Pembrolizumab plus chemotherapy for advanced and recurrent cervical cancer: final analysis according to bevacizumab use in the randomized KEYNOTE-826 study.

This exploratory analysis examined outcomes in patient subgroups defined by bevacizumab use.

这项探索性分析检查了根据贝伐珠单抗使用情况定义的患者亚组的结果。

patients_and_methods

Eligible adult patients had persistent, recurrent, or metastatic squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix not previously treated with chemotherapy and not amenable to curative treatment; measurable disease per RECIST v1.1; and an Eastern Cooperative Oncology Group performance status ≤1.

符合条件的成年患者患有持续性、复发性或转移性鳞状细胞癌、腺鳞癌或宫颈腺癌，之前未接受过化疗治疗且无法进行根治性治疗；根据RECIST v1.1标准有可测量的疾病；以及东部肿瘤协作组（Eastern Cooperative Oncology Group）的体能状态评分为≤1。

Patients were randomly allocated 1 : 1 to pembrolizumab 200 mg every 3 weeks or placebo for up to 35 cycles plus chemotherapy (±bevacizumab 15 mg/kg).

患者按1:1的比例随机分配接受每3周200毫克的帕博利珠单抗或安慰剂，最多进行35个周期的治疗，同时接受化疗（±贝伐珠单抗15 mg/kg）。

Dual primary endpoints were OS and PFS per RECIST v1.1 by investigator assessment.

主要终点是根据研究者评估的RECIST v1.1标准的总生存期（OS）和无进展生存期（PFS）

Outcomes were assessed in subgroups defined by bevacizumab use.

在根据贝伐单抗使用情况定义的亚组中评估了结果。

Hazard ratios (HRs) and 95% confidence intervals (CIs) were based on a stratified Cox regression model.

风险比（HRs）和95%置信区间（CIs）基于分层Cox回归模型得出。

Results

A total of 617 patients were randomly assigned [pembrolizumab arm, n = 308 (63.6% with bevacizumab); placebo arm, n = 309 (62.5% with bevacizumab)].

共有617名患者被随机分配[帕博利珠单抗组，n=308（63.6%伴有贝伐珠单抗）；安慰剂组，n=309（62.5%伴有贝伐珠单抗）]。

The most common reason for bevacizumab exclusion was medical contraindication (75.9%).

排除使用贝伐珠单抗的最常见原因是对药物有医学禁忌（75.9%）。

Among patients who received bevacizumab, HRs (95% CIs) for PFS favored the pembrolizumab arm in the programmed cell death-ligand 1 combined positive score ≥1 [0.56 (0.43-0.73)] and all-comer [0.57 (0.45-0.73)] populations; OS results were 0.60 (0.45-0.79) and 0.61 (0.47-0.80), respectively.

在接受贝伐珠单抗治疗的患者中，对于程序性细胞死亡配体-1联合阳性评分≥1的患者群体[风险比（95%置信区间）为0.56（0.43-0.73）]和所有患者群体[风险比（95%置信区间）为0.57（0.45-0.73）]，无进展生存期（PFS）的结果更倾向于帕博利珠单抗组；总生存期（OS）的结果分别为0.60（0.45-0.79）和0.61（0.47-0.80）。

Among patients who did not receive bevacizumab, HRs (95% CIs) for PFS also favored the pembrolizumab arm in the programmed cell death-ligand 1 combined positive score ≥1 [0.61 (0.44-0.85)] and all-comer [0.69 (0.50-0.94)] populations; OS results were 0.61 (0.44-0.85) and 0.67 (0.49-0.91), respectively.

在未接受贝伐单抗治疗的患者中，程序性细胞死亡配体1综合阳性评分≥1的患者群体，无进展生存期（PFS）的风险比（HRs）及95%置信区间（CIs）也倾向于帕博利珠单抗组[0.61 (0.44-0.85)]，以及所有患者的群体[0.69 (0.50-0.94)]；总生存（OS）的结果分别为0.61 (0.44-0.85)和0.67 (0.49-0.91)。

Among patients who received bevacizumab, grade ≥3 treatment-related adverse events occurred in 74.0% of patients in the pembrolizumab arm and 66.8% in the placebo arm.

在接受贝伐单抗治疗的患者中，帕博利珠单抗组有74.0%的患者出现了3级或更高级别的治疗相关不良事件，而安慰剂组为66.8%。

Conclusions

Pembrolizumab plus chemotherapy prolonged PFS and OS and had manageable safety compared with placebo plus chemotherapy in patient subgroups defined by bevacizumab use.

与安慰剂加化疗相比，帕博利珠单抗联合化疗在贝伐珠单抗使用的患者亚组中延长了无进展生存期（PFS）和总生存期（OS），且安全性可控。