دورية أكاديمية

Immune‐Related Adverse Events and Immune Checkpoint Inhibitor Efficacy in Patients with Gastrointestinal Cancer with Food and Drug Administration‐Approved Indications for Immunotherapy.

التفاصيل البيبلوغرافية
العنوان: Immune‐Related Adverse Events and Immune Checkpoint Inhibitor Efficacy in Patients with Gastrointestinal Cancer with Food and Drug Administration‐Approved Indications for Immunotherapy.
المؤلفون: Das, Satya, Ciombor, Kristen K., Haraldsdottir, Sigurdis, Pumpalova, Yoanna, Sahin, Ibrahim H., Pineda, G., Shyr, Yu, Lin, E.P., Hsu, Chih‐Yuan, Chu, Shih‐Kai, Goff, Laura W., Cardin, Dana B., Bilen, Mehmet A., Fisher, George A., Wu, Christina, Berlin, Jordan
المصدر: Oncologist; Aug2020, Vol. 25 Issue 8, p669-679, 11p, 2 Charts, 4 Graphs
مصطلحات موضوعية: ANTINEOPLASTIC agents, BIOMARKERS, CONFIDENCE intervals, IMMUNE system, IMMUNOTHERAPY, MEDICAL cooperation, RESEARCH, SURVIVAL, GASTROINTESTINAL tumors, PROPORTIONAL hazards models, RETROSPECTIVE studies, DESCRIPTIVE statistics, KAPLAN-Meier estimator, PROGRAMMED cell death 1 receptors, DRUG administration, DRUG dosage
مستخلص: Introduction: Immune‐related adverse event (IRAE) onset may represent a clinical biomarker for anti‐programmed cell death protein 1 (PD‐1) antibody response based on emerging evidence from patients with various advanced malignancies. This phenomenon has not been previously reported in a multidisease cohort of patients with gastrointestinal (GI) cancer with Food and Drug Administration (FDA)‐approved indications to receive immune checkpoint inhibitor therapy. Materials and Methods: The study was a multicenter retrospective cohort analysis of 76 patients with GI cancer who had received anti‐PD‐1 antibodies for FDA‐approved indications. The primary and secondary outcomes of the study were progression‐free survival (PFS) and overall survival (OS) in patients based upon IRAE presence, respectively. PFS and OS were estimated by the Kaplan‐Meier method; a Cox proportional‐hazards model adjusted for IRAE onset, patient age, and enrolling institution was used to analyze outcomes. Results: Median PFS and OS were prolonged in patients who experienced IRAEs compared with those who did not experience them (PFS: not reached [NR] vs. 3.9 months [hazard ratio (HR) 0.13, 95% confidence interval (CI) 0.05–0.3, p <.001]; OS: NR vs. 7.4 months [HR 0.11, 95% CI 0.03–0.36, p <.001]). Among patients who experienced IRAEs, there were no significant differences in PFS and OS by either initial IRAE severity, management, or time to onset. Conclusion: Patients with gastrointestinal cancer who experienced IRAEs while on anti‐PD‐1 antibodies demonstrated significant improvements in PFS and OS compared with their counterparts who did not develop IRAEs. Although these findings add to results from studies in other tumor types, larger prospective studies are needed prior to clinical adoption of IRAE onset as a biomarker for immune checkpoint inhibitor response. Implications for Practice: Predictive clinical biomarkers for immune checkpoint inhibitor response have been understudied in the field of immuno‐oncology. Immune‐related adverse event onset appears to be one such biomarker. Across tumor types, immune‐related adverse event onset has been associated with response to anti‐programmed cell death protein 1 (PD‐1) antibodies. The results of this study demonstrate this for the first time in patients with gastrointestinal cancer receiving anti‐PD‐1 antibodies. Before immune‐related adverse event onset can be adopted clinically as a predictive biomarker for immune checkpoint inhibitor response, however, larger prospective studies are needed to better understand the nuances between immune‐related adverse event characteristics (severity, site, management, timing of onset) and immune checkpoint inhibitor effectiveness. Despite the potential of immune checkpoint inhibitors, few patients with gastrointestinal cancer are eligible to receive these therapeutic agents. The search for biomarkers to better select patients who might respond is ongoing. This article assesses immune‐related adverse events as a possible biomarker in gastrointestinal cancer. [ABSTRACT FROM AUTHOR]
Copyright of Oncologist is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
قاعدة البيانات: Complementary Index
الوصف
تدمد:10837159
DOI:10.1634/theoncologist.2019-0637