Department of Gastroenterology and Digestive Oncology, Georges-Pompidou European Hospital, Assistance publique-Hôpitaux de Paris (AP-HP), Sorbonne Paris Cité Paris Descartes University, Paris, France.
Department of Gastroenterology, Poitiers University Hospital, Poitiers, France.
Clin Res Hepatol Gastroenterol. 2020 Jun;44(3):295-301. doi: 10.1016/j.clinre.2019.08.009. Epub 2019 Oct 10.
A combination of nab-paclitaxel plus gemcitabine (N+G) has recently become a standard first-line treatment in patients with metastatic pancreatic adenocarcinoma (MPA), but there are currently no published data concerning second-line treatment after N+G. The aim of this study was to evaluate the survival outcomes and tolerability of three usual fluoropyrimidine-based regimens FOLFOX, FOLFIRI and FOLFIRINOX after N+G failure in MPA patients.
Patients receiving N+G as first-line regimen were prospectively identified in 11 French centers between January 2014 and January 2017. After disease progression or unacceptable toxicity, patients eligible for second-line therapy were enrolled in the study. The primary endpoint was overall survival following the second-line regimen. Secondary endpoints were objective response, progression-free survival and safety.
Out of 137 patients treated with N+G as first-line regimen, 61 (44.5%) received second-line chemotherapy, including FOLFOX (39.4%), FOLFIRI (34.4%) or FOLFIRINOX (26.2%). Baseline characteristics were not different between the 3 groups. In particular, median age was 71.7 years, sex ratio was 1/1, and performance status (PS) was 0 in 11.5% of case. Main grade 3 toxicities were neutropenia (4.9%) and nausea (3.3%), without major differences between the groups. No toxic death was observed. Median second-line progression-free survival (PFS) and overall survival (OS) were 2.95 (95% CI: 2.3-5.4) and 5.97 months (95% CI: 4.0-8.0), respectively, with no difference between the 3 groups. Median OS from the start of first-line chemotherapy was 12.7 months (10.4-15.1) and was significantly better in patients receiving FOLFIRI after N+G failure, 18.4 months (95% CI: 11.7-24.1, P<0.05), as compared with FOLFOX or FOLFIRINOX (10.4 and 12.3 months, respectively).
This study suggests that second-line fluoropyrimidine-based regimens after N+G failure are feasible, have a manageable toxicity profile in selected patients with MPA, and are associated with promising clinical outcomes, in particular when combined with irinotecan. Randomized phase 3 trials are needed to confirm this trend.
纳武利尤单抗联合吉西他滨（N+G）最近已成为转移性胰腺腺癌（MPA）患者的一线标准治疗方案，但目前尚无关于 N+G 治疗失败后的二线治疗数据。本研究旨在评估 N+G 治疗失败后的转移性胰腺腺癌患者接受三种常用氟嘧啶类方案（FOLFOX、FOLFIRI 和 FOLFIRINOX）的生存结果和耐受性。
2014 年 1 月至 2017 年 1 月期间，11 家法国中心前瞻性地确定了接受 N+G 作为一线治疗方案的患者。在疾病进展或不可接受的毒性后，符合二线治疗条件的患者被纳入研究。主要终点是二线治疗后的总生存期。次要终点是客观缓解率、无进展生存期和安全性。
在 137 例接受 N+G 作为一线治疗方案的患者中，61 例（44.5%）接受了二线化疗，包括 FOLFOX（39.4%）、FOLFIRI（34.4%）或 FOLFIRINOX（26.2%）。三组间基线特征无差异。中位年龄为 71.7 岁，男女比例为 1:1，体能状态（PS）为 0 的占 11.5%。主要的 3 级毒性为中性粒细胞减少症（4.9%）和恶心（3.3%），各组间无显著差异。未观察到治疗相关的死亡。中位二线无进展生存期（PFS）和总生存期（OS）分别为 2.95 个月（95%CI：2.3-5.4）和 5.97 个月（95%CI：4.0-8.0），三组间无差异。从一线化疗开始的中位 OS 为 12.7 个月（10.4-15.1），N+G 治疗失败后接受 FOLFIRI 治疗的患者中位 OS 明显更好，为 18.4 个月（95%CI：11.7-24.1，P<0.05），而接受 FOLFOX 或 FOLFIRINOX 的患者中位 OS 分别为 10.4 个月和 12.3 个月。
本研究表明，N+G 治疗失败后接受氟嘧啶类二线治疗方案是可行的，在选择的 MPA 患者中具有可管理的毒性特征，并与有前途的临床结果相关，特别是与伊立替康联合使用时。需要开展随机 3 期临床试验来证实这一趋势。
