Characteristics and Prognosis of Acquired Resistance to Immune Checkpoint Inhibitors in Gastrointestinal Cancer
Open accessAbstract
Importance: With the expanding use of immune checkpoint inhibitors (ICIs) in gastrointestinal (GI) cancer, the occurrence of acquired resistance (AR) has gradually emerged. However, the progression patterns and survival of patients with AR to ICIs are still unknown. Objective: To explore the characteristics and prognosis of AR after ICI therapy in patients with advanced GI cancer. Design, Setting, and Participants: This cohort study screened patients with advanced GI cancer treated with ICIs between January 14, 2016, and December 31, 2020, at Peking University Cancer Hospital. Initial response was defined as complete response, partial response, or stable disease longer than 6 months as assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Progression was also based on Response Evaluation Criteria in Solid Tumors version 1.1. Progression or death after the initial response was defined as AR. Oligoprogression of AR was defined as 2 or more disease sites progression. The current status of AR in GI cancer and the patterns of AR and its prognosis were evaluated. The site of AR and subsequent management were also assessed. Data were analyzed from June to August 2021. Exposures: Patients in the cohort were treated with mono-ICI or combination therapy. Main Outcomes and Measures: Kaplan-Meier analyses and log-rank tests were conducted for overall survival analyses. Univariate and multivariate Cox analyses were conducted to determine the prognostic implications of each variable. Results: Of the 1124 patients who received ICIs, 373 (33.2%) patients (282 men [75.6%]; median [IQR] age, 62 [54-68] years) achieved an initial response, and 173 (46.4%) patients (137 men [79.2%]; median [IQR] age, 61 [54-67] years) developed AR. Almost all patients (167 patients [96.5%]) developed AR within 24.0 months. Progression patterns of AR were most commonly oligoprogression (122 patients [70.5%]) rather than polymetastatic progression (38 patients [22.0%]) and were associated with a good prognosis (38.5 vs 14.0 months; hazard ratio, 0.37; 95% CI, 0.18-0.74; P < .001). Lymph nodes (101 patients [58.4%]) appeared to be the most common site of AR. Management after AR was mainly systemic therapy (96 patients [55.5%]). Conclusions and Relevance: Oligoprogression was the most common pattern of AR progression, and lymph nodes were the most susceptible site for AR. Further study will be needed to determine the most favorable management for AR.
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Colorectal cancer exhibiting a dMMR/MSI-H profile tends to be located in the right colon and is accompanied by unfavorable characteristics such as distant lymph node metastases, peritoneal cavity spread, mucus secretion, and poor differentiation.
“CRC exhibiting a dMMR/MSI-H profile tends to be located in the right colon, while a constellation of unfavorable characteristics such as distant lymph node metastases, peritoneal cavity spread, mucus secretion, and poor differentiation accompanies it [41,42].”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [42]
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Cites
Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy
Sharma, P., Hu-Lieskovan, S., Wargo, J. A., & Ribas, A. (2017) · Cell · doi:10.1016/j.cell.2017.01.017 · Cited by 5,588 · see citing works
Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma
Zaretsky, J. M., Garcia-Diaz, A., Shin, D. S., Escuin-Ordinas, H., Hugo, W., Hu-Lieskovan, S., Torrejon, D. Y., Abril-Rodriguez, G., Sandoval, S., Barthly, L., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1604958 · Cited by 3,237 · see citing works
Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer
André, T., Shiu, K.-K., Kim, T. W., Jensen, B. V., Jensen, L. H., Punt, C., Smith, D., Garcia-Carbonero, R., Benavides, M., Gibbs, P., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2017699 · Cited by 3,099 · see citing works
Top 10 Challenges in Cancer Immunotherapy
Hegde, P. S., & Chen, D. S. (2020) · Immunity · doi:10.1016/j.immuni.2019.12.011 · Cited by 2,238 · see citing works
Kojima, T., Shah, M. A., Muro, K., François, É., Adenis, A., Hsu, C., Doi, T., Moriwaki, T., Kim, S., Lee, S., et al. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.20.01888 · Cited by 1,122 · see citing works
Self-citationAcquired Resistance to Immune Checkpoint Inhibitors
Schoenfeld, A. J., & Hellmann, M. D. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.03.017 · Cited by 975 · see citing works
Gettinger, S., Choi, J., Hastings, K., Truini, A., Datar, I., Sowell, R., Wurtz, A., Dong, W., Cai, G., Melnick, M. A., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0593 · Cited by 787 · see citing works
Neoantigen landscape dynamics during human melanoma–T cell interactions
Verdegaal, E. M. E., de Miranda, N. F. C. C., Visser, M., Harryvan, T. J., van Buuren, M. M., Andersen, R. S., Hadrup, S. R., van der Minne, C. E., Schotte, R., Spits, H., et al. (2016) · Nature · doi:10.1038/nature18945 · Cited by 464 · see citing works
Enhancing anti-tumour efficacy with immunotherapy combinations
Meric‐Bernstam, F., Larkin, J., Tabernero, J. M., & Bonini, C. (2020) · The Lancet · doi:10.1016/s0140-6736(20)32598-8 · Cited by 412 · see citing works
