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Immune checkpoint inhibitors (ICIs) in gastrointestinal (GI) cancer: Immune-related adverse events (IRAEs) and efficacy.
Abstract
4116 Background: Despite the therapeutic promise of ICIs for patients (pts) with some advanced malignancies, they are FDA-approved for only a few GI cancer pts. In NSCLC, melanoma and urothelial carcinoma, there is emerging data that pts who experience IRAEs while on ICIs have improved outcomes compared with pts who do not. This association in GI cancer pts has not been reported. Methods: We retrospectively analyzed outcomes for metastatic GI cancer pts receiving ICIs for FDA-approved indications (later-line MSI-H tumors, 2 nd line hepatocellular carcinoma (HCC), 3 rd line PD-L1+ gastric (GA)/gastroesophageal junction (GEJ) adenocarcinoma), at Vanderbilt Ingram Cancer Center, Winship Cancer Institute and Stanford Cancer Institute. Our primary aim was to compare progression-free survival (PFS) and overall survival (OS) between pts who did and did not experience IRAEs. Secondary aims were comparison of these outcomes within pts who experienced IRAEs, by initial IRAE severity (Grade (G)3/G4 vs G1/G2) (CTCAE v5.0), time-to-onset (TTO) (≤ 6 weeks (w) vs > 6 w) and management (steroids vs drug cessation vs observation). PFS and OS were determined by Kaplan-Meier (KM) analysis; KM comparisons were done by the logrank test. Results: Between 1/2015-12/2018 61 GI cancer pts with HCC (28), colorectal cancer (27) and GA/GEJ cancer (6) were treated with ICIs; median age was 63 years. The majority (59) received single-agent nivolumab or pembrolizumab while minority (2) received nivolumab and ipilimumab; median time on ICIs was 5.9 months (mos). Twenty-four pts experienced initial IRAEs (6 G3/G4, 18 G1/G2); median TTO was 3.8 mos. Pts who experienced any IRAE had improvements in PFS and OS compared to those who did not (PFS: 32.4 mos (95% confidence interval (CI), 32.4-not reached (NR)) vs 4.8 mos (95% CI, 2.9-8.7), p = 0.0001; OS: 32.4 mos (95% CI, 32.4-NR) vs 8.5 mos (95% CI, 6-NR), p = 0.0036). Among pts who experienced IRAEs, PFS and OS differences between above-specified subgroups did not meet statistical significance. Conclusions: GI cancer pts who experienced IRAEs while on ICIs had marked improvements in PFS and OS compared to those who did not, suggesting the predictive potential for IRAEs as a clinical biomarker in this population.
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In that analysis, patients who experienced IRAEs had a prolonged OS compared to those who did not (32.4 vs 8.5 months, p = .0036).
“OS: 32.4 vs 8.5 months, p = .0036”
From Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors (2019) · cites this paper as [42]
In a retrospective analysis of 61 gastrointestinal cancer patients, 39.3% experienced IRAEs.
“Of included patients, 39.3% experienced IRAEs with the most common sites being musculoskeletal (29.4%), dermatologic (26.5%) and endocrine (20.6%).”
From Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors (2019) · cites this paper as [42]
In that analysis, no statistically significant differences in PFS and OS were found in patients who experienced IRAEs based upon IRAE severity, management and timing of onset.
“No statistically significant differences in PFS and OS were found in patients who experienced IRAEs based upon IRAE severity, management and timing of onset.”
From Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors (2019) · cites this paper as [42]
In that analysis, patients who experienced IRAEs had a prolonged PFS compared to those who did not (32.4 vs 4.8 months, p = .0001).
“PFS: 32.4 vs 4.8 months, p = .0001”
From Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors (2019) · cites this paper as [42]
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Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors
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Self-citationIranzo, P., Callejo, A., Assaf, J. D., Molina, G., López-Valbuena, D., García-Illescas, D., Pardo, N., Navarro, A., Martínez‐Martí, A., Cedrés, S., et al. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.875974 · Cited by 102
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“Similarly, irAE severity has not affected treatment efficacy outcomes in several studies [58].”
Fiala, O., Šorejs, O., Šustr, J., Kučera, R., Topolčan, O., & Fínek, J. (2020) · Anticancer Research · doi:10.21873/anticanres.14063 · Cited by 34
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“Two retrospective studies, one of NSCLC and one of gastrointestinal cancers likewise demonstrated improved OS and PFS in patients on anti-PD-1 who experienced irAEs [69,74].”
Yu, K. (2022) · Annals of Gastroenterology · doi:10.20524/aog.2022.0742 · Cited by 4
Pellitero, A. M., García, M. Z., Ruiz, M. G., Arbonés-Mainar, J. M., del Prado, R. L., & Isla, D. (2024) · World Journal of Oncology · doi:10.14740/wjon1790 · Cited by 3
“…may be predictive of anti-PD-1 and anti-PD-L1 antibody responses in a wide variety of solid tumors, including NSCLC [5], first-or second-line renal cell carcinoma [6], locally advanced or metastatic urothelial carcinoma [7], certain gastrointestinal (GI) tumors [8], and head and neck tumors [9].”
BackgroundHow to manage side effects of immunotherapy
Kopecký, J., & Kubeček, O. (2020) · Onkologie · doi:10.36290/xon.2020.049 · Cited by 2
“To platí pro nádory ledvin (29, 30), uroteliální karcinom (20), gastrointestinálními tumory (31) nebo nádory hlavy a krku (32).”
Rabeau, A., Lavesque, J., Joseph, C., Cortot, A. B., & Mazières, J. (2021) · Revue des Maladies Respiratoires Actualités · doi:10.1016/s1877-1203(21)00108-7
Sakurai, K., Imaue, S., Ikeda, A., Sakurai, A., Tachinami, H., Takatsuka, D., Fujiki, M., & Yamada, S. (2025) · Journal of Oral and Maxillofacial Surgery Medicine and Pathology · doi:10.1016/j.ajoms.2025.09.015
Metadata
- Authors
- Das, S., Ciombor, K. K., Haraldsdottir, S., Pumpalova, Y. S., Sahin, I. H., Shyr, Y., Chu, S.-K., Lin, E. P.-Y., Hsu, C.-Y., Goff, L. W., Cardin, D. B., Bilen, M. A., Berlin, J., & Wu, C.
- Affiliations
- Vanderbilt University Medical Center (US)
- Stanford University, Stanford, CA;
- Stanford University (US)
- 1574, Atlanta, GA;
- Vanderbilt University (US)
- Emory University Winship Cancer Institute, Atlanta, GA;
- The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (US)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2019-05-20
- Volume
- 37
- Issue
- 15_suppl
- Pages
- 4116-4116
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2947232061
- Cited by
- 15
- References
- 0
- Citations by year
- 2025: 2 · 2024: 2 · 2022: 3 · 2021: 2 · 2020: 4 · 2019: 2
- Type
- conference abstract
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- 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 checkpoint inhibitors, immune-related adverse events, gastrointestinal cancer, hepatocellular carcinoma, gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, colorectal cancer, nivolumab, pembrolizumab, ipilimumab, progression-free survival, overall survival, immune-related pneumonitis, immune-related colitis, immune-related endocrinopathy
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