TRYBECA-1: A Randomized Phase III Study of Eryaspase Combined With Chemotherapy Versus Chemotherapy as Second-Line Treatment in Patients With Advanced Pancreatic Adenocarcinoma.

patients_and_methods

TRYBECA-1 enrolled patients 18 years and older whose disease progressed on or after 1L chemotherapy.

TRYBECA-1研究招募了18岁及以上的患者，这些患者的疾病在一线化疗后进展或恶化。

Patients were randomly assigned to eryaspase plus chemotherapy (gemcitabine/nab-paclitaxel or fluorouracil [5-FU], leucovorin [LV], and irinotecan/nanoliposomal irinotecan) or chemotherapy.

患者被随机分配接受红细胞生成酶联合化疗（吉西他滨/白蛋白结合型紫杉醇或氟尿嘧啶[5-FU]，亚叶酸[LV]和伊立替康/纳米脂质体伊立替康）或仅接受化疗。

Treatment was administered in a 4-week cycle for each of the following drugs until disease progression or unacceptable toxicity: eryaspase 100 U/kg intravenously on days 1 and 15; gemcitabine 1,000 mg/m2 and nab-paclitaxel 125 mg/m2 intravenously on days 1, 8 and 15; irinotecan 180 mg/m2 (or nanoliposomal irinotecan 70 mg/m2) intravenously on days 1 and 15; 5-FU 2,400 mg/m2 as one 46-hour infusion (with a bolus of 400 mg/m2); and LV 400 mg/m2 intravenously on days 1 and 15.

每种药物的治疗以4周为一个周期，直至疾病进展或出现不可接受的毒性反应：在第1天和第15天静脉注射红细胞生成酶100 U/kg；在第1天、第8天和第15天静脉注射吉西他滨1,000 mg/m2和白蛋白结合型紫杉醇125 mg/m2；在第1天和第15天静脉注射伊立替康180 mg/m2（或纳米脂质体伊立替康70 mg/m2）；在46小时的输液中静脉注射5-FU 2,400 mg/m2（首剂量为400 mg/m2）；在第1天和第15天静脉注射LV 400 mg/m2。

The primary end point was overall survival(OS); secondary end points included progression-free survival(PFS), objective response rate(ORR), and safety.

主要终点是总生存（OS）；次要终点包括无进展生存（PFS）、客观缓解率（ORR）和安全性。

Results

A total of 512 patients were randomly assigned (n = 255 for eryaspase and n = 257 for chemotherapy alone).

共有512名患者被随机分配（红细胞天青酶组255人，单纯化疗组257人）。

Baseline characteristics were balanced between the two groups.

两组基线特征均衡。

There were 420 deaths, with a median OS of 7.5 months for eryaspase and chemotherapy versus 6.7 months for chemotherapy (hazard ratio[HR], 0.92 [95% CI, 0.76 to 1.11]; P = .374); the median PFS was 3.7 months versus 3.4 months (HR, 0.88 [95% CI, 0.73 to 1.07]; P = .196), and the ORR was 16.1% versus 12.5% (odds ratio, 1.35; [95% CI, 0.81 to 2.24]), respectively.

共有420例死亡，红细胞天青酶联合化疗组的中位总生存期为7.5个月，而单纯化疗组为6.7个月（风险比[HR]，0.92 [95% 置信区间，0.76至1.11]；P = .374）；无进展生存期（PFS）的中位数分别为3.7个月和3.4个月（HR，0.88 [95% 置信区间，0.73至1.07]；P = .196），客观缓解率（ORR）分别为16.1%和12.5%（比值比，1.35；[95% 置信区间，0.81至2.24]）。

Grade ≥3 adverse events (AEs) included neutropenia (25.4% v 20.3%), asthenia (16.9% v 13.8%), and anemia (17.3% v 12.2%) in the experimental versus control arms, respectively.

3级或以上不良事件(AE)包括中性粒细胞减少症(实验组25.4%，对照组20.3%)、乏力(实验组16.9%，对照组13.8%)和贫血(实验组17.3%，对照组12.2%)。

Conclusions

The addition of eryaspase to chemotherapy did not improve OS, PFS, or ORR.

红细胞生成素酶联合化疗并未改善总生存(OS)、无进展生存(PFS)或客观缓解率(ORR)。

AEs were generally consistent with previous reports of chemotherapy.

不良事件总体上与化疗的先前报告一致。

These results do not support additional development of eryaspase in PDAC.

这些结果不支持在PDAC中进一步开发eryaspase。