Overall survival with relacorilant and nab-paclitaxel in patients with platinum-resistant ovarian cancer (ROSELLA): a phase 3 randomised controlled trial.

The efficacy and safety of relacorilant plus nab-paclitaxel were assessed in the phase 3 ROSELLA (GOG-3073, ENGOT-ov72, APGOT-Ov10, and LACOG-0223) trial; the combination showed significant improvement in progression-free survivalamong patients with platinum-resistant ovarian cancer compared with nab-paclitaxel monotherapy.

在第三阶段的ROSELLA（GOG-3073、ENGOT-ov72、APGOT-Ov10和LACOG-0223）试验中评估了relacorilant联合nab-paclitaxel的疗效和安全性；与nab-paclitaxel单药治疗相比，联合治疗在铂类耐药性卵巢癌患者中显示出显著的无进展生存期改善。

Results of the final overall survivalanalysis are reported here.

这里报告了最终总生存分析的结果。

Methods

In this open-label phase 3 trial, patients were randomly assigned 1:1 to receive relacorilant (150 mg orally the day before, day of, and day after nab-paclitaxel infusion) plus nab-paclitaxel (80 mg/m2 intravenously on days 1, 8, and 15 of each 28-day cycle) or nab-paclitaxel monotherapy (100 mg/m2 intravenously on the aforementioned schedule).

在这项开放标签的III期试验中，患者按1:1的比例随机分配接受relacorilant（在nab-paclitaxel输注前一天、当天和后一天口服150毫克）加nab-paclitaxel（每28天周期的第1、8和15天静脉注射80毫克/平方米）或nab-paclitaxel单药治疗（在上述计划中静脉注射100毫克/平方米）。

Patients, aged 18 years or older, with one to three lines of previous anticancer therapy and platinum-resistant disease (progression <6 months from their last dose of platinum) were eligible.

年龄在18岁或以上的患者，之前接受过一至三线抗癌治疗，并且具有铂类耐药疾病（从最后一次铂类药物剂量起进展<6个月）的患者符合入选条件。

The trial was conducted at 117 hospitals and community oncology centres in 14 countries across Australia, Europe, Latin America, North America, and South Korea.

该试验在澳大利亚、欧洲、拉丁美洲、北美和韩国的14个国家的117家医院和社区肿瘤中心进行。

Progression-free survival, assessed by blinded independent central review, and overall survival(time from randomisation to death from any cause) were dual primary endpoints.

无进展生存期（通过盲法独立中央审查评估）和总生存期（从随机分组到因任何原因死亡的时间）是双重主要终点。

Additional prespecified endpoints included safety, second progression-free survival(time from randomisation to disease progression on subsequent anticancer therapy or death due to any cause, whichever occurred first), and patient-reported outcomes.

额外的预先指定终点包括安全性、第二次无进展生存期（从随机分组到在后续抗癌治疗中疾病进展或因任何原因死亡的时间，以先发生者为准）以及患者报告的结果。

This trial is registered at ClinicalTrials.gov, NCT05257408, and is ongoing.

该试验已在ClinicalTrials.gov注册，注册号为NCT05257408，并正在进行中。

Results

Between Jan 5, 2023, and April 8, 2024, 381 patients were randomly assigned to the relacorilant combination group (n=188) or the nab-paclitaxel monotherapy group (n=193).

在2023年1月5日至2024年4月8日期间，381名患者被随机分配到relacorilant联合治疗组（n=188）或nab-paclitaxel单药治疗组（n=193）。

All patients had received bevacizumab; 167 (44%) had received three previous lines of therapy, and 234 (61%) had received a poly(ADP-ribose) polymerase inhibitor.

所有患者均接受过贝伐单抗治疗；167名（44%）患者接受过三种先前的治疗线，234名（61%）患者接受过聚ADP-核糖聚合酶抑制剂。

At a median follow-up of 24·8 months (95% CI 23·6-25·7), the addition of relacorilant to nab-paclitaxel resulted in a statistically and clinically significant improvement in overall survivalcompared with nab-paclitaxel monotherapy (hazard ratiofor death 0·65 [95% CI 0·51-0·83]; p=0·0004); 18-month overall survivalwas 46% and 27%, respectively.

在中位随访24.8个月（95%置信区间23.6-25.7）时，与紫杉醇单药治疗相比，添加relacorilant到紫杉醇治疗显著且临床意义地改善了总生存（死亡风险比为0.65 [95%置信区间0.51-0.83]；p=0.0004）；18个月的总生存率分别为46%和27%。

The median overall survivalin the relacorilant combination group was extended by 4·1 months compared with the nab-paclitaxel monotherapy group (16·0 [95% CI 13·0-18·3] vs 11·9 months [10·0-13·8]).

在 relacorilant 联合治疗组中，中位总生存期比 nab-paclitaxel 单药治疗组延长了4.1个月（16.0个月 [95% 置信区间 13.0-18.3] 对比 11.9个月 [10.0-13.8]）。

Subsequent anticancer treatments were similar across study groups.

随后的抗癌治疗在各研究组之间相似。

Adverse events were similar in both groups when adjusted for duration of study treatment.

在调整研究治疗持续时间后，两组的不良事件相似。

Neutropenia (121 [64%]), anaemia (115 [61%]), fatigue (101 [54%]), and nausea (82 [44%]) were the most common adverse events in the relacorilant combination group.

在 relacorilant 联合用药组中，最常见的不良事件是中性粒细胞减少症（121 例，占64%）、贫血（115 例，占61%）、疲劳（101 例，占54%）和恶心（82 例，占44%）。

No new safety signals were observed with additional follow-up since the primary analysis.

自主要分析以来，随着额外的随访，没有观察到新的安全信号。

interpretation

The addition of relacorilant to nab-paclitaxel led to significantly longer overall survivalin patients with platinum-resistant ovarian cancer, without the need for biomarker selection.

将relacorilant添加到nab-paclitaxel中，使铂耐药性卵巢癌患者的总生存期显著延长，无需进行生物标志物选择。

The findings support relacorilant plus nab-paclitaxel as a potential new standard treatment option for patients with platinum-resistant ovarian cancer.

研究结果支持将relacorilant联合nab-paclitaxel作为铂类耐药性卵巢癌患者的潜在新标准治疗方案。

funding

Corcept Therapeutics.

Corcept Therapeutics公司。