- Lung and Thoracic cancer
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Association of Immune-Related Adverse Events and the Efficacy of Anti–PD-(L)1 Monotherapy in Non–Small Cell Lung Cancer: Adjusting for Immortal-Time Bias
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Ying Yu, Ning Chen, Sizhe Yu, Wanji Shen, Wanchen Zhai, Hui Li, Yun Fan
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Cancer Res Treat. 2024;56(3):751-764. Published online January 2, 2024
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DOI: https://doi.org/10.4143/crt.2023.1118
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 Abstract
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- Purpose
The association between immune-related adverse events (irAEs) and survival outcomes in non–small cell lung cancer (NSCLC) patients treated with programmed death-(ligand) 1 [PD-(L)1] inhibitors remains controversial, partly due to variations in dealing with immortal-time bias (ITB).
Materials and Methods
We retrospectively enrolled 425 advanced NSCLC patients who received anti–PD-(L)1 monotherapy between January 2016 and June 2021, stratifying them into irAE (n=127) and non-irAE (n=298) groups. The primary endpoint was to assess the impact of irAEs on progression-free survival (PFS) and overall survival (OS). Landmark (2-, 3-, 6-, and 9-month) and time-dependent Cox analyses were performed to eliminate ITB.
Results
With a median follow-up of 38.8 months, the occurrence of overall irAEs was significantly associated with superior PFS (11.2 vs. 3.4 months, p < 0.001) and OS (31.4 vs. 14.0 months, p < 0.001), which persisted in landmark and time-dependent Cox analyses. For the main organ-specific irAEs, skin, thyroid, and hepatic irAEs, respectively, showed significantly improved survival compared to the non-irAE group, whereas pneumonitis did not. Single-organ irAEs had the best outcomes compared with multi-organ or no irAE, which also held across subgroups of skin, thyroid, and hepatic irAEs. Moreover, severe grade irAEs and immunotherapy discontinuation had a detrimental effect on survival, systemic steroid therapy showed little effect, while immunotherapy resumption had tolerable safety and a trend of improved survival.
Conclusion
After adequately adjusting ITB, the occurrence of overall irAEs predicts for favorable efficacy of anti–PD-(L)1 monotherapy in NSCLC, with better outcomes observed in patients with skin, thyroid, or hepatic irAEs, particularly those with single-organ involvement.
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Citations
Citations to this article as recorded by  - Development of pituitary dysfunction and destructive thyroiditis is associated with better survival in non-small cell lung cancer patients treated with programmed cell death-1 inhibitors: a prospective study with immortal time bias correction
Koji Suzuki, Tomoko Kobayashi, Tetsushi Izuchi, Koki Otake, Masahiko Ando, Tomoko Handa, Takashi Miyata, Mariko Sugiyama, Takeshi Onoue, Daisuke Hagiwara, Hidetaka Suga, Ryoichi Banno, Tetsunari Hase, Megumi Inoue, Makoto Ishii, Hiroshi Arima, Shintaro Iw
Frontiers in Endocrinology.2024;[Epub] CrossRef - Associations between Immune-related Adverse Events and Prognosis in Cancer Patients Receiving Immune Checkpoint Inhibitor Therapy
Yusuke Inoue, Naoki Inui
Internal Medicine.2024;[Epub] CrossRef
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