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. 2021 Jun 18:12:700007.
doi: 10.3389/fneur.2021.700007. eCollection 2021.

Clinical Efficacy of Temozolomide and Its Predictors in Aggressive Pituitary Tumors and Pituitary Carcinomas: A Systematic Review and Meta-Analysis

Mei Luo  1 , Yiheng Tan  1 , Wenli Chen  1 , Bin Hu  1 , Zongming Wang  1 , Diming Zhu  1 , Haosen Jiao  1 , Chengbin Duan  1 , Yonghong Zhu  2 , Haijun Wang  1
Affiliations

Clinical Efficacy of Temozolomide and Its Predictors in Aggressive Pituitary Tumors and Pituitary Carcinomas: A Systematic Review and Meta-Analysis

Mei Luo et al. Front Neurol. .

Abstract

Background: A growing number of evidences suggest that TMZ applications can generate impressive benefits for APT and PC patients. However, the definite role of TMZ for individuals remains unclarified due to the variation between studies. And the predictive factors to alter its efficacy remain debatable. Objective: To evaluate the long-term effectiveness and safety profile of TMZ in the treatment of pituitary malignancies, and delineate the predictors during its clinical employment. Results: A literature retrieval was conducted from online databases for studies published up to December 31, 2020. Twenty one studies involving 429 patients were identified. TMZ exhibited 41% radiological overall response rate (rORR). The biochemical response rate was determinate in 53% of the functioning subset. Two-year and 4-year survival rate were 79 and 61%, respectively. TMZ prolonged the median PFS and OS as 20.18 and 40.24 months. TMZ-related adverse events occurred in 19% of patients. Regarding predictors of TMZ response, rORR was dramatically improved in patients with low/intermediate MGMT expression than those with high-MGMT (>50%) (p < 0.001). The benefit of TMZ varied according to functioning subtype of patients, with greater antitumor activities in functioning subgroups and fewer activities in non-functioning sets (p < 0.001). Notably, the concomitant therapy of radiotherapy and TMZ significantly increased the rORR (p = 0.007). Conclusion: TMZ elicits clinical benefits with moderate adverse events in APT and PC patients. MGMT expression and clinical subtype of secreting function might be vital predictors of TMZ efficacy. In the future, the combination of radiotherapy with TMZ may further improve the clinical outcomes than TMZ monotherapy.

Keywords: aggressive pituitary tumors; meta-analysis; pituitary adenoma; pituitary carcinomas; temozolomide.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Algorithm of literature retrieval and study selection.
Figure 2
Figure 2
Responsive and survival outcomes of TMZ in APT and PC patients. (A) Radiological overall response rate was achieved in 41% of patients. (B) 53% of patients were biochemically responsive to TMZ. (C,D) 2-year survival rate was 79% and 4-year survival rate was 61%. (E,F) Median PFS and OS were 20.18 months and median OS was 40.24 months, respectively.
Figure 3
Figure 3
Occurrence of TMZ-related adverse events.
Figure 4
Figure 4
The correlation between MGMT expression level and TMZ radiological response. (A) Radiological response rate was 57% in patients with minimal-MGMT expression, 47% in patients with intermediate-MGMT expression, and 5% in patients with high-MGMT expression. (B) Radiological response rate was spectacularly lower in APT and PC patients with high-MGMT expression than those with minimal and intermediate-MGMT expression group in the quantitative histogram. ***P < 0.001.
Figure 5
Figure 5
The correlation between MGMT promoter methylation status and TMZ radiological response. (A) Radiological response rate was 54% in the MGMT promoter methylated group, and 30% in the unmethylated group. (B) The quantitative histogram showed the difference between groups was not significant.
Figure 6
Figure 6
Relationship between clinical functioning subtype and radiological response of TMZ in patients with APT and PC. (A) 43% radiological response rate to TMZ presented in the functioning subset, and non-functioning specimens only 20% radiological response. (B) The difference between groups was not dramatic as shown in the quantitative histogram. ***P < 0.001.
Figure 7
Figure 7
Radiological response after concomitant application of radiotherapy and TMZ for patients with APT and PC. (A) Concomitant application of radiotherapy and TMZ generated 60% radiological response, and TMZ monotherapy elicited a 37% radiological response. (B) Quantitative histogram showed the combined therapy significantly increased the radiological response than TMZ monotherapy. ***P < 0.001.
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