编者按：“合成致死”的PARP抑制剂（PARPi）开启了前列腺癌精准治疗的序幕，其单药或联合新一代雄激素受体通路抑制剂（ARPI）的临床研究，如PROfound、PROpel等在转移性去势抵抗性前列腺癌（mCRPC）领域相继取得了具有里程碑意义的临床变革。BRCAAway研究进一步评估了PARPi联合APRI或PARPi、APRI单药不同一线治疗模式用于携带BRCA1/2或ATM突变mCRPC患者的疗效和安全性。在近日举行的2026年ASCO GU大会上，该研究公布的最新数据显示联合治疗组的中位OS长达68个月。《肿瘤瞭望》特邀中国香港养和医院潘明骏（Darren Poon）教授解读BRCAAway研究如下。

 

潘明骏（Darren Poon）教授：BRACAWAY研究是一项随机II期临床试验。这是一项由生物标志物驱动的研究，入组患者此前未接受过ARPI或PARP抑制剂、化疗治疗的mCRPC，且在胚系或体细胞检测中，携带BRCA1/2或ATM突变，并按1:1:1的比例随机分配到三个组中。前两个组是单独治疗组，分别是阿比特龙联合泼尼松，另一个单独治疗组是奥拉帕利。第三个组是奥拉帕利联合阿比特龙和泼尼松，旨在评估联合方案是否优于单独治疗方案。

 

 

这项研究的一个非常关键的特征是，在单独治疗组中，当患者病情进展时，研究允许他们交叉接受另一种尚未接受过的治疗。比如在阿比特龙治疗后出现进展的患者，可以交叉接受奥拉帕利治疗，反之亦然。此前该研究关于无进展生存期（PFS）的结果已经公布，联合治疗组相比于单药治疗方案具有非常出色的PFS。本次ASCO-GU大会更新的PFS依然保持PFS倾向于联合治疗组的显著获益，联合组、阿比特龙组、奥拉帕利组的中位PFS分别为39.0、14.0、8.6个月（Abi/pred＋Ola vs Abi/pred：HR 0.33；Abi/pred＋Ola vs Ola：HR 0.37）。

 

 

Oncology Frontier:In recent years，PARP inhibitors have accumulated a wealth of evidence-based medical data in the field of mCRPC，including the BRCAAway study.First，could you review the design characteristics of this study and the main findings previously reported?

 

Prof.Darren Poon:The BRACAWAY study is a randomized Phase II trial，which is a biomarker-driven study that evaluate patients with mCRPC disease without prior ARPI or PARP inhibitors.In the germline or somatic testing，they were found to have the BRCA1 or 2 or ATM mutations.So these patients has been enrolled and randomized into one-to-one-to-one fashion into three arms.The first two arms are the monotherapy with either abiraterone prednisone，and the other monotherapy arm is olaparib.And the third arm is olaparib plus abiraterone.So basically，there are three arms and try to evaluate whether the combination approach is the best versus the monotherapy approaches.And one of the very key characteristics of this study is in the monotherapy arms.While the patients have progressed，they could allow for crossover to the other treatments that they haven’t received.Like the patient，if they progress upon abiraterone，they could crossover to olaparib and vice-versa.So previously，the results of this study in regard to the progression-free survival has been released，showing that the combination arm has a very good PFS compared to the monotherapy approaches.

 

潘明骏（Darren Poon）教授：2026年的ASCO-GU大会报道了BRACAWAY研究的总生存期（OS）。我们可以看到奥拉帕利联合阿比特龙组中位OS最长，达到68个月；而阿比特龙组仅为28个月，奥拉帕利组则约为38个月。虽然这是一项随机II期临床试验，其初衷并非将OS数据作为主要终点来评估，但在该研究中明确显示，联合治疗组具有非常可观的中位OS，优于单独治疗方案。阿比特龙＋奥拉帕利联合组患者的死亡风险相较于阿比特龙组降低61%（68 vs 28个月，HR 0.39），相较于奥拉帕利组降低49%（68 vs 37个月，HR 0.49）。

 

 

Oncology Frontier:Following the positive PFS results，the OS outcomes of the BRCAAway study were reported at the ASCO-GU conference.Could you interpret the OS results of this study and their clinical significance?

 

Prof.Darren Poon:Yeah，in ASCO GU 2026，the overall survival data for the BRACAWAY trial has been released and presented.So we can see that the combination arm，that are olaparib plus abiraterone，has the longest median overall survival of up to 68 months，whereas for the monotherapy，such as abiraterone，only 28 months.And for olaparib，the median overall survival is around 38 months.So although this is a randomized Phase II trial and it doesn’t mean to assess the overall survival data as the primary endpoint，but in this study，it clearly showed that the combination arm has a very favorable median overall survival versus the monotherapy approaches.

