Immune-Related Adverse Events and Immune Checkpoint Inhibitor Efficacy in Patients with Gastrointestinal Cancer with Food and Drug Administration-Approved Indications for Immunotherapy
Open accessAbstract
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.
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Patients with any-grade irAEs had better PFS.
“As in previous reports29–31, landmark analysis (landmark time point for OS set at 10 months after therapy initiation) identified that any-grade irAEs were associated with improved PFS (Supplementary Table 6 and Supplementary Fig. 4a).”
From Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1 (2022) · cites this paper as [29]
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- Authors
- Das, S., Ciombor, K. K., Haraldsdottir, S., Pumpalova, Y., Sahin, I. H., Pineda, G., Shyr, Y., Lin, E. P., Hsu, C.-Y., Chu, S.-K., Goff, L. W., Cardin, D. B., Bilen, M. A., Fisher, G. A., Wu, C., & Berlin, J.
- Affiliations
- Vanderbilt University Medical Center (US)
- Divisions of Medical Oncology, Department of Medicine, Stanford University Medical Center, Stanford, California, USA
- Stanford Medicine (US)
- Department of Hematology and Medical Oncology, Emory University, Atlanta, Georgia, USA
- Fu Jen Catholic University (TW)
- Emory University (US)
- Corresponding author
- Das, Satya
- ORCID
- Venue
- The Oncologist
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-01-14
- Volume
- 25
- Issue
- 8
- Pages
- 669-679
- ISSN
- 1083-7159 (ISSN-L)
- 1549-490X
- PMC
- PMC7418359
- OpenAlex
- W3004284786
- Cited by
- 41
- References
- 33
- Citations by year
- 2025: 6 · 2024: 6 · 2023: 8 · 2022: 11 · 2021: 6 · 2020: 4
- FWCI
- 2.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- The Oncologist (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- VCORCDP (5 K12 CA90625-19)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- immune-related adverse events, immune checkpoint inhibitors, anti-PD-1, gastrointestinal cancer, predictive biomarkers, immune checkpoint inhibitor response, progression-free survival, overall survival, immunotherapy response biomarkers
- MeSH terms
- Immune Checkpoint Inhibitors, Gastrointestinal Neoplasms, Humans, Immunotherapy, Prospective Studies, Retrospective Studies, United States, United States Food and Drug Administration
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