Background

Several randomised controlled trials (RCTs) have reported various systemic adjuvant therapy regimens following resection of pancreatic ductal adenocarcinoma (PDAC). The most commonly applied include modified FOLFRINOX (mFFX), Gemcitabine/Capecitabine (GemCap) and S1, usually compared to gemcitabine (Gem) alone. However, many of these regimens have not been directly compared in RCTs. This network meta-analysis aims to characterise the impact of adjuvant therapies on overall and disease-free survival in patients having resection of PDAC.

Methods

A systematic review was conducted using MEDLINE, EMBASE, Cochrane Central and American Society of Clinical Oncology (ASCO) abstracts to identify published phase III RCTs articles up to 9th May 2019 that examined adjuvant systemic therapy in resected pancreatic cancer. Data including study characteristics and outcomes including overall survival (OS) and disease-free survival (DFS) were extracted. Indirect comparisons of all regimens were simultaneously compared using random-effects network meta-analyses (NMA) which maintains randomisation within trials.

Results

Twelve phase III RCTs involving 4947 patients and nine different regimens (5-Flourouracil/Folinic acid (5-FU/FA), Gemcitabine, Gemcitabine/Erlotinib (GemErl), GemCap), mFFX, S1, chemoradiotherapy (CRT), CRT with either 5-FU or Gemcitabine) were identified. S1 was ranked best for overall and disease-free survival followed by mFFX. Whilst there were no significant difference between S1 and mFFX for overall survival (mean difference: 1.6 months, p = 0.8), S1 had significantly longer disease-free survival than mFFX (mean difference: 2.8 months, p < 0.001). Furthermore, S1 was ranked best for lowest overall and haematological grade 3/4 toxicities.

Conclusion

This network meta-analysis demonstrates that chemotherapy with S1 or mFFX is superior to GemCap for adjuvant treatment for PDAC, improves survival after surgical resection and should be considered as reasonable standard treatment options in the adjuvant setting and as control arm for future adjuvant clinical trials.

中文翻译：

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胰腺导管腺癌 (PDAC) 切除术后辅助治疗的 III 期随机对照试验的系统评价和网络荟萃分析。

背景

几项随机对照试验 (RCT) 报告了胰腺导管腺癌 (PDAC) 切除术后的各种全身辅助治疗方案。最常用的包括改良的 FOLFRINOX (mFFX)、吉西他滨/卡培他滨 (GemCap) 和 S1，通常与单独的吉西他滨 (Gem) 进行比较。然而，这些方案中有许多尚未在 RCT 中直接进行比较。该网络荟萃分析旨在表征辅助治疗对 PDAC 切除术患者的总体生存率和无病生存率的影响。

方法

使用 MEDLINE、EMBASE、Cochrane 中美洲临床肿瘤学会 (ASCO) 摘要进行了系统评价，以确定截至 2019 年 5 月 9 日已发表的 III 期 RCT 文章，这些文章检查了切除胰腺癌的辅助全身治疗。提取的数据包括研究特征和结果，包括总生存期 (OS) 和无病生存期 (DFS)。使用随机效应网络荟萃分析 (NMA) 同时比较所有方案的间接比较，该分析在试验中保持随机化。

结果

十二项 III 期 RCT 涉及 4947 名患者和九种不同方案（5-氟尿嘧啶/亚叶酸（5-FU/FA）、吉西他滨、吉西他滨/厄洛替尼（GemErl）、GemCap）、mFFX、S1、放化疗（CRT）、CRT 5-FU 或吉西他滨）。S1 在总体和无病生存率方面排名最佳，其次是 mFFX。虽然 S1 和 mFFX 的总生存期没有显着差异（平均差异：1.6 个月，p = 0.8），但 S1 的无病生存期明显长于 mFFX（平均差异：2.8 个月，p < 0.001）。此外，S1 的总体毒性和血液学 3/4 级毒性最低，排名最高。

结论

该网络荟萃分析表明，S1 或 mFFX 化疗在 PDAC 的辅助治疗方面优于 GemCap，可提高手术切除后的生存率，应被视为辅助治疗中合理的标准治疗选择，并作为未来辅助临床试验的对照组。