Chalif Julia, Morton Molly, McLaughlin Eric, Gonzalez Anna, Fulton Jessica, Sciuva Jessica, Marcu Ioana, Bixel Kristin L, Cohn David E, Cosgrove Casey M, Copeland Larry J, Nagel Christa I, Backes Floor, O'Malley David M, Spakowicz Daniel J, Chambers Laura M
Division of Gynecologic Oncology; The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute, Columbus, OH, USA.
The Ohio State University School of Biomedical Science, Columbus, OH, USA.
Gynecol Oncol Rep. 2025 Jun 21;60:101782. doi: 10.1016/j.gore.2025.101782. eCollection 2025 Aug.
To assess the effect of medication use during immune checkpoint inhibitor (ICI) therapy on treatment response and oncologic outcomes.
An IRB-approved single-institution retrospective cohort study was performed in patients with endometrial cancer (EC) and cervical cancer (CC) who were treated with ICIs from January 1, 2017 to January 1, 2023. Concomitant medications used during the ICI course were recorded. The associations between medication use and ICI response, progression-free survival (PFS), and overall survival (OS) was assessed.
217 CC and EC patients were treated with ICIs during this study period; 32 % (n = 71) had CC, and 67 % (n = 146) had EC. There was a significant difference in ICI complete response between CC patients who did and did not use oral steroids during treatment. Of CC patients who achieved a complete response, 28 % (n = 7) used steroids vs. 13.6 % (n = 6) of non-steroid users (Fisher's exact p = 0.045). In patients with EC, proton pump inhibitor (PPI) use was associated with ICI response, with 43.8 % (n = 21) of PPI users achieving a complete response vs. 16.3 % (n = 15) of non-PPI users (chi-squared p = 0.002). PPI use in the EC cohort was associated with improved progression-free survival and overall survival (log-rank p < 0.05). This was also demonstrated among mismatch repair-deficient EC patients where PPI use during ICI therapy significantly associated with both PFS (HR 0.26, 95 % CI 0.12-0.55; p < 0.001) and OS (HR 0.22, 95 % CI 0.08-0.59; p < 0.001).Conclusion(s)In this retrospective cohort study of EC and CC patients treated with ICI therapy, medication use, specifically PPIs and oral steroids, was seen to have a significant positive effect on ICI response, PFS, and OS.
评估免疫检查点抑制剂（ICI）治疗期间使用药物对治疗反应和肿瘤学结局的影响。
对2017年1月1日至2023年1月1日接受ICI治疗的子宫内膜癌（EC）和宫颈癌（CC）患者进行了一项经机构审查委员会批准的单机构回顾性队列研究。记录ICI疗程中使用的伴随药物。评估药物使用与ICI反应、无进展生存期（PFS）和总生存期（OS）之间的关联。
在本研究期间，217例CC和EC患者接受了ICI治疗；32%（n = 71）为CC患者，67%（n = 146）为EC患者。在治疗期间使用和未使用口服类固醇的CC患者中，ICI完全缓解率存在显著差异。在实现完全缓解的CC患者中，28%（n = 7）使用了类固醇，而非类固醇使用者为13.6%（n = 6）（Fisher精确检验p = 0.045）。在EC患者中，使用质子泵抑制剂（PPI）与ICI反应相关，43.8%（n = 21）的PPI使用者实现了完全缓解，而非PPI使用者为16.3%（n = 15）（卡方检验p = 0.002）。EC队列中使用PPI与无进展生存期和总生存期改善相关（对数秩检验p < 0.05）。在错配修复缺陷的EC患者中也得到了证实，ICI治疗期间使用PPI与PFS（风险比0.26，95%置信区间0.12 - 0.55；p < 0.001）和OS（风险比0.22，95%置信区间0.08 - 0.59；p < 0.001）均显著相关。
在这项对接受ICI治疗的EC和CC患者的回顾性队列研究中，药物使用，特别是PPI和口服类固醇，对ICI反应、PFS和OS有显著的积极影响。
