Hu Ya-Fei, Hu Hai-Jie, Kung Heng-Chung, Lv Tian-Run, Yu Jun, Li Fu-Yu
Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD, United States.
Front Oncol. 2023 Oct 25;13:1267577. doi: 10.3389/fonc.2023.1267577. eCollection 2023.
The efficacy of platinum-based chemotherapy (PtCh) for pancreatic cancer (PC) patients with DNA damage repair gene mutations (DDRm) compared to those without DDRm remains uncertain.
After a thorough database searching in PubMed, Embase, and Web of Science, a total of 19 studies that met all the inclusion criteria were identified. The primary outcomes were overall survival (OS) and progression-free survival (PFS) for PC patients with DDRm versus those without DDRm after PtCh.
Patients with advanced-stage PC who have DDRm tend to have longer OS compared to patients without DDRm, regardless of their exposure to PtCh (HR=0.63; I = 66%). Further analyses indicated that the effectiveness of PtCh for OS was modified by DDRm (HR=0.48; I = 59%). After the first- line PtCh (1L-PtCh), the PFS of advanced-stage PC with DDRm was also significantly improved (HR=0.41; I = 0%). For patients with resected PC, regardless of their exposure to PtCh, the OS for patients with DDRm was comparable to those without DDRm (HR=0.82; I = 71%). Specifically, for patients with resected PC harboring DDRm who received PtCh (HR=0.85; I = 65%) and for those after non-PtCh (HR=0.87; I = 0%), the presence of DDRm did not show a significant association with longer OS.
1L-PtCh treatment is correlated with favorable survival for advanced-stage PC patients with DDRm. For resected-stage PC harboring DDRm, adjuvant PtCh had limited effectiveness. The prognostic value of DDRm needs to be further verified by prospective randomized controlled trials.
https://www.crd.york.ac.uk/prospero/, identifier CRD42022302275.
与无DNA损伤修复基因突变（DDRm）的胰腺癌（PC）患者相比，铂类化疗（PtCh）对有DDRm的PC患者的疗效仍不确定。
在PubMed、Embase和Web of Science中进行全面的数据库检索后，共确定了19项符合所有纳入标准的研究。主要结局是有DDRm与无DDRm的PC患者在接受PtCh后的总生存期（OS）和无进展生存期（PFS）。
无论是否接受PtCh，有DDRm的晚期PC患者的OS往往比无DDRm的患者更长（HR=0.63；I²=66%）。进一步分析表明，DDRm改变了PtCh对OS的有效性（HR=0.48；I²=59%）。一线PtCh（1L-PtCh）后，有DDRm的晚期PC的PFS也显著改善（HR=0.41；I²=0%）。对于接受了手术切除的PC患者，无论是否接受PtCh，有DDRm的患者的OS与无DDRm的患者相当（HR=0.82；I²=71%）。具体而言，对于接受PtCh的有DDRm的手术切除PC患者（HR=0.85；I²=65%）和未接受PtCh的患者（HR=0.87；I²=0%），DDRm的存在与更长的OS无显著关联。
1L-PtCh治疗与有DDRm的晚期PC患者的良好生存相关。对于有DDRm的手术切除期PC，辅助PtCh的有效性有限。DDRm的预后价值需要通过前瞻性随机对照试验进一步验证。
