PRODIGE-23 研究显示，就疾病而言，FOLFIRINOX（5-氟尿嘧啶、伊立替康和奥沙利铂）作为诱导化疗后进行长程放化疗 (CTRT) 比单独新辅助 CTRT 后进行全直肠系膜切除 (TME) 具有更高的益处-局部晚期直肠癌（LARC）的无生存期（DFS）和总生存期（OS）。伊立替康强化治疗相对于氟嘧啶和奥沙利铂双联诱导的附加值仍存在争议。为了评估生存率、病理完全缓解 (pCR) 率和安全性，通过比较三联和双联诱导后进行 CTRT 的 II-III 期试验在对 PubMed、Embase、Cochrane、美国临床肿瘤学会和欧洲肿瘤内科学会会议图书馆进行系统文献回顾后，从 II-III 期临床试验中提取 Kaplan-Meier (KM) 曲线数据。选择了 II-III 期试验，其中包括至少一个治疗组，采用不使用生物制剂的双重或三重诱导化疗至少 3 个月，然后进行长程 CTRT 和 TME，并进行至少 48 个月的随访。当可用时，所选研究的新辅助 CTRT 单独组被纳入作为比较参考治疗。通过图形重建，从 2024 年 4 月 10 日至 5 月 19 日期间的原始试验的 Kaplan-Meier 图中提取个体患者的 DFS 和 OS 数据。进行了汇总分析，并在随后的网络荟萃分析 (NMA) 中验证了结果。还收集了 pCR 率和 ≥ 3 级不良事件率。主要终点是三联体和双联体诱导之间的 DFS 和 OS。次要终点是单独新辅助 CTRT 与三联或双联诱导之间的 DFS 和 OS，以及不同组之间的 pCR 率和安全性概况。 在 3 项试验中入组的 674 名患者中，231 名、161 名和 282 名患者接受 FOLFIRINOX 或 CAPOX（卡培他滨和卡培他滨）治疗。奥沙利铂）随后分别进行 CTRT 或单独新辅助 CTRT。三胞胎诱导的 5 年 DFS 率为 73.1% [95%CI：67.2% - 79.0%]、61.7% [95%CI：53.9% - 69.5%] 和 65.1% [95%CI：59.4% - 70.8%] 、双重诱导和单独新辅助 CTRT。 FOLFIRINOX 的 5 年 OS 率为 86.8 % [95 % CI：82.3 % - 91.3 %]、74.7 % [95 % CI：67.6 % - 81.8 %] 和 79.6 % [95 % CI：74.9 % - 84.3 %] 、CAPOX 和单独新辅助 CTRT。三联体诱导显示出相对于双联体诱导更长的 DFS 和 OS（DFS 的 HR：0.67 [95% CI 0.47 - 0.96]，p = 0.03；OS 的 HR：0.49 [95% CI 0.31 - 0.78]，p = 0.003）与单独新辅助 CTRT 相比的优越性趋势（DFS 的 HR：0.77 [95% CI 0.57 - 1.05]，p = 0.10；OS 的 HR：0.67 [95% CI 0.45 - 1.01]，p = 0.06）。双联诱导组和新辅助 CTRT 组之间没有观察到差异。与接受 CAPOX 治疗的受试者 (19.7%，p = 0.02) 或单独新辅助 CTRT 治疗的受试者 (12.5%，p < 0.0001) 相比，接受 FOLFIRINOX 治疗的患者的 pCR 率较高 (27.7%)。与双联体诱导相比，三联体与严重中性粒细胞减少症（17% vs 1%，p < 0.0001）和恶心呕吐（11% vs 3%，p = 0.02）的发生率较高相关。使用 FOLFIRINOX 诱导显示出更好的生存结果和 pCR 率相对于 CAPOX，代价是 G3-4 中性粒细胞减少症和恶心/呕吐增加。一项在总体新辅助治疗策略框架内比较三联化疗和双联化疗的随机研究得到了广泛的支持。版权所有 © 2024 Elsevier Ltd。保留所有权利。

The PRODIGE-23 study showed a higher benefit for FOLFIRINOX (5-fluorouracil, irinotecan and oxaliplatin) as induction chemotherapy followed by long-course chemoradiotherapy (CTRT) respect to neoadjuvant CTRT alone both followed by total mesorectal excision (TME) in terms of disease-free survival (DFS) and overall survival (OS) in locally advanced rectal cancer (LARC). The added value of treatment intensification with irinotecan, over the doublet induction with fluoropyrimidine and oxaliplatin is still debated.To assess survival, pathological complete response (pCR) rate, and safety from phase II-III trials comparing triplet and doublet induction both followed by CTRT and TME in LARC.After a systematic literature review of PubMed, Embase, Cochrane, American Society of Clinical Oncology and European Society for Medical Oncology meetings' libraries, data from Kaplan-Meier (KM) curves were extracted from phase II-III clinical trials. Phase II-III trials including at least