Dostarlimab and niraparib in primary advanced ovarian cancer.

The FIRST/ENGOT-OV44 trial evaluated adding dostarlimab to first-line platinum-based chemotherapy (PBCT) and niraparib maintenance ± bevacizumab in patients with aOC.

FIRST/ENGOT-OV44试验评估了在晚期卵巢癌(aOC)患者中，将dostarlimab添加到一线铂类化疗(PBCT)和niraparib维持治疗±贝伐单抗中的效果。

patients_and_methods

In this randomized, double-blind, phase III trial, patients with newly diagnosed stage III-IV epithelial OC were randomized (1:2) to arm 2 (PBCT-placebo with niraparib maintenance) or arm 3 (PBCT-dostarlimab with dostarlimab-niraparib maintenance); arm 1 (PBCT-placebo with placebo maintenance) enrollment terminated following PARPi approvals.

在这项随机、双盲、III期临床试验中，新诊断为III-IV期上皮性卵巢癌（OC）的患者按1:2的比例随机分配到第2组（PBCT-安慰剂联合niraparib维持治疗）或第3组（PBCT-dostarlimab联合dostarlimab-niraparib维持治疗）；在PARPi获批后，第1组（PBCT-安慰剂联合安慰剂维持治疗）的入组被终止。

Efficacy was assessed in arms 2 and 3 (intention-to-treatpopulation).

在第2组和第3组中评估了疗效（意向治疗人群）。

The primary endpoint was investigator-assessed progression-free survival(PFS) as per RECIST v1.1.

主要终点是根据RECIST v1.1评估的由研究者判定的无进展生存期（PFS）

The key secondary endpoint was overall survival(OS).

关键次要终点是总生存期（OS）

Safety was assessed in patients who received one or more doses of study treatment (arms 1-3; analyzed as per treatment received).

在接收到一次或多次研究治疗的患者中评估了安全性（第1-3组；根据接受的治疗进行分析）。

Results

From 14 November 2018 to 5 January 2021, 1138 patients were randomized to arms 2 (n = 385) and 3 (n = 753) and included in efficacy analyses.

从2018年11月14日至2021年1月5日，共有1138名患者被随机分配到第2组（n=385）和第3组（n=753），并纳入了疗效分析。

Median follow-up was 53.1 (interquartile range 47.5-59.7) months.

中位随访时间为53.1个月（四分位数范围47.5-59.7个月）

There was a statistically significant difference in PFS in arm 3 versus arm 2 (median 20.6 versus 19.2 months; hazard ratio[HR] 0.85, 95% confidence interval[CI] 0.73-0.99, P = 0.0351).

在第3组与第2组之间，无进展生存期（PFS）存在统计学显著差异（中位数分别为20.6个月与19.2个月；风险比[HR]为0.85，95%置信区间[CI]为0.73-0.99，P = 0.0351）。

OS had reached 57% maturity and was not statistically significant (median 44.4 versus 45.4 months; HR 1.01, 95% CI 0.86-1.19, P = 0.9060).

总生存率已达到57%的成熟度，且在统计学上不显著（中位生存期为44.4个月对比45.4个月；风险比为1.01，95%置信区间为0.86-1.19，P = 0.9060）。

Toxicities observed were consistent with known safety profiles of the agents used in the study.

观察到的毒性与研究中使用的药物已知的安全性特征一致。

Conclusions

In the first-line treatment of patients with aOC, the addition of dostarlimab to PBCT and niraparib maintenance was associated with a statistically significant, but clinically modest, PFS improvement, with no difference in OS.

在aOC患者的一线治疗中，将dostarlimab添加到PBCT和niraparib维持治疗中，与统计学上显著但临床效果有限的无进展生存期（PFS）改善相关，总生存（OS）无差异。