利用时间不佳的G-Rate方法评估带有前列腺转移性癌症的美国退伍军人的Olaparib疗效，非常适合现实世界分析

我们的目的是通过利用国家数据存储库来评估与转移性前列腺癌（MPC）的美国退伍军人（MPC）评估PARP抑制剂Olaparib的现实疗效（HRR），2）接受Olaparib单药治疗以及一种新型的激素治疗/雄激素受体途径抑制剂（NHT/ARPI）和/或化学疗法，以及3）在接受治疗时使用PSA值的可估计的肿瘤生长速率（G-RATE）。先前的工作表明，G型与生存的极好相关性。使用G-Rate，我们确定肿瘤加倍时间（DT）和DT比（olaparib/dt的DT在先前的药物上）。我们假设DT比≥1与福利有关。我们确定了139名退伍军人，其中包括42名肿瘤的黑人雄性，其中携带了HRR基因的突变/改变Olaparib：BRCA2（50），ATM（32），BRCA1（32），BRCA1（10），其他突变（47）。 62/139（45％）和黑人退伍军人的21/42（50％）的DT比≥1，包括31、10、2和19，分别为BRCA2，ATM，BRCA1和其他突变（P = 0.006）。 DT比≥1的中位生存期优点，DT比<1比11.4个月（P = 0.01，HR 0.50，95％CI 0.29-0.85）。未观察到olaparib的生殖线状态，启动PSA值，先前疗法数量或立即先前治疗的olaparib受益于DT比≥1。 Compared to matched cohorts, tumors in the olaparib cohort had shorter DTs with enzalutamide in first line (367 vs. 884 days; p = 0.0043).Using equations indifferent to timing of assessments ideal for real-world efficacy analyses, we showed DT ratio ≥1 representing slower tumor growth on olaparib relative to the prior therapy correlates with improved survival. MPC携带突变/HRR基因改变的退伍军人的Olaparib疗效模仿了临床试验结果。黑人的结果可比。与匹配的队列相比，在第一线中，恩扎拉他胺在HRR基因中具有突变/改变的肿瘤中不太有效。美国临床肿瘤学会征服癌症基金会（ASCO CCF），Blavatnik家庭基金会和前列腺癌基金会（PCF）（PCF）。

We aimed to assess real-world efficacy of the PARP inhibitor, olaparib, in US Veterans with metastatic prostate cancer (mPC) by leveraging the national data repository and evaluate a novel approach to assess treatment efficacy in tumors considered rare or harboring rare mutations.Included Veterans had 1) mPC with somatic or germline alterations/mutations in genes involved in homologous recombination repair (HRR), 2) received olaparib monotherapy as well as a novel hormonal therapy/androgen receptor pathway inhibitors (NHT/ARPI), and/or chemotherapy, and 3) estimable rates of tumor growth (g-rate) using PSA values obtained while receiving treatment. Previous work has shown an excellent inverse correlation of g-rate with survival. Using g-rate, we determined tumor doubling time (DT) and DT ratios (DT on olaparib/DT on prior medication). We postulated that a DT ratio≥ 1 was associated with benefit.We identified 139 Veterans, including 42 Black males with tumors harboring mutations/alterations in HRR genes who received olaparib: BRCA2 (50), ATM (32), BRCA1 (10), other mutations (47). 62/139 (45%) of all and 21/42 (50%) of Black Veterans had DT ratios ≥1, including 31, 10, 2, and 19 with BRCA2, ATM, BRCA1, and other mutations, respectively (p = 0.006). Median survival with DT ratios ≥1 was superior, being 24.5 vs. 11.4 months for DT ratio <1 (p = 0.01, HR 0.50, 95% CI 0.29-0.85). Benefit from olaparib, defined as DT ratio ≥1, was not observed for germline status, starting PSA value, number of prior therapies, or immediate prior therapy. Compared to matched cohorts, tumors in the olaparib cohort had shorter DTs with enzalutamide in first line (367 vs. 884 days; p = 0.0043).Using equations indifferent to timing of assessments ideal for real-world efficacy analyses, we showed DT ratio ≥1 representing slower tumor growth on olaparib relative to the prior therapy correlates with improved survival. Olaparib efficacy in Veterans with mPC harboring mutations/alterations in HRR genes emulates clinical trial results. Black men had comparable results. Compared to matched cohorts, in first line, enzalutamide was less efficacious in tumors harboring mutations/alterations in HRR genes.American Society of Clinical Oncology Conquer Cancer Foundation (ASCO CCF), the Blavatnik Family Foundation and the Prostate Cancer Foundation (PCF).