one treatment arm with doublet or triplet induction chemotherapy without biological agents administered for a minimum of 3 months followed by long-course CTRT and TME and with at least 48 months of follow-up were selected. When available, the neoadjuvant CTRT alone arms of the selected studies were included as a comparator reference treatment. Individual patient DFS and OS data were extracted from Kaplan-Meier plots of original trials through graphical reconstruction between April 10th and May 19th, 2024. A pooled analysis was conducted, and results were validated in a subsequent network meta-analysis (NMA). pCR rates and grade ≥ 3 adverse events rates were also collected. Primary endpoints were DFS and OS between triplet and doublet induction. Secondary endpoints were DFS and OS between neoadjuvant CTRT alone and triplet or doublet induction as well as pCR rates and safety profile among different arms.Out of 674 patients enrolled in 3 trials, 231, 161 and 282 were treated with FOLFIRINOX or CAPOX (capecitabine and oxaliplatin) followed by CTRT or neoadjuvant CTRT alone, respectively. 5-year DFS rates were 73.1 % [95 %CI: 67.2 % - 79.0 %], 61.7 % [95 %CI: 53.9 % - 69.5 %] and 65.1 % [95 %CI: 59.4 % - 70.8 %] for triplet induction, doublet induction, and neoadjuvant CTRT alone, respectively. 5-year OS rates were 86.8 % [95 %CI: 82.3 % - 91.3 %], 74.7 % [95 %CI: 67.6 % - 81.8 %], and 79.6 % [95 %CI: 74.9 % - 84.3 %] for FOLFIRINOX, CAPOX, and neoadjuvant CTRT alone, respectively. Triplet induction showed longer DFS and OS respect to doublet induction (HR for DFS: 0.67 [95 % CI 0.47 - 0.96], p = 0.03; HR for OS: 0.49 [95 % CI 0.31 - 0.78], p = 0.003) with a trend for superiority when compared with neoadjuvant CTRT alone (HR for DFS: 0.77 [95 % CI 0.57 - 1.05], p = 0.10; HR for OS: 0.67 [95 % CI 0.45 - 1.01], p = 0.06). No difference was observed between the doublet induction and neoadjuvant CTRT groups. pCR rates were higher for patients treated with FOLFIRINOX (27.7 %) respect to subjects receiving CAPOX (19.7 %, p = 0.02) or neoadjuvant CTRT alone (12.5 %, p < 0.0001). Triplet was associated with higher rates of severe neutropenia (17 % vs 1 %, p < 0.0001) and nausea-vomiting (11 % vs 3 %, p = 0.02) respect to doublet induction.Induction with FOLFIRINOX showed better survival outcomes and pCR rates respect to CAPOX at the price of increased G3-4 neutropenia and nausea/vomiting. A randomized study comparing triplet and doublet chemotherapy in the frame of a total neoadjuvant treatment strategy is widely warranted.Copyright © 2024 Elsevier Ltd. All rights reserved.