Erdafitinib or Erdafitinib Plus Cetrelimab for Patients With Metastatic Urothelial Carcinoma and FGFR Alterations: Final Results From the Phase II NORSE Study.

We conducted a phase II study of erdafitinib, alone or with cetrelimab, in FGFR-altered mUC.

我们进行了一项关于erdafitinib单独或联合cetrelimab治疗FGFR变异型mUC的II期研究。

Methods

Adults with mUC and select FGFR alterations who are ineligible for cisplatin were randomly assigned 1:1 in a noncomparative design to once-daily erdafitinib 8 mg (with pharmacodynamically guided uptitration to 9 mg) or erdafitinib 8 mg plus intravenous cetrelimab 240 mg once every 2 weeks at cycles 1-4 and 480 mg once every 4 weeks thereafter.

对于不符合顺铂治疗条件的具有选择性FGFR改变的mUC成人患者，按照1:1的比例在非比较性设计中随机分配，每天一次接受8毫克的erdafitinib（根据药效动力学指导增加剂量至9毫克）或每天一次接受8毫克的erdafitinib加上每2周一次静脉注射cetrelimab 240毫克（第1-4周期）和此后每4周一次480毫克。

Primary end points were investigator-assessed confirmed overall response rate (ORR) and safety; secondary end points included duration of response (DOR), progression-free survival, and overall survival(OS).

主要终点是研究者评估的确认的总缓解率（ORR）和安全性；次要终点包括缓解持续时间（DOR）、无进展生存期和总生存期（OS）。

No statistical hypotheses were tested.

未进行统计假设检验。

Results

At data cutoff, 87 patients were randomly assigned and treated (erdafitinib, n = 43; erdafitinib plus cetrelimab, n = 44).

在数据截止时，共有87名患者被随机分配并接受了治疗（erdafitinib组，n=43；erdafitinib联合cetrelimab组，n=44）。

Of 64 patients with PD-L1 expression data, 56 (87.5%) had low levels of PD-L1 expression (combined positive score <10).

在有PD-L1表达数据的64名患者中，56名（87.5%）表现出低水平的PD-L1表达（联合阳性评分<10）。

Median survival follow-up was 14.2 months.

中位生存随访期为14.2个月。

Investigator-assessed confirmed ORR for erdafitinib was 44.2% (95% CI, 29.1 to 60.1) with one complete response (CR); median DOR and median OS were 9.7 months (95% CI, 4.6 to not estimable [NE]) and 16.2 months (95% CI, 8.3 to NE), respectively.

研究者评估确认的erdafitinib客观缓解率(ORR)为44.2% (95% 置信区间, 29.1% 至 60.1%)，其中1例为完全缓解(CR)；中位缓解持续时间(DOR)和中位总生存(OS)分别为9.7个月 (95% 置信区间, 4.6个月至不可估计[NE])和16.2个月 (95% 置信区间, 8.3个月至NE)。

Investigator-assessed confirmed ORR for erdafitinib plus cetrelimab was 54.5% (95% CI, 38.8 to 69.6), with six (13.6%) CRs; median DOR and median OS were 11.1 months (95% CI, 8.8 to NE) and 20.8 months (95% CI, 12.0 to NE), respectively.

研究者评估确认的erdafitinib联合cetrelimab客观缓解率(ORR)为54.5% (95% 置信区间, 38.8% 至 69.6%)，其中6例为完全缓解(CR)，占13.6%；中位缓解持续时间(DOR)和中位总生存(OS)分别为11.1个月 (95% 置信区间, 8.8个月至不可估计[NE])和20.8个月 (95% 置信区间, 12.0个月至NE)。

The most frequent treatment-related adverse events (TRAEs) were hyperphosphatemia (83.7% and 68.2% in erdafitinib and erdafitinib plus cetrelimab groups, respectively), stomatitis (69.8% and 56.8%), and dry mouth (37.2% and 56.8%).

最常见的治疗相关不良事件(TRAEs)是高磷血症(在接受erdafitinib和erdafitinib联合cetrelimab治疗的患者中分别为83.7%和68.2%)、口腔炎(分别为69.8%和56.8%)以及口干(分别为37.2%和56.8%)。

Grade ≥3 TRAEs occurred in 46.5% and 45.5% of patients receiving erdafitinib and erdafitinib plus cetrelimab, respectively.

分别有46.5%和45.5%接受erdafitinib和erdafitinib联合cetrelimab治疗的患者出现了3级或以上的TRAEs。

Conclusions

First-line erdafitinib monotherapy and erdafitinib plus cetrelimab demonstrated antitumor activity and a manageable safety profile in cisplatin-ineligible patients with mUC.

一线erdafitinib单药治疗和erdafitinib联合cetrelimab在不适宜使用顺铂的转移性尿路上皮癌患者中显示出抗肿瘤活性和可控的安全性。