Journal
FRONTIERS IN ONCOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2021.667650
Keywords
thyroid dysfunction; PD-1/PD-L1 inhibitors; cancer; meta-analysis; risk
Categories
Funding
- Academic Promotion Program of Shandong First Medical University [2019QL025]
- Natural Science Foundation of Shandong Province [ZR2019MH042]
- Jinan Science and Technology Program [201805064]
- National Science and Technology Major Project of the Ministry of Science and Technology of China [2020ZX09201025]
- Postdoctoral Innovation Project of Jinan
- National Natural Science Foundation of China [81170087]
- Provincial Natural Science Foundation of Shandong [ZR2018MH003]
- Clinical Medical Science and Technology Innovation Program of Jinan [201805004]
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The updated meta-analysis showed that PD-1/PD-L1 inhibitors significantly increase the risk of thyroid dysfunction in cancer patients. Compared with chemotherapy, these inhibitors are particularly prone to causing hypothyroidism, especially when combined with other treatments.
Background: Thyroid dysfunction is common for cancer patients receiving PD-1/PD-L1 inhibitor therapies. To clarify the incidence risk of thyroid dysfunction would be important for guiding anti-PD-1 and anti-PD-L1 immunotherapy. Therefore, the updated meta-analysis was conducted to evaluate the incidence risk of thyroid dysfunction caused by PD-1/PD-L1 inhibitors. Methods: PD-1/PD-L1 inhibitor related clinical trials were collected by a systematic search of the PubMed. Some relevant studies were identified by a manual search. The incidence risk of all grades and grades 3-5 was analyzed and evaluated by random effect model. The Newcastle Ottawa Scale was used for the quality assessment of all clinical trials. Results: Forty-three clinical trials were collected. Compared with chemotherapy, the risk of hypothyroidism of all grades was significantly higher (OR=7.15, 95%CI:[4.85, 10.55], I-2 = 40%, Z=9.91(P < 0.00001)) in PD-1/PD-L1 group. Similar results could also be noted, when the control group was placebo or CTLA-4. When PD-1/PD-L1 was combined with other treatments for cancer patients, the risk of hypothyroidism of all grades was also significantly increased. Similar to the analysis results of hypothyroidism, PD-1/PD-L1 inhibitors played the same role in increasing the risk of hyperthyroidism and thyroiditis. Few significant analysis results was noted, when the risk of thyroid dysfunction of grades 3-5 was assessed. Conclusion: Whether used alone or in combination with other anti-tumor drugs, PD-1/PD-L1 inhibitors increased the risk of thyroid dysfunction, especially for hypothyroidism. Furthermore, PD-1/PD-L1 was better than chemotherapy and CTLA-4 in increasing the risk of thyroid dysfunction.
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