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Prognostic Significance of the Severity of Immune-Related Adverse Events in Advanced Cancer Patients Treated with PD-1/PD-L1 Inhibitors: A Real-World Data Analysis

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Abstract

Background

There is limited evidence regarding immune-related adverse events (irAEs) in Asian cancer patients treated with antibodies directed against programmed cell death-1 (PD-1) or programmed cell death-ligand 1 (PD-L1).

Objective

This study aimed to investigate the clinical patterns and prognostic significance of grade 1–2 and grade ≥ 3 irAEs by PD-1/PD-L1 inhibitors in cancer patients using real-world clinical data.

Patients and Methods

We conducted a retrospective study of cancer patients who received pembrolizumab, nivolumab, or atezolizumab at a tertiary hospital in South Korea. Incidence, time to onset, and grade 1–2 and grade ≥ 3 irAE risk factors were analyzed from medical records. The association of irAE severity with progression-free survival (PFS) and prognostic factors for PFS were evaluated.

Results

Among a total of 431 patients, irAEs occurred in 45.2%, and 9.5% were grade ≥ 3 irAEs. There were no significant differences in the median time to onset based on severity. Risk factors for the development of grade ≥ 3 irAEs were the presence of autoimmune disorders or diabetes mellitus. The median PFS was significantly different at 13.20, 9.00 and 4.17 months for the grade 1–2, grade ≥ 3, and no irAE groups, respectively. An increase in administration cycles was associated with a reduced risk of progression in patients with grade 1–2 and grade ≥ 3 irAEs.

Conclusions

The development of grade ≥ 3 irAEs was affected by comorbidities and associated with improved PFS compared with those without irAEs. Our findings identified the real-world epidemiology, risk factors, and prognostic significance of irAEs, which may guide treatment decisions of PD-1/PD-L1 inhibitors.

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Author notes

  1. Su Jeong Song and Yun-Kyoung Song equally contributed to the manuscript.

Authors and Affiliations

  1. Department of Pharmacy, Seoul National University Hospital, Seoul, Republic of Korea

    Su Jeong Song, Eunjeong Shin, Sung Yun Suh & Yoon Sook Cho

  2. College of Pharmacy, Daegu Catholic University, Gyeongsan-si, Gyeongbuk, Republic of Korea

    Yun-Kyoung Song

  3. Department of Pharmacy, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea

    Mihwa Jang

  4. Department of Pharmacy, Sheikh Khalifa Specialty Hospital, Ras Al Khaimah, United Arab Emirates

    Eunjeong Shin

  5. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea

    Ju-Yeun Lee & Jung Mi Oh

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Correspondence to Jung Mi Oh.

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Funding

This research was supported by a Grant (22183MFDS499) from the Ministry of Food and Drug Safety in 2022.

Conflicts of interest

Su Jeong Song, Yun-Kyoung Song, Mihwa Jang, Eunjeong Shin, Sung Yun Suh, Yoon Sook Cho, Ju-Yeun Lee, and Jung Mi Oh declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

Availability of data and material

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. The data are not publicly available due to privacy or ethical restrictions.

Ethics approval

This retrospective chart review study involving human participants was in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by the Institutional Review Board of the SNUH (IRB No. 1903-135-1020, April 1, 2019).

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Informed consent was waived due to the retrospective design of the study.

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Author contributions

SJS: conceptualization, data curation, formal analysis, methodology, project administration, writing—original draft; Y-KS: conceptualization, formal analysis, software; validation; visualization; writing—original draft; MJ: investigation, formal analysis; EJS: resources, writing—review & editing; SYS: resources, writing—review & editing; YSC: resources, writing—review & editing; J-YL: conceptualization, methodology, writing—review & editing; JMO: conceptualization; funding acquisition; methodology; supervision; writing—review & editing. All authors read and approved the final manuscript.

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Song, S.J., Song, YK., Jang, M. et al. Prognostic Significance of the Severity of Immune-Related Adverse Events in Advanced Cancer Patients Treated with PD-1/PD-L1 Inhibitors: A Real-World Data Analysis. Targ Oncol 18, 147–158 (2023). https://doi.org/10.1007/s11523-022-00936-4

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