Background

Talazoparib has shown antitumor activity with a manageable safety profile in men with metastatic castration-resistant prostate cancer (mCRPC) and DNA damage response (DDR)/homologous recombination repair (HRR) alterations.

Objective

To evaluate patient-reported health-related quality of life (HRQoL) and pain in patients who received talazoparib in the TALAPRO-1 study, with a special interest in patients harboring breast cancer susceptibility gene 1 or 2 (BRCA1/2) mutations.

Design, setting, and participants

TALAPRO-1 is a single-arm, phase 2 study in men with mCRPC DDR alterations either directly or indirectly involved in HRR, who previously received one to two taxane-based chemotherapy regimens for advanced prostate cancer and whose mCRPC progressed on one or more novel hormonal agents.

Outcome measurements and statistical analysis

Men completed the European Quality-of-life Five-dimension Five-level scale (EQ-5D-5L), EQ-5D visual analog scale (VAS), and Brief Pain Inventory—Short Form at predefined time points during the study. The patient-reported outcome (PRO) population included men who completed a baseline and one or more postbaseline assessments before study end. Longitudinal mixed-effect models assuming an unstructured covariance matrix were used to estimate the mean (95% confidence interval [CI]) change from baseline for pain and general health status measurements among all patients and patients with BRCA1/2 mutations.

Results and limitations

In the 97 men in the PRO population treated with talazoparib (BRCA1/2, n = 56), the mean (95% CI) EQ-5D-5L Index improved (all patients, 0.05 [0.01, 0.08]; BRCA1/2 subset, 0.07 [0.03, 0.10]), as did the EQ-5D VAS scores (all patients, 5.42 [2.65, 8.18]; BRCA1/2 subset, 4.74 [1.07, 8.41]). Improvements in the estimated overall change from baseline (95% CI) in the mean worst pain were observed in all patients (–1.08 [–1.52, –0.65]) and the BRCA1/2 subset (–1.15 [–1.67, –0.62]). The probability of not having had experienced deterioration of worst pain by month 12 was 84% for all patients and 83% for the BRCA1/2 subset.

Conclusions

In heavily pretreated men with mCRPC and DDR/HRR alterations, talazoparib was associated with improved HRQoL in all patients and the BRCA1/2 subset. In both patient groups, worst pain improved from baseline and the probability of not experiencing a deterioration in worst pain with talazoparib was high.

Patient summary

We show that talazoparib was associated at least with no change or improvements in health-related quality of life (HRQoL) and pain burden in men with metastatic castration-resistant prostate cancer and DNA damage response/homologous recombination repair gene alterations in the TALAPRO-1 study. These findings in patient-reported HRQoL and pain complement the antitumor activity and tolerability profile of talazoparib.

中文翻译：

---

接受 Talazoparib 治疗的具有 DNA 损伤反应改变的转移性去势抵抗性前列腺癌患者的患者报告结果：来自 TALAPRO-1 的结果

背景

Talazoparib 在患有转移性去势抵抗性前列腺癌 (mCRPC) 和 DNA 损伤反应 (DDR)/同源重组修复 (HRR) 改变的男性中显示出抗肿瘤活性和可控的安全性。

客观的

评估在 TALAPRO-1 研究中接受他拉唑帕尼治疗的患者报告的健康相关生活质量 (HRQoL) 和疼痛，特别关注携带乳腺癌易感基因 1 或 2 (BRCA1/2) 突变的患者。

设计、设置和参与者

TALAPRO-1 是一项针对直接或间接参与 HRR 的 mCRPC DDR 改变的男性的单组 2 期研究，这些男性之前接受过一到两种基于紫杉烷类的晚期前列腺癌化疗方案，并且其 mCRPC 在一种或多种新药上进展荷尔蒙剂。

结果测量和统计分析

在研究期间的预定时间点，男性完成了欧洲生活质量五维五级量表 (EQ-5D-5L)、EQ-5D 视觉模拟量表 (VAS) 和简要疼痛量表 - 简短表格。患者报告结果 (PRO) 人群包括在研究结束前完成基线和一项或多项基线后评估的男性。使用假设非结构化协方差矩阵的纵向混合效应模型来估计所有患者和BRCA1/2突变患者的疼痛和一般健康状况测量值相对于基线的平均变化（95% 置信区间 [CI]）。

结果和局限性

在接受他拉唑帕尼治疗的 PRO 人群中的 97 名男性中（BRCA1/2，n  = 56），平均（95% CI）EQ-5D-5L 指数得到改善（所有患者，0.05 [0.01, 0.08]；BRCA1/2子集, 0.07 [0.03, 0.10])，EQ-5D VAS 评分也是如此（所有患者，5.42 [2.65, 8.18]；BRCA1/2子集，4.74 [1.07, 8.41]）。在所有患者 (–1.08 [–1.52, –0.65]) 和BRCA1/2子集 (–1.15 [–1.67, –0.62] ) 中观察到平均最严重疼痛相对于基线的估计总体变化 (95% CI) 有所改善). 到第 12 个月没有经历过最严重疼痛恶化的概率对于所有患者为 84%，对于BRCA1/2子集为 83%。

结论

在患有 mCRPC 和 DDR/HRR 改变的大量预处理男性中，talazoparib 与所有患者和BRCA1/2子集的 HRQoL 改善相关。在这两个患者组中，最严重的疼痛都比基线有所改善，并且使用他拉唑帕利后最严重的疼痛没有恶化的可能性很高。

患者总结

我们表明，talazoparib 至少与转移性去势抵抗性前列腺癌男性的健康相关生活质量 (HRQoL) 和疼痛负担没有变化或改善相关，并且 TALAPRO-1 中的 DNA 损伤反应/同源重组修复基因改变学习。这些在患者报告的 HRQoL 和疼痛方面的发现补充了他拉唑帕尼的抗肿瘤活性和耐受性特征。