Xia, L., Liu, Y., & Wang, Y. (2019) · The Oncologist · doi:10.1634/theoncologist.2019-io-s1-s05 · Cited by 393 · see citing works
Self-citationKakavand, H., Jackett, L. A., Menzies, A. M., Gide, T. N., Carlino, M. S., Saw, R. P. M., Thompson, J. F., Wilmott, J. S., Long, G. V., & Scolyer, R. A. (2017) · Modern Pathology · doi:10.1038/modpathol.2017.89 · Cited by 226 · see citing works
Clinical significance of lymph node metastasis in gastric cancer
Deng, J. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i14.3967 · Cited by 198 · see citing works
Human Anti-tumor Immunity: Insights from Immunotherapy Clinical Trials
Egen, J. G., Ouyang, W., & Wu, L. C. (2020) · Immunity · doi:10.1016/j.immuni.2019.12.010 · Cited by 197 · see citing works
da Silva, I. P., Lo, S., Quek, C. Y. J., Gonzalez, M., Carlino, M. S., Long, G. V., & Menzies, A. M. (2019) · Cancer · doi:10.1002/cncr.32522 · Cited by 162 · see citing works
Effects of microsatellite instability on recurrence patterns and outcomes in colorectal cancers
Kim, C. G., Ahn, J. B., Jung, M., Beom, S., Kim, C., Kim, J. H., Heo, S. J., Park, H. S., Kim, J. H., Kim, N. K., et al. (2016) · British Journal of Cancer · doi:10.1038/bjc.2016.161 · Cited by 160 · see citing works
Gettinger, S. N., Wurtz, A., Goldberg, S. B., Rimm, D. L., Schalper, K. A., Kaech, S. M., Kavathas, P., Chiang, A. C., Lilenbaum, R., Zelterman, D. A., et al. (2018) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2018.03.008 · Cited by 135 · see citing works
Current Status and Future Perspective of Immunotherapy in Gastrointestinal Cancers
Lü, Z., Peng, Z., Liu, C. X., Wang, Z., Wang, Y., Jiao, X., Li, J., & Shen, L. (2020) · The Innovation · doi:10.1016/j.xinn.2020.100041 · Cited by 81 · see citing works
Self-citationHagens, E., Henegouwen, M. I. V. B., & Gisbertz, S. S. (2020) · Cancers · doi:10.3390/cancers12061592 · Cited by 75 · see citing works
Lymph Node Metastasis of Gastric Cancer
Akagi, T., Shiraishi, N., & Kitano, S. (2011) · Cancers · doi:10.3390/cancers3022141 · Cited by 66 · see citing works
Pattern of distant metastases in primary extrahepatic bile‐duct cancer: A SEER ‐based study
Wang, X., Yu, G., Chen, M., et al. (2018) · Cancer Medicine · doi:10.1002/cam4.1772 · Cited by 52 · see citing works
Self-citationXu, Y., Li, H., & Fan, Y. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.642883 · Cited by 52 · see citing works
Cannistrà, M., Ruggiero, M., Zullo, A., Serafini, S., Grande, R., & Nardo, B. (2015) · International Journal of Surgery · doi:10.1016/j.ijsu.2015.04.093 · Cited by 38 · see citing works
Heo, J. Y., Yoo, S. H., Suh, K. J., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-81666-x · Cited by 33 · see citing works
Zuo, C., Xie, H., Liu, J., et al. (2014) · Molecular and Clinical Oncology · doi:10.3892/mco.2014.303 · Cited by 31 · see citing works
Moehler, M. H., Janjigian, Y. Y., Adenis, A., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2018.36.4_suppl.tps192 · Cited by 30 · see citing works
Tykodi, S. S., Donskov, F. N., Lee, J., et al. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.2019.37.15_suppl.4570 · Cited by 17 · see citing works
Acquired resistance to PD-1 blockade in NSCLC.
Schoenfeld, A. J., Rizvi, H. A., Memon, D., et al. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.2020.38.15_suppl.9621 · Cited by 17 · see citing works
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Borelli, B., Antoniotti, C., Carullo, M., Germani, M. M., Conca, V., & Masi, G. (2022) · Cancers · doi:10.3390/cancers14204974 · Cited by 62 · see citing works
Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy
Nikolouzakis, T. K., Chrysos, E., Docea, A. O., Fragkiadaki, P., Souglakos, J., Tsiaoussis, J., & Tsatsakis, A. (2024) · Cancers · doi:10.3390/cancers16111995 · Cited by 37 · see citing works
- Authors
- Zhuo, N., Liu, C., Zhang, Q., Li, J., Zhang, X., Gong, J., Lu, M., Peng, Z., Zhou, J., Wang, X., Jiao, X., Wang, Y., Wang, Y., Gao, M., Shen, L., & Lu, Z.
- Affiliations
- Peking University Cancer Hospital (CN)
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China
- Corresponding author
- Shen, Lin
- ORCID
- Venue
- JAMA Network Open
- Publisher
- American Medical Association (AMA)
- Published
- 2022-03-29
- Volume
- 5
- Issue
- 3
- Pages
- e224637
- ISSN
- 2574-3805 (ISSN-L)
- PMC
- PMC8965636
- OpenAlex
- W4220772877
- Cited by
- 30
- References
- 28
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 9 · 2023: 2 · 2022: 3
- FWCI
- 2.61
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- JAMA Network Open (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Keywords
- acquired resistance, immune checkpoint inhibitors, gastrointestinal cancer, oligoprogression, progression patterns, prognosis, overall survival, immune-related adverse events, immune-related pneumonitis, immune-related colitis, immune-related endocrinopathy, immune-related encephalitis, immune-related dermatitis, immune-related hypophysitis, immune-related hepatitis, immune-related nephritis
- MeSH terms
- Immune Checkpoint Inhibitors, Female, Gastrointestinal Neoplasms, Humans, Male, Middle Aged, Prognosis, Cohort Studies, Survival Analysis
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