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Safety profile of EZH2 inhibitors for cancer: a systematic review and meta-analysis
Zhou Zhao1,2, Xiufeng Chen3, Huayang Pang3
1Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, China.
Objective:
To evaluate the safety profiles of EZH2-targeted inhibitors in cancer treatment, focusing on treatment-related adverse events (TRAEs) across various clinical trials.
Methods:
We conducted a systematic review and meta-analysis using data from clinical trials involving EZH2 inhibitors reported up to May 31, 2024. Databases searched included PubMed, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), and ClinicalTrials.gov. Studies included were those involving patients treated with EZH2 inhibitors as monotherapy or in combination, specifically detailing the incidence of TRAEs. Data on all-grade TRAEs, grade 3 or higher TRAEs, and severe TRAEs were extracted and analyzed using random-effects models.
Results:
Our systematic review and meta-analysis included 22 studies encompassing 1,002 patients who met the inclusion criteria. TRAEs were commonly observed during EZH2 inhibitor therapy, affecting 86% of patients (95% CI [79-94%]%; I2 = 89.5%). The incidence of grade 3 or higher TRAEs was 33% (95% CI [21-44%]; I2 = 93.5%), while severe TRAEs occurred in 15% of the cases (95% CI [9-22%]; I2 = 87.5%). The most frequently reported grade 3 or higher TRAEs in the pooled analysis were neutropenia (8%), thrombocytopenia (8%), and anemia (6%). Specifically, for tazemetostat, the most common grade 3 or higher TRAE was neutropenia (5%). For SHR2554, the most prevalent grade 3 or higher TRAEs were thrombocytopenia (17%), neutropenia (8%), and anemia (7%). Notably, treatment-related fatalities were rare, with only 0.9% of patients experiencing potentially fatal outcomes due to therapy.
Conclusion:
EZH2 inhibitors demonstrate a manageable safety profile with a low incidence of severe TRAEs, emphasizing their potential as safe therapeutic options in cancer treatment. The low rate of severe TRAEs and the rare occurrences of treatment-related deaths support the continued clinical use and further investigation of EZH2 inhibitors.
Insights
EZH2 inhibitors show a manageable safety profile in cancer treatment, with most treatment-related adverse events (TRAEs) being mild. Severe TRAEs and fatalities are rare, supporting their continued clinical use.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Enhancer of Zeste Homolog 2 (EZH2) is a key epigenetic regulator implicated in various cancers.
- Targeting EZH2 offers a promising therapeutic strategy for cancer treatment.
- Understanding the safety profile of EZH2 inhibitors is crucial for their clinical application.
Purpose of the Study:
- To systematically evaluate the safety profiles of EZH2-targeted inhibitors in cancer treatment.
- To focus on the incidence and types of treatment-related adverse events (TRAEs) across clinical trials.
- To assess the overall safety and tolerability of EZH2 inhibitors.
Main Methods:
- A systematic review and meta-analysis of clinical trials involving EZH2 inhibitors.
- Data extraction from studies reported up to May 31, 2024, including PubMed, Embase, CENTRAL, and ClinicalTrials.gov.
- Analysis of all-grade, grade 3 or higher, and severe TRAEs using random-effects models.
Main Results:
- 22 studies with 1,002 patients were included. 86% experienced TRAEs, with 33% having grade 3 or higher events.
- The most common grade 3+ TRAEs were neutropenia (8%), thrombocytopenia (8%), and anemia (6%).
- Severe TRAEs occurred in 15% of patients, and treatment-related fatalities were rare (0.9%).
Conclusions:
- EZH2 inhibitors exhibit a manageable safety profile in cancer therapy.
- The incidence of severe TRAEs is low, supporting their potential as safe therapeutic options.
- Continued clinical use and further investigation of EZH2 inhibitors are warranted.
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