Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jan 2;11(1):e41597.
doi: 10.1016/j.heliyon.2024.e41597. eCollection 2025 Jan 15.

Cancer type-specific adverse events of immune checkpoint inhibitors: A systematic review and meta-analysis

Xuhui Tong  1   2 , Rong Tang  3   4 , Jin Xu  1   2 , Wei Wang  1   2 , Qiong Du  2   5 , Si Shi  3   4 , Xianjun Yu  1   2
Affiliations

Cancer type-specific adverse events of immune checkpoint inhibitors: A systematic review and meta-analysis

Xuhui Tong et al. Heliyon. .

Abstract

Background: The distribution of adverse events (AEs) triggered by immune checkpoint inhibitors (ICIs) across different cancer types has never been demonstrated.

Methods: Randomised controlled trials exclusively assessing ICI monotherapy in cohorts of over 100 patients were considered. Our primary outcome was a comprehensive summary of the distribution of all-grade treatment-related adverse events (TRAEs) as well as serious TRAEs (CTCAE grade 3 or higher) across different malignancies. The study is registered with PROSPERO CRD42023387934.

Findings: 75 trials that enrolled over 100 patients were included. While investigating the incidence of each TRAE across various cancers, we found special linkages existed between certain TRAEs and particular cancer types. In anti-PD-1 monotherapy group, melanoma patients experienced the most frequent fatigue (31.1 %, 95 % CI 29.7%-32.5 %); the incidences of severe pneumonitis and other respiratory disorders were highest in Hodgkin lymphoma (4.1 %, 95 % CI 1.5%-8.6 %; 4.1 %, 95 % CI 1.5%-8.6 %, respectively). Among individuals undergoing single-agent anti-PD-L1, higher frequency of all-grade pruritus occurred in 19.0 % of renal cell carcinoma (RCC) patients (95 % CI 15.2%-23.2 %), and the highest probability of developing other severe musculoskeletal disorders was observed in patients with RCC (6.2 %, 95 % CI 4.0%-9.0 %). In anti-CTLA-4 monotherapy, the incidences of both all-grade and severe diarrhea occurred most frequently in prostate cancer patients (41.9 %, 95 % CI 37.9%-47.9; 14.8 %, 95 % CI 11.5%-18.7 %, respectively).

Interpretation: This is the first comprehensive study addressing the distribution of various TRAEs across cancer types. Our research emphasizes the significance of considering cancer-specific TRAEs when using ICIs for treatment.

PubMed Disclaimer

Conflict of interest statement

The authors declare that there are no conflicts of interest regarding the publication of this manuscript, “Cancer type-specific adverse events of immune checkpoint inhibitors: A systematic review and meta-analysis.” The research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
Incidence rate (95 % CI) of all-grade TRAEs in cancer patients treated with single-agent anti-PD-1.
Fig. 2
Fig. 2
Incidence rate (95 % CI) of all-grade TRAEs in cancer patients treated with single-agent anti-PD-L1.
Fig. 3
Fig. 3
Incidence rate (95 % CI) of all-grade TRAEs in cancer patients treated with single-agent anti-CTLA-4.
Fig. 4
Fig. 4
All-grade TRAEs had a much greater prevalence in specific cancer types. By Figdraw. A. Anti-PD-1 single agent group. B. Anti-PD-L1 single agent group. C. Anti-CTLA-4 single agent group. D. Pie chart of the proportion of patients with different ICI single-agent therapies included in this study.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Postow M.A., Callahan M.K., Wolchok J.D. Immune checkpoint blockade in cancer therapy. J. Clin. Oncol. 2015;33(17):1974–1982. - PMC - PubMed
    1. Bagchi S., Yuan R., Engleman E.G. Immune checkpoint inhibitors for the treatment of cancer: clinical impact and mechanisms of response and resistance. Annu. Rev. Pathol. 2021;16:223–249. - PubMed
    1. Hussaini S., Chehade R., Boldt R.G., Raphael J., Blanchette P., Maleki Vareki S., et al. Association between immune-related side effects and efficacy and benefit of immune checkpoint inhibitors - a systematic review and meta-analysis. Cancer Treat Rev. 2021;92 - PubMed
    1. Gong J., Chehrazi-Raffle A., Reddi S., Salgia R. Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations. J. Immunother. Cancer. 2018;6(1):8. - PMC - PubMed
    1. Yi M., Zheng X., Niu M., Zhu S., Ge H., Wu K. Combination strategies with PD-1/PD-L1 blockade: current advances and future directions. Mol. Cancer. 2022;21(1):28. - PMC - PubMed

LinkOut - more resources