LBA5500
TRUST: Trial of radical upfront surgical therapy in advanced ovarian cancer (ENGOT ov33/AGO‐OVAR OP7).
TRUST：晚期卵巢癌根治性初始手术治疗试验(ENGOT ov33/AGO-OVAR OP7)
First Author: Sven Mahner, Department of Obstetrics and Gynecology, University Hospital, Ludwig-Maximilians-Universit¨at M¨unchen,Munich, Germany
Background
Optimal timing of cytoreduction in non-frail patients (pts) with seemingly resectable stage IIIB-IVB ovarian, tubal, and peritoneal carcinoma (OC) remains controversial.
研究背景
在看似可切除的IIIB-IVB期体能状态良好卵巢癌、输卵管癌和腹膜癌(OC)患者中减瘤术最佳时机仍存在争议。
Methods
TRUST is an international randomized multicenter phase III trial in pts with stage IIIB-IVB OC and good performance status (ECOG 0/1) comparing primary cytoreductive surgery (PCS) followed by 6 cycles of intravenous (iv) chemotherapy to 3 cycles of neoadjuvant iv chemotherapy (NACT) followed by interval cytoreductive surgery (ICS) and 3 further iv cycles. Maintenance treatment with bevacizumab and/or PARP inhibitors was allowed if selection criteria was similar for both arms. Pts were eligible for the study if preoperative clinical and radiologic assessment identified them as potential candidates for PCS. To ensure surgical quality, participating centers complied with an onsite surgery quality assurance audit, had adequate infrastructure, surgical proficiency (complete resection rates ≥50% in PCS) and sufficient volume (≥36 PCS/year). The intent to treat analysis population included all eligible pts with confirmed stage IIIB-IVB disease. The primary endpoint was overall survival (OS). Superiority was tested using a two-sided stratified log-rank test with significance level 0.05. Secondary endpoints were progression-free survival (PFS) and surgical complications.
研究方法
TRUST是一项针对IIIB-IVB期体能状态良好(ECOG 0/1)卵巢癌(OC)患者的国际性、随机、多中心III期试验，目的是比较初始减瘤术(PCS)后接受6个周期的静脉(iv)化疗与3个周期新辅助静脉化疗(NACT)后进行间歇性减瘤术(ICS)再接受3个周期静脉化疗的疗效差异。若两种方案的选择标准一致，允许使用贝伐珠单抗和/或PARP抑制剂进行维持治疗。入组患者需符合术前临床和影像学评估确定PCS的潜在适应症。为确保手术质量，参与中心需遵守现场手术质量保证审核，基础设施完备、手术熟练(PCS完全切除率≥50%)以及手术量足够(年PCS≥36次)。意向性治疗分析人群包括所有确诊为IIIB-IVB期的入组患者。主要终点是总生存期(OS)。采用双侧分层对数秩检验进行优效性检验，显著性水平为0.05。次要终点为无进展生存期(PFS)和手术并发症。
Results
A total of 688 eligible pts (median age: 63y; range: 32-83) underwent randomization: 345 were assigned to PCS and 343 to NACT/ICS. 91% had high-grade serous histology. Complete resection was achieved in 61.7%/62.9% of all randomized/all operated pts in the PCS group and 72%/76.6% in the ICS group. Median PFS was 22.2 months in the PCS group, and 19.7 months in the ICS group (HR 0.80 95%CI: 0.66-0.96; p=0.02). Median OS was 54.3 months in the PCS group and 48.3 months in the ICS group (HR 0.89 95%CI: 0.74-1.08; p=0.24). Pts with complete cytoreduction after PCS had the most favorable outcome, with a median PFS and OS of 27.9 and 67.0 months, respectively. A long-term benefit from PCS was seen in all analyzed subgroups. The benefit of PCS was most prominent in stage III pts (n=468): median PFS for PCS vs ICS, 26.3 vs 21.4 mos; median OS for PCS vs ICS, 63.7 vs 53.2 months. Major postoperative complication rates were acceptable, with a 30-day postoperative mortality rate of < 1% in both groups.
研究结果
共纳入688例患者(中位年龄：63岁；范围：32 – 83岁)接受随机分配：345例被分配到PCS组，343例被分配到NACT/ICS组。91%的患者为高级别浆液性组织学类型。在PCS组中，所有随机分配/所有接受手术的患者中分别有61.7%/62.9%实现了完全切除，而在ICS组中，这一比例为72%/76.6%。PCS组的中位PFS为22.2个月，ICS组为19.7个月(HR 0.80，95%CI：0.66 – 0.96；p=0.02)。PCS组的中位OS为54.3个月，ICS组为48.3个月(HR 0.89，95% CI：0.74 – 1.08；p=0.24)。在PCS后实现完全减瘤的患者预后最佳，中位PFS和OS分别为27.9个月和67.0个月。在所有分析的亚组中均观察到PCS的长期获益。在III期患者(n=468)中，PCS的获益最为显著：PCS组与ICS组的中位PFS分别为26.3个月和21.4个月；中位OS分别为63.7个月和53.2个月。两组的主要术后并发症发生率均可接受，术后30天死亡率均<1%。
Conclusions
In expert centers with proven surgical quality, PCS followed by iv chemotherapy resulted in a significantly longer median PFS and a numerically longer OS compared to NACT/ICS in non-frail OC pts. Although statistical significance in the primary endpoint was not reached, this is the first randomized trial to show a benefit of PCS over ICS. This benefit is likely to be associated with the high complete resection rate, reinforcing PCS as a standard of care in non-frail pts with seemingly resectable advanced OC.
研究结论
在手术质量经认证的专业中心，对于体能状态良好的卵巢癌患者，相较于新辅助化疗联合间歇手术(NACT/ICS)，初始肿瘤细胞减灭术(PCS)联合静脉化疗可显著延长中位PFS，OS也获得延长趋势。尽管主要终点(OS)未达统计学显著性，但这是首个证明PCS优于ICS的随机试验。该获益可能与高完全切除率相关，进一步巩固了PCS作为体能良好、看似可切除的晚期卵巢癌患者标准治疗的地位。
林仲秋教授点评：
本研究再次证明如下观点：PCS的R0的预后优于ICS的R0，ICS的R0的预后相当于PCS的R1。初次手术非常重要！
