ESMO现场直击丨Dr. González-Martín解读PRIMA/ENGOT-ov26/GOG-3012研究最终分析结果

作者:肿瘤瞭望   日期:2024/9/24 11:59:22  浏览量:3068

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《肿瘤瞭望》现场邀请Antonio González-Martín教授分析了这项研究发现的临床意义。

西班牙纳瓦拉大学医院癌症中心Antonio González-Martín教授在2024年ESMO大会汇报了III期PRIMA/ENGOT-OV26/GOG-3012研究(摘要号LBA29)结果。对于患有同源重组缺陷(HRd)的晚期卵巢癌患者,使用尼拉帕利治疗后无进展的可能性是使用安慰剂的两倍,尽管该研究未报告长期总生存(OS)获益。《肿瘤瞭望》现场邀请Antonio González-Martín教授分析了这项研究发现的临床意义。
 
III期PRIMA/ENGOT-OV26/GOG-3012研究主要结果
 
经过约6年的中位随访后,最终OS数据显示,对于新诊断为晚期卵巢癌且复发风险较高的患者,尼拉帕利维持治疗与安慰剂相比没有获益。在总体人群中,尼拉帕利组患者的中位OS为46.6个月,安慰剂组患者的中位OS为48.8个月(风险比<hr/>=1.01);在HRd肿瘤患者中,尼拉帕利组患者的中位OS为71.9个月,安慰剂组患者的中位OS为69.8个月(HR=0.95)。
 
GOG-3012研究:OS
 
研究者评估的PFS更新
 
此前,PRIMA已达到其主要终点,证明在对一线铂类化疗有反应的晚期卵巢癌患者中,无论是否患有HRd肿瘤,一线尼拉帕利维持治疗与安慰剂相比,无进展生存期(PFS)显著延长(N Engl J Med.2019;381:2391–2402)。2024 ESMO大会上公布的特别分析结果显示,在总体人群中,尼拉帕利组的5年PFS率为22%,安慰剂组的5年PFS率为12%。对于HRd肿瘤患者,PFS结果存在显著差异,尼拉帕利组患者无进展的可能性是安慰剂组患者的两倍(5年PFS率分别为35%和16%)。
 
在总体人群中,11.7%的尼拉帕利组患者和37.8%的安慰剂组患者接受了后续PARP抑制剂治疗(在HRd人群中,尼拉帕利15.8%和安慰剂组48.4%的患者接受后续PARP抑制剂治疗)。在HRd患者群体中,尼拉帕利组的至首次后续治疗中位时间比安慰剂组延长(26.9个月vs.13.9个月;HR=0.55)。与安慰剂组相比,尼拉帕利还延长了总体人群的至首次后续治疗的中位时间(17.0个月vs.12.0个月;HR=0.74)。未报告新的安全信号。

2024年ESMO公布了PRIMA/ENGOT-ov26/GOG-3012研究的最终总生存,请问您对尼拉帕利一线维持治疗的新数据有何评价?

Dr.González-Martín:我的名字是Antonio González-Martín。我是一名受过培训的肿瘤内科医生,担任纳瓦拉大学医院癌症中心主任,也是GEICO集团董事长。GEICO是西班牙妇科癌症研究机构。我是PRIMA研究的首席研究员,该研究也被称为ENGOT-OV26/GOG-3012。我很荣幸能够在2024年巴塞罗那举行的ESMO大会上介绍这项重要研究的最终分析结果,包括长期结果和总生存数据。
 
简而言之,在PRIMA研究中,我们将对铂类有应答的高级别浆液性或子宫内膜样卵巢癌患者随机分配到尼拉帕利组或安慰剂组。研究的主要终点是PFS,OS是关键的次要终点。五年前,在这个城市举行的ESMO会议上,我很荣幸地介绍了PRIMA研究的第一次分析结果,证明了在一线铂类治疗有应答的患者中,尼拉帕利作为维持治疗对不同生物标志物亚组患者有益。在2024 ESMO,我介绍了PRIMA研究长期数据。我在2024 ESMO汇报的数据包含三个重要信息。
 
首先,PRIMA研究的长期PFS证实了在HRd人群的一线治疗中添加尼拉帕利作为维持治疗有获益,在五年内,尼拉帕利组的无进展存活患者的比例是安慰剂组患者的两倍(35%vs.16%)。因此,第一个信息是尼拉帕利一线维持治疗对HRd人群具有长期持续益处。
 
其次,PRIMA研究尚未证明OS获益,而OS是关键的次要终点,这可以用两个主要原因来解释。第一个原因是进展后生存期很长。PRIMA研究中进展后生存期中位值极高,五年生存率远高于预期。第二个原因是交叉治疗。在PRIMA研究中,安慰剂组患者后续接受PARP抑制剂治疗的概率是尼拉帕利组的三倍,尤其是对于BRCA突变患者,这一概率为60%。
 
其三,尼拉帕利的长期安全性与众所周知的安全性数据一致。尼拉帕利使用个体化剂量与较低的血液学毒性发生率相关。
 
因此,综合所有这些信息,我们认为PRIMA研究与既往报道是一致的,尼拉帕利作为一线铂类化疗后的维持治疗可为HRd人群患者带来益处。
 
Dr.González-Martín:Hi.My name is Antonio González-Martín.I am the Principal Investigator of the PRIMA study,which is also named ENGOT-OV26/GOG-3012.I had the privilege and honor of presenting at this edition of the ESMO Congress in Barcelona in 2024 the final analysis,including long-term outcomes and the overall survival data,from this important study.
 
To summarize briefly,in the PRIMA study we randomized patients with high-grade serous or endometrioid ovarian cancer who had responded to platinum to niraparib or placebo as maintenance therapy.The primary endpoint of the study was progression-free survival,and the overall survival was a key secondary endpoint.Five years ago,at this conference in this city,I had the honor of presenting the first results of the primary analysis,demonstrating the benefit of niraparib as maintenance therapy for patients who had responded to first-line platinum across the different biomarker subgroups.Yesterday,I presented the long-term data.
 
I would like to give you three important messages.The first is the long-term progression-free survival of our study confirmed the benefit of the addition of niraparib as maintenance therapy in the first-line for the homologous recombination deficiency(HRD)population.Actually,at five years,the rate of patients alive without progression in the niraparib arm is double compared to those patients treated with placebo.It was 35%with niraparib,and 15%with placebo.So the first message is long-term sustained benefit with niraparib in the HRD population.Secondly,we haven’t demonstrated a benefit in overall survival,which was the key secondary endpoint.That could be explained for two main reasons.The first is the long post-progression survival.The median post-progression survival in the PRIMA study was extremely high.The rate of patients alive at five years was much higher than expected.The second reason is because of the crossover therapy.In PRIMA,a three-fold probability of receiving PARP inhibitors was observed in the placebo arm,and in particular for the BRCA-mutated patients,it was 60%.And my final message is that long-term safety with niraparib is consistent with the well-known safety profile of niraparib.As you probably also know,the use of the individualized dose is associated with a lower rate of hematological toxicity.So,taking all this information together,we consider that the PRIMA study is consistent and has demonstrated that niraparib as maintenance after first-line platinum-based chemotherapy provides benefit for our patients in the HRD population.Thank you very much for your attention.
 
参考文献:
1.González-Martín A,et al.Final overall survival(OS)in patients with newly diagnosed advanced ovarian cancer(OC)treated with niraparib first-line(1L)maintenance:results from PRIMA/ENGOT-OV26/GOG-3012.ESMO Congress 2024,LBA29

 

 

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