 

潘明骏（Darren Poon）教授：我认为交叉设计是一个非常务实且具有实践意义的方法，反映了我们临床实践中的真实情况。出于对毒性、合并症或药物可及性的考虑，医生有时会选择使用单药治疗，无论是阿比特龙、奥拉帕利还是PARP抑制剂，随后再序贯使用其他疗法。我认为这是一个非常实用的方法。

 

在BRACAWAY试验中，确实显示出交叉使用其他药物的患者，例如从阿比特龙交叉到奥拉帕利，仍观察到了PSA缓解（奥拉帕利交叉组和阿比特龙交叉组的PSA缓解率分别为50%和63%），并且在后续治疗中也观察到了PFS的获益（两组中交叉治疗患者的中位PFS均可达16个月，而总体的阿比特龙组和奥拉帕利组的中位PFS分别为8.6个月和14.0个月），尽管最终的总体PFS或OS仍然劣于联合治疗组。因此，我认为这项研究告诉我们不同的方案可能有不同的治疗目标。对于联合治疗组，我认为其非常可观的最终OS、深度的PSA缓解以及更长的PFS是非常有利的，当然也会有毒性累加的考虑。而对于单药治疗，我认为对于那些担心毒性或有合并症等其他考虑的患者，我认为使用不同单药的序贯治疗方案也是一种非常合理的方案。

 

 

Oncology Frontier:The BRCAAway study allowed crossover between the two monotherapy arms，effectively representing a sequential monotherapy treatment model.Based on the crossover data，how do you view the treatment approaches involving PAPRi and NHT?

 

Prof.Darren Poon:I think the crossover design is a very pragmatic and practical approach and reflect the real-life settings in our clinical practice.Because of the consideration of the toxicities，comorbidities，or the access of the drugs，sometimes the physician will choose to use the monotherapy，either abiraterone or olaparib or PARP inhibitors，and then followed by the sequential use of the other therapies.And I think this is a very practical approach，and in this study，in the BRACAWAY trial，it did show that the patients who crossover to the other drugs，like abiraterone to olaparib，they still have a PSA response and the PFS is also observed with the subsequent therapies，despite the ultimate total PFS or overall survival is not...is still inferior to the combination arm.So therefore，I think this study informed us the different approaches may have a different goals of treatment.For the combination arm，I think the very favorable ultimate overall survival，a deep PSA response，a longer PFS is very favorable，and certainly there will be considerations of additive toxicities.But whereas for the monotherapies，I think for patients who are concerned of the toxicities or the other considerations like comorbidities，I think sequential approaches with different monotherapies is also a very reasonable approach.

 

潘明骏（Darren Poon）教授：我认为这三项重要的里程碑式研究，即PROpel、PROfound和BRACAWAY试验告知我们，基因检测在转移性前列腺癌的治疗模式中具有重要意义。在不同的治疗背景下，例如PROfound研究确立了PARP抑制剂对于ARPI和化疗经治mCRPC患者的治疗获益；PROpel研究确立了奥拉帕利联合阿比特龙联合治疗方案的作用，在PFS和OS方面都有显著改善，相比于仅用阿比特龙；而在BRACAWAY试验中，我们了解到PARP抑制剂＋阿比特龙的联合方案具有更优的OS和PFS，相比于单药的序贯使用。

 

当然，所有这些试验都表明基因检测非常重要，如果我们能找出那些携带BRCA1/2突变甚至其他HRR突变的患者，这些mCRPC不同阶段的患者将从加入PARP抑制剂中获益，无论是作为单药治疗还是与ARPI联合治疗。因此，我们应当牢记，基因检测如今是管理mCRPC患者时非常重要的治疗手段。

 

Oncology Frontier:Taking a comprehensive look at the PROfound，PROpel，and BRCAAway studies，how do you assess the clinical application value of APRPi in the mCRPC field?Additionally，what impact does it have on precision treatment for mCRPC?

 

Prof.Darren Poon:I think these three important landmark trials—the PROpel，the PROfound，and the BRACAWAY trial—inform us that the genomic testing is important in the treatment paradigm for the metastatic prostate cancer in different settings.For example，in the PROfound trial，it established the role of PARP inhibitors in mCRPC patients who had prior ARPI and chemotherapy.And in the PROpel trial，it established the role of combination treatments with the olaparib together with abiraterone had a significant improvement in PFS and OS versus the abiraterone alone.Whereas in the BRACAWAY trial，we understand that the combination approaches with the PARP inhibitors together with abiraterone has a more favorable overall survival and PFS compared to the sequential use of the monotherapies.So all these trials showing that the genomic testing is important，and if we could find out patients who harbor the BRCA1，2 mutations or even the other HRR mutations，these patients will be benefit from the additions of PARP inhibitors，either monotherapy or in combinations with the ARPI in different settings of the mCRPC disease.So therefore，we should be bear in mind genomic testing is nowadays a very important treatment approach for the management of mCRPC patients.

 

潘明骏（Darren Poon）教授

养和医院综合肿瘤科中心副主任、临床肿瘤科名誉顾问医生

香港大学临床肿瘤学系名誉临床副教授香港中文大学肿瘤学系名誉临床副教授临床肿瘤科专科医生