Modified Fluorouracil, Leucovorin, Irinotecan, and Oxaliplatin or S-1, Irinotecan, and Oxaliplatin Versus Nab-Paclitaxel + Gemcitabine in Metastatic or Recurrent Pancreatic Cancer (GENERATE, JCOG1611): A Randomized, Open-Label, Phase II/III Trial.

S-1, irinotecan, and oxaliplatin (S-IROX) demonstrated activity in a phase Ib trial in this population.

S-1、伊立替康和奥沙利铂（S-IROX）在这一人群的Ib期试验中显示出活性。

Therefore, these three regimens were directly compared.

因此，这三种治疗方案被直接进行了比较。

Methods

This randomized phase II/III trial was performed at 45 centers in Japan.

这项随机的II/III期临床试验在日本的45个中心进行。

Eligible patients age 20-75 years with an Eastern Cooperative Oncology Group performance status of 0 or 1 and pathologically confirmed metastatic or recurrent pancreatic cancer were randomly assigned (1:1:1) to receive mFOLFIRINOX (oxaliplatin 85 mg/m2 over 2 hours, irinotecan 150 mg/m2 over 90 minutes, l-leucovorin 200 mg/m2 over 2 hours, each once daily on day 1, and fluorouracil 2,400 mg/m2 over 46 hours on days 1-3, every 2 weeks), S-IROX (oxaliplatin 85 mg/m2 over 2 hours, irinotecan 150 mg/m2 over 90 minutes on day 1, and S-1 80 mg/m2/day administered orally twice daily on days 1-7, every 2 weeks), or nab-paclitaxel (125 mg/m2) + gemcitabine (1,000 mg/m2) on days 1, 8, and 15 every 4 weeks.

符合条件的患者年龄在20-75岁之间，东部肿瘤协作组表现状态为0或1，且经病理证实为转移性或复发性胰腺癌，被随机分配（1:1:1）接受mFOLFIRINOX（奥沙利铂85 mg/m2，持续2小时，伊立替康150 mg/m2，持续90分钟，l-亚叶酸钙200 mg/m2，持续2小时，每天一次在第1天，氟尿嘧啶2,400 mg/m2，持续46小时在第1-3天，每2周一次），S-IROX（奥沙利铂85 mg/m2，持续2小时，伊立替康150 mg/m2，持续90分钟在第1天，S-1 80 mg/m2/天，口服，每天两次在第1-7天，每2周一次），或nab-紫杉醇（125 mg/m2）+吉西他滨（1,000 mg/m2）在第1、8和15天，每4周一次。

The primary end point was overall survival(OS).

主要终点是总生存（OS）。

Results

A total of 527 patients were enrolled, with 426 included in the planned interim analysis.

共有527名患者入组，其中426名患者被纳入计划中的中期分析。

The median OS was 14.0 months (hazard ratio[HR], 1.31 [95% CI, 0.97 to 1.77]) and 13.6 months (HR, 1.35 [95% CI, 1.00 to 1.82]) in the mFOLFIRINOX and S-IROX groups, respectively, as compared with 17.1 months in the nab-paclitaxel + gemcitabine group.

mFOLFIRINOX组和S-IROX组的中位总生存期分别为14.0个月（风险比[HR]，1.31 [95% 置信区间，0.97至1.77]）和13.6个月（HR，1.35 [95% 置信区间，1.00至1.82]），与nab-紫杉醇+吉西他滨组的17.1个月相比。

The predictive probability of achieving superiority in the final analysis was <1% in both groups.

在最终分析中，两组达到优越性的预测概率均小于1%。

Thus, the trial was terminated owing to its futility.

因此，由于其无效性，试验被终止。

Grade 3 to 4 anorexia was more frequent in the mFOLFIRINOX (23.3%) and S-IROX (27.5%) groups than in the nab-paclitaxel + gemcitabine group (5.0%).

在mFOLFIRINOX (23.3%)和S-IROX (27.5%)组中，3至4级厌食症的发生率高于nab-紫杉醇+吉西他滨组(5.0%)。

Conclusions

Neither mFOLFIRINOX nor S-IROX appeared to be superior compared with nab-paclitaxel + gemcitabine as the first-line treatment for metastatic or recurrent pancreatic cancer.

在转移性或复发性胰腺癌的一线治疗中，mFOLFIRINOX和S-IROX似乎都不比nab-紫杉醇+吉西他滨更优越。