The Risk of Immune-Related Thyroid Dysfunction Induced by PD-1/PD-L1 Inhibitors in Cancer Patients: An Updated Systematic Review and Meta-Analysis

Abstract

BackgroundThyroid 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.MethodsPD-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.ResultsForty-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], I2 = 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.ConclusionWhether 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.

Challenges and Limitations of Endocrine Toxicity Evaluation in Non-Small Cell Lung Cancer Patients Treated with Immunotherapy—Retrospective Study from a Tertiary-Level Hospital in Romania

“…In daily clinical practice, referral to endocrinology evaluation is elective. As endocrine irAEs have been reported in randomized clinical trials [33][34][35][36][37][38] and in updated systematic reviews and meta-analyses [39,40], ESMO guidelines recommend TFT at the baseline every 4-6 weeks during treatment, as well as 4-6 weeks after the last cycle [9].…”

Tumor-Associated Macrophages: Key Players in Triple-Negative Breast Cancer

“…It can also activates Treg cells and helper T cells causing tumor immunosuppression (50-58) (Figure 1). As a regulatory factor which limits killing effect of T cells, PD-1 is widely present in a variety of T cells (59)(60)(61)(62)(63). PD-L1 is the receptor of PD-1, which is mostly expressed on the surface of tumor cells and macrophages (61,(64)(65)(66).…”

“…As a regulatory factor which limits killing effect of T cells, PD-1 is widely present in a variety of T cells ( 59 – 63 ). PD-L1 is the receptor of PD-1, which is mostly expressed on the surface of tumor cells and macrophages ( 61 , 64 – 66 ).…”

Future of epigenetic immunotherapy in kidney cancer

“…Однако при этом наблюдалась значительная частота развития серьезных побочных эффектов III степени -75,8 % у пациентов, получающих пермбролизумаб с акситинибом [13]. Метаанализы результатов лечения различных ЗНО показали, что применение ингибиторов PD-L1 и PD-1 в монорежиме или в комбинации с другими противоопухолевыми препаратами достоверно повышает риск токсического поражения печени [14], иммунозависимого пневмонита [15], дисфункции щитовидной железы (особенно гипотиреоза) [16] и сыпи (особенно при комбинации анти-PD-L1 и анти-PD-1) [17]. Метаанализ результатов применения анти-PD-L1/PD-1 в монорежиме у пациентов старше 75 лет для лечения ПКК и других солидных опухолей не показал их эффективности [18].…”