 治疗的结局显著改善，但接受铂类化疗的结局则无显著改善。
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