NCCN 2025丨刘继红教授：加强管理，注意免疫联合化疗治疗子宫内膜癌的不良事件

Meta-Analysis of Randomized Controlled Trials (RCTs) to Evaluate the Incidence of Venous Thromboembolism (VTE) and Immune-Related Adverse Events (iRAEs) in Patients with Primary Advanced or Recurrent Endometrial Cancer Treated with Immunochemotherapy

INTRODUCTION:

Immunochemotherapy, combining immune checkpoint inhibitors (ICIs) with platinum-based chemotherapy, has demonstrated improved survival and durable treatment responses for patients with primary advanced or recurrent endometrial cancer (EC). While enhancing treatment efficacy, immunochemotherapy also raises concerns about adverse events, specifically hypothyroidism, rash/dermatitis, and venous thromboembolism (VTE). This meta-analysis evaluates the incidence and relative risk of iRAEs(hypothyroidism and rash/dermatitis) and VTE in patients with primary advanced or recurrent EC treated with immunochemotherapy compared to chemotherapy alone.

METHOD:

Literature Search:

We conducted a comprehensive literature search using Medline, Embase, and Cochrane databases from inception through August 10th, 2024.

Eligibility Criteria:

Eligible studies included Phase II/III RCTs utilizing immunochemotherapy in primary advanced or recurrent EC reporting hypothyroidism, rash/dermatitis, and VTE (deep vein thrombosis and/or pulmonary embolism) events.

Data Extraction:

Data extraction was independently conducted by two authors; discrepancies were resolved by a third reviewer.

Study Outcome Measures:

The primary endpoint of our meta-analysis was the incidence of hypothyroidism, rash/dermatitis, and VTE (deep vein thrombosis and/or pulmonary embolism) events.

Data Synthesis and Analysis. The primary meta-analytic approach was a random effects model using the Mantel-Haenszel (MH) method. This method was used to calculate the estimated pooled risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CI). Heterogeneity among the studies was assessed using the I2 statistic and Cochran’s Q-statistic. A p-value of less than 0.05 was considered statistically significant.

RESULTS:

Search Results:

A total of 2624 patients from four Phase III RCTs (AtTEnd, NRG-GY018, RUBY, DUO-E) and one phase II RCT (MITO END-3) were eligible for evaluation of hypothyroidism, rash/dermatitis, and VTE, events.

Characteristics of the Studies:

All five trials compared immunotherapy combined with chemotherapy versus placebo plus chemotherapy in primary advanced or recurrent EC.

Meta-Analysis Results:

The incidence of hypothyroidism was 12.53% in the immunochemotherapy arm vs 3.61% in the control arm (RR 3.27; 95% CI: 2.34-4.57; P < 0.00001). The incidence of rash/dermatitis was 12.07% in the immunochemotherapy arm vs 6.85% in the control arm (RR 1.80; 95% CI: 1.39-2.33; P < 0.00001). The incidence of VTE was not statistically significant. 3.56% in the immunochemotherapy arm vs 2.07% in the control arm (RR 1.60; 95% CI: 0.97-2.64; P = 0.07).

CONCLUSIONS:

Patients with primary advanced or recurrent endometrial cancer treated with immunochemotherapy had a significantly higher incidence of hypothyroidism and rash/dermatitis compared to chemotherapy alone, emphasizing the need for proactive monitoring and management of these immune-related adverse events. While the incidence of venous thromboembolism was higher in the immunochemotherapy group, the difference was not statistically significant, suggesting further studies are needed to confirm this trend. The findings underscore the importance of balancing the therapeutic benefits of immunochemotherapy with its potential risks, reinforcing the need for personalized treatment strategies and vigilant adverse event management to optimize patient outcomes.