奥拉帕利治疗转移性去势抵抗性前列腺癌患者的耐受性和常见不良事件管理：来自 PROfound 研究的进一步分析。

Olaparib tolerability and common adverse-event management in patients with metastatic castration-resistant prostate cancer: Further analyses from the PROfound study.

机构信息

Department of Medical Oncology, Institut Bergonié, Bordeaux, France.

Department of Internal Medicine, Division of Medical Oncology, Cerrahpaşa School of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkey.

出版信息

Eur J Cancer. 2022 Jul;170:73-84. doi: 10.1016/j.ejca.2022.04.016. Epub 2022 May 19.

BACKGROUND

Based on PROfound, olaparib is approved for patients with metastatic castration-resistant prostate cancer following disease progression on at least enzalutamide or abiraterone and who carry relevant alterations in DNA repair genes. To facilitate continued olaparib treatment as long as the patient derives benefit, we describe further safety assessments from PROfound focusing on the four most common adverse events (AEs) and events of special interest.

METHODS

Patients were randomized (2:1) to olaparib tablets (300 mg bid) or control (enzalutamide or abiraterone) until disease progression or unacceptable toxicity. Safety was assessed through AE reporting and laboratory assessments. Safety data were also collected from all patients in the control group who experienced radiographic disease progression and subsequently crossed over to olaparib treatment.

RESULTS

256 patients received olaparib and 130 control. Incidence rates for the four most commonly occurring AEs in the olaparib group (all-causality) were anaemia 50%, nausea 43%, fatigue/asthenia 42% and decreased appetite 31%. All were mostly Grade 1 and 2 and all peaked within the first 2 months of treatment as the events were managed where appropriate, primarily with dose interruptions or dose reductions. The extent of bone metastases at baseline or prior taxane use was not associated with the rate of anaemia. Pneumonitis was reported in 2% and 1.5% of patients in the olaparib and control groups, respectively, and one patient (0.4%) in the olaparib group experienced an event of MDS/AML after a 30-day follow-up period. Venous thromboembolic events occurred in 8% of olaparib and 3% of control patients.

CONCLUSIONS

The four most common AEs observed in PROfound were generally manageable without the need for treatment discontinuation, allowing patients to remain on treatment for as long as they were deriving clinical benefit.

CLINICALTRIALS

gov registration number: NCT02987543.

背景

基于 PROfound 研究，奥拉帕利获批用于至少接受过恩扎卢胺或阿比特龙治疗后疾病进展且携带相关 DNA 修复基因改变的转移性去势抵抗性前列腺癌患者。为了只要患者受益就继续使用奥拉帕利治疗，我们进一步描述了 PROfound 研究的安全性评估结果，重点关注了 4 种最常见的不良事件（AE）和特殊关注的事件。

方法

患者按 2:1 随机分组，分别接受奥拉帕利片剂（300mg，每日两次）或对照（恩扎卢胺或阿比特龙）治疗，直至疾病进展或出现不可接受的毒性。安全性通过 AE 报告和实验室评估进行评估。也从所有在对照治疗中经历影像学疾病进展后交叉至奥拉帕利治疗的患者中收集了安全性数据。

结果

256 例患者接受了奥拉帕利治疗，130 例患者接受了对照治疗。奥拉帕利组（全因）最常发生的 4 种 AE 的发生率分别为贫血 50%、恶心 43%、乏力/虚弱 42%和食欲下降 31%。所有 AE 均主要为 1 级和 2 级，且均在治疗的前 2 个月内达到峰值，通过适当的剂量中断或剂量减少对 AE 进行了管理。基线时或之前使用紫杉烷治疗时的骨转移程度与贫血发生率无关。奥拉帕利组和对照组的肺炎发生率分别为 2%和 1.5%，奥拉帕利组有 1 例（0.4%）患者在 30 天随访期间发生 MDS/AML 事件。奥拉帕利组和对照组的静脉血栓栓塞事件发生率分别为 8%和 3%。