Over the past two decades, our group has conducted five multicenter trials focusing on first-line systemic therapy for patients with advanced pancreatic cancer. The current pooled analysis was designed to evaluate prognosis over time and the impact of clinical characteristics on survival. Individual patient data were derived from five prospective, controlled, multicenter trials conducted by the ‘Arbeitsgemeinschaft Internistische Onkologie’ (AIO): ‘Gem/Cis’, ‘Ro96’, ‘RC57’, ‘ACCEPT’ and ‘RASH’, which recruited patients between December 1997 and January 2017. Overall, 912 patients were included. The median overall survival (OS) for all assessable patients was 7.1 months. OS significantly improved over time, with a median OS of 8.6 months for patients treated from 2012 to 2017 compared with 7.0 months from 1997 to 2006 [hazard ratio (HR) 1.06; < 0.004]. Eastern Cooperative Oncology Group performance status (HR 1.48; < 0.001), use of second-line treatment (HR 1.51; < 0.001), and Union for International Cancer Control (UICC) stage (III versus IV) (HR 1.34, = 0.002) had a significant impact on OS. By contrast, no influence of age and gender on OS was detectable. Comparing combination therapy with single-agent chemotherapy did not demonstrate a survival benefit, nor did regimens containing epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) such as afatinib or erlotinib, compared with chemotherapy-only arms. Patients with early-onset pancreatic cancer (age at study entry of ≤50 years, = 102) had a similar OS compared with those >50 years (7.1 versus 7.0 months; HR 1.13; = 0.273). The use of a platinum-containing regimen was not associated with better outcomes in patients with early-onset pancreatic cancer. Within this selected group of patients treated within prospective clinical trials, survival has shown improvement over two decades. This effect is likely attributable to the availability of more effective combination therapies and treatment lines, rather than to any specific regimen, such as those containing EGFR-TKIs. In addition, concerning age and sex subgroups, the dataset did not provide evidence for distinct clinical behavior.

中文翻译：

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晚期胰腺癌全身化疗治疗过程随时间的变化：德国 AIO 研究小组二十年来五项临床试验的汇总分析

在过去的二十年里，我们小组进行了五项多中心试验，重点关注晚期胰腺癌患者的一线系统治疗。当前的汇总分析旨在评估随时间变化的预后以及临床特征对生存的影响。个体患者数据来自“Arbeitsgemeinschaft Internistische Onkologie”(AIO) 进行的五项前瞻性、对照、多中心试验：“Gem/Cis”、“Ro96”、“RC57”、“ACCEPT”和“RASH”，这些试验招募了患者1997 年 12 月至 2017 年 1 月期间。总共纳入了 912 名患者。所有可评估患者的中位总生存期 (OS) 为 7.1 个月。随着时间的推移，OS 显着改善，2012 年至 2017 年接受治疗的患者的中位 OS 为 8.6 个月，而 1997 年至 2006 年为 7.0 个月[风险比 (HR) 1.06； < 0.004]。东部肿瘤合作组的表现状态（HR 1.48；< 0.001）、二线治疗的使用（HR 1.51；< 0.001）和国际癌症控制联盟（UICC）分期（III 与 IV）（HR 1.34，= 0.002）对操作系统有重大影响。相比之下，没有检测到年龄和性别对 OS 的影响。与单药化疗相比，联合治疗与单药化疗并没有显示出生存获益，含有表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）（例如阿法替尼或厄洛替尼）的治疗方案与仅化疗组相比也没有显示出生存获益。早发性胰腺癌患者（进入研究时的年龄≤50岁，= 102）与> 50岁的患者具有相似的OS（7.1个月与7.0个月；HR 1.13；= 0.273）。使用含铂方案与早发性胰腺癌患者的更好预后无关。在前瞻性临床试验中接受治疗的这组选定的患者中，二十年来生存率有所改善。这种效果可能归因于更有效的联合疗法和治疗系列的出现，而不是任何特定的治疗方案，例如含有 EGFR-TKI 的治疗方案。此外，关于年龄和性别亚组，数据集没有提供不同临床行为的证据。