Aggressive pituitary tumors and carcinomas: medical treatment beyond temozolomide.

IF 2.5 Q3 ENDOCRINOLOGY & METABOLISM
Dario DE Alcubierre, Anna L Carretti, François Ducray, Emmanuel Jouanneau, Gérald Raverot, Mirela D Ilie
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Abstract

Aggressive pituitary tumors are a subset of pituitary neoplasms, characterized by unusually fast growth rate, invasiveness and overall resistance to optimized standard treatment. When metastases are present, the term pituitary carcinoma is employed. After failure of standard treatments, current guidelines recommend first-line temozolomide monotherapy. However, a significant number of patients do not respond to temozolomide, or experience disease progression following its discontinuation; in these latter cases, re-challenge with temozolomide is generally advised, although the reported outcomes have been less satisfactory. Although no alternative therapies have been formally recommended after temozolomide failure, growing evidence regarding potential second- or third-line therapeutic strategies has emerged. In the present work, we reviewed the available evidence published up to April 2023 involving the most relevant therapies employed so far, namely immune checkpoint inhibitors, bevacizumab, peptide radionuclide receptor therapy, tyrosine kinase inhibitors and mTOR inhibitors. For each treatment, we report efficacy and safety outcomes, along with data regarding potential predictors of response. Overall, immune checkpoint inhibitors and bevacizumab are showing the most promise as therapeutic options after temozolomide failure. The former showed better responses in pituitary carcinomas. Peptide radionuclide receptor therapy has also showed some efficacy in these tumors, while tyrosine kinase inhibitors and mTOR inhibitors have exhibited so far limited or no efficacy. Further studies, as well as an individualized, patient-tailored approach, are clearly needed. In addition, we report an unpublished case of a silent corticotroph pituitary carcinoma that progressed under dual immunotherapy, and then showed stable disease under a combination of lomustine and bevacizumab.

侵袭性垂体瘤和癌:替莫唑胺以外的药物治疗。
侵袭性垂体瘤是垂体肿瘤的一个分支,其特点是生长速度异常快、侵袭性强以及对优化标准治疗的整体抵抗力。当出现转移时,则称为垂体癌。标准治疗失败后,目前的指南建议采用替莫唑胺单药一线治疗。然而,有相当多的患者对替莫唑胺无反应,或在停药后病情出现进展;在后一种情况下,一般会建议患者再次接受替莫唑胺治疗,但报告的结果并不令人满意。尽管在替莫唑胺治疗失败后还没有正式推荐替代疗法,但已有越来越多的证据表明可能存在二线或三线治疗策略。在本研究中,我们回顾了截至 2023 年 4 月发表的现有证据,涉及迄今为止采用的最相关疗法,即免疫检查点抑制剂、贝伐珠单抗、肽放射性核素受体疗法、酪氨酸激酶抑制剂和 mTOR 抑制剂。我们报告了每种疗法的疗效和安全性结果,以及有关潜在反应预测因素的数据。总体而言,免疫检查点抑制剂和贝伐单抗最有希望成为替莫唑胺治疗失败后的治疗选择。前者对垂体癌的反应更好。肽放射性核素受体疗法对这些肿瘤也有一定疗效,而酪氨酸激酶抑制剂和mTOR抑制剂迄今为止疗效有限或没有疗效。显然还需要进一步的研究,以及针对患者的个体化治疗方法。此外,我们还报告了一例未发表的沉默性垂体促肾上腺皮质激素癌病例,该病例在接受双重免疫疗法后病情有所进展,但在接受洛莫司汀和贝伐单抗联合疗法后病情趋于稳定。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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CiteScore
4.60
自引率
0.00%
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146
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