Braganca Xavier Camila, Andersen Clark R, Lim JoAnn, Slade Julian H, Bean Stacie A, Kang Lei, Le Hung, Tsimberidou Apostolia M, Naing Aung, Hong David S, Dumbrava Ecaterina E, Rodon Ahnert Jordi, Pohlmann Paula R, Piha-Paul Sarina A, Champiat Stephane, Yap Timothy A, Tang Tin-Yun, Meric-Bernstam Funda, Fu Siqing
Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Cancer Res Commun. 2025 Sep 1;5(9):1631-1641. doi: 10.1158/2767-9764.CRC-25-0033.
Concurrent use of medications can modulate the effectiveness of immunotherapy. Although this interaction is well documented for immune checkpoint inhibitors, whether this occurs with new experimental compounds has not been evaluated.
A computerized data extraction tool was used to collect clinical data and identify the prescription of a predefined set of medications within 30 days of immunotherapy infusion in the Department of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center. The primary endpoints were median overall survival (OS) and progression-free survival. Tumor responses were assessed using RECIST.
We identified 897 patients. The most prevalent tumor types were colorectal (24.5%), head and neck (10.5%), and pancreatic (9.4%). The immunotherapy administered consisted of monoclonal antibodies and fusion proteins (64.7%), immune modulators (IM; 20.8%), combinations of IMs and antibodies (9.2%), and oncolytic viruses and cancer vaccines (5.3%). The most frequently prescribed drugs were narcotics (70.5%), antiemetics (49.1%), antihistamines (34.6%), antibiotics (31.2%), and proton pump inhibitors (PPI; 28.7%). Patients receiving antihistamines exhibited increased rates of stable disease and partial response (χ2 8.48; P = 0.014) on the IMs and antibodies combination. The benefit of antihistamines was confirmed in a multivariate analysis of OS [HR, 0.752 (95% CI, 0.603-0.938); P = 0.012]. For patients with colorectal cancer, PPI use was associated with shortened survival, with a median OS of 5.2 months with PPI use and 8.6 months without it (P < 0.001).
Our findings highlight the need for strategies to guide concurrent medication choices for patients receiving immunotherapy in early-phase trials.
Concurrent administration of antihistamines correlates with enhanced survival in patients receiving experimental immunotherapy for cancer. Conversely, PPI use diminishes survival in patients with colorectal cancer. These findings highlight how tumor immunogenicity and drug interactions can modulate response and survival outcomes, offering new insights to optimize investigational immunotherapy.
同时使用多种药物可能会调节免疫疗法的疗效。虽然免疫检查点抑制剂的这种相互作用已有充分记录，但新的实验性化合物是否会出现这种情况尚未得到评估。
使用计算机化数据提取工具收集临床数据，并确定德克萨斯大学MD安德森癌症中心肿瘤研究治疗科在免疫疗法输注前30天内预定义的一组药物的处方情况。主要终点为总生存期（OS）和无进展生存期的中位数。使用实体瘤疗效评价标准（RECIST）评估肿瘤反应。
我们共纳入897例患者。最常见的肿瘤类型为结直肠癌（24.5%）、头颈癌（10.5%）和胰腺癌（9.4%）。所给予的免疫疗法包括单克隆抗体和融合蛋白（64.7%）、免疫调节剂（IM；20.8%）、IM与抗体的联合使用（9.2%）以及溶瘤病毒和癌症疫苗（5.3%）。最常开具的药物为麻醉药（70.5%）、止吐药（49.1%）、抗组胺药（34.6%）、抗生素（31.2%）和质子泵抑制剂（PPI；28.7%）。接受抗组胺药治疗的患者在IM与抗体联合使用时疾病稳定和部分缓解的发生率增加（χ2 = 8.48；P = 0.014）。在OS的多因素分析中证实了抗组胺药的益处[风险比（HR），0.752（95%置信区间，0.603 - 0.938）；P = 0.012]。对于结直肠癌患者，使用PPI与生存期缩短相关，使用PPI时的中位OS为5.2个月，未使用时为8.6个月（P < 0.001）。
我们的研究结果强调了在早期试验中需要制定策略来指导接受免疫疗法患者的同时用药选择。
抗组胺药的同时使用与接受实验性癌症免疫疗法患者的生存期延长相关。相反，PPI的使用会降低结直肠癌患者的生存期。这些发现突出了肿瘤免疫原性和药物相互作用如何调节反应和生存结果，为优化实验性免疫疗法提供了新的见解。
