奥拉帕利治疗同源重组修复基因改变的 mCRPC 患者：PROfound 亚洲亚组分析。
Olaparib in patients with mCRPC with homologous recombination repair gene alterations: PROfound Asian subset analysis.
机构信息
National Cancer Center Hospital East, Chiba, Japan.
Osaka International Cancer Institute, Osaka, Japan.
出版信息
Jpn J Clin Oncol. 2022 May 5;52(5):441-448. doi: 10.1093/jjco/hyac015.
BACKGROUND
The Phase III PROfound study (NCT02987543) evaluated olaparib versus abiraterone or enzalutamide (control; randomized 2:1 to olaparib or control) in men with homologous recombination repair gene alterations and metastatic castration-resistant prostate cancer whose disease progressed on prior next-generation hormonal agent.
METHODS
We present efficacy and safety data from an exploratory post hoc analysis of olaparib in the PROfound Asian subset. Analyses were not planned, alpha controlled or powered. Of 101 Asian patients enrolled in Japan (n=57), South Korea (n=29) and Taiwan (n=15), 66 and 35 patients received olaparib and control, respectively.
RESULTS
Radiographic progression-free survival (rPFS) and overall survival (OS) favored olaparib versus control in Cohort A [rPFS 7.2 vs. 4.5 months, HR 0.58, 95% CI 0.29-1.21, P = 0.14 (nominal); OS 23.4 vs. 17.8 months, HR 0.81, 95% CI 0.40-1.74, P = 0.57 (nominal)] and Cohorts A+B [rPFS 5.8 vs. 3.5 months, HR 0.69, 95% CI 0.42-1.16, P = 0.13 (nominal); OS 18.6 vs. 16.2 months, HR 0.96, 95% CI 0.56-1.70, P = 0.9 (nominal)]. Olaparib showed greatest improvement in patients harboring BRCA alterations [rPFS 9.3 vs. 3.5 months, HR 0.17, 95% CI 0.06-0.49, P = 0.0003 (nominal); OS 26.8 vs. 14.3 months, HR 0.62, 95% CI 0.24-1.79, P = 0.34 (nominal)]. Safety data were consistent with the known profile of olaparib, with no new safety signals identified.
CONCLUSION
In PROfound, there was a statistically significant improvement in outcomes reported in the global population of patients with metastatic castration-resistant prostate cancer and alterations in homologous recombination repair genes whose disease progressed on prior next-generation hormonal agent compared with control. For the subset of Asian patients reported here, exploratory analysis suggested that there was also an improvement in outcomes versus control. The safety and tolerability of olaparib in Asian patients were similar to that of the PROfound global population.
CLINICAL TRIAL NUMBER
ClinicalTrials.gov NCT02987543.
背景
III 期 PROfound 研究（NCT02987543）评估了奥拉帕利与阿比特龙或恩扎鲁胺（对照组；奥拉帕利与对照组按 2:1 随机分组）在先前接受下一代激素治疗后疾病进展的同源重组修复基因改变和转移性去势抵抗性前列腺癌男性患者中的疗效。
方法
我们报告了 PROfound 亚洲亚组中奥拉帕利的探索性事后分析的疗效和安全性数据。分析不是计划的，alpha 受控或加权。在日本（n=57）、韩国（n=29）和中国台湾（n=15）入组的 101 名亚洲患者中，分别有 66 名和 35 名患者接受了奥拉帕利和对照组治疗。
结果
在 Cohort A 中，与对照组相比，奥拉帕利在影像学无进展生存期（rPFS）和总生存期（OS）方面具有优势[rPFS 7.2 与 4.5 个月，HR 0.58，95%CI 0.29-1.21，P=0.14（名义值）；OS 23.4 与 17.8 个月，HR 0.81，95%CI 0.40-1.74，P=0.57（名义值）]和 Cohorts A+B[rPFS 5.8 与 3.5 个月，HR 0.69，95%CI 0.42-1.16，P=0.13（名义值）；OS 18.6 与 16.2 个月，HR 0.96，95%CI 0.56-1.70，P=0.9（名义值）]。奥拉帕利在携带 BRCA 改变的患者中显示出最大的改善[rPFS 9.3 与 3.5 个月，HR 0.17，95%CI 0.06-0.49，P=0.0003（名义值）；OS 26.8 与 14.3 个月，HR 0.62，95%CI 0.24-1.79，P=0.34（名义值）]。安全性数据与奥拉帕利已知的安全性特征一致，未发现新的安全性信号。
结论
在 PROfound 中，与对照组相比，先前接受下一代激素治疗后疾病进展的转移性去势抵抗性前列腺癌和同源重组修复基因改变的患者的全球人群报告的结局有统计学意义的改善。对于这里报告的亚洲患者亚组，探索性分析表明，与对照组相比，结局也有所改善。奥拉帕利在亚洲患者中的安全性和耐受性与 PROfound 全球人群相似。
临床试验编号
ClinicalTrials.gov NCT02987543。
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