Effectiveness and durability of benefit of mTOR inhibitors in a real-world cohort of patients with metastatic prostate cancer and PI3K pathway alterations.
Effectiveness and durability of benefit of mTOR inhibitors in a real-world cohort of patients with metastatic prostate cancer and PI3K pathway alterations.
复制标题
mTOR 抑制剂在现实世界的患有转移性前列腺癌和 PI3K 通路改变的患者队列中的有效性和持久性。
DOI：
10.1038/s41391-022-00612-8
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发表时间：
2023
影响因子：
4.8
通讯作者：
Lam,ElaineT
中科院分区：
文献类型：
--
作者：
Eule,CorbinJ;Flaig,ThomasW;Wong,Katy;Graf,Ryon;Lam,ElaineT
背景PTEN/PI 3 K/AKT/mTOR通路的改变在前列腺癌中普遍存在。在这项回顾性研究中，我们评估了转移性前列腺癌（mPCA）和组织评估的磷脂酰-3-肌醇激酶（PI 3 K）pathway alterations.MethodsThis研究使用了一个全国性的（美国为基础的）去识别PCA临床基因组数据库，起源于大约280个美国癌症诊所（约800个网站的护理）患者的mTOR抑制剂（mTORi）的临床有效性。我们评估了2014年10月至2020年2月PCA患者的治疗数据。在2301例PCA患者（7208条可评价治疗线）中，我们选择了17例mPCA患者（2例去势敏感，15例去势抵抗），接受mTORi治疗的患者通过综合基因组分析评估PI 3 K通路改变。（IQR 68.0，76.0），并在使用mTORi之前接受了中位3线治疗的重度预治疗（范围0-6）。PI 3 K通路改变包括PTENdel（10例患者，58.8%）、AKT 1 mut（4例患者，23.5%）、PTENmut（2例患者，11.8%）和双重PTENmut和PIK 3CAmut（1例患者，5.9%）。大多数（15例患者，88.2%）接受依维莫司单药治疗。在10例治疗期间PSA可用的患者中，2例患者在第12周时PSA降低≥10%，共有5例患者随后PSA降低。对于那些对mTORi，下一次治疗的中位时间为3.62个月（范围0，8.52）conclusionsIn这个小队列的mPCA患者与组织评估PI 3 K通路改变，mTORi治疗是无效的PSA反应少，治疗时间短。
BackgroundAlterations in the PTEN/PI3K/AKT/mTOR pathway are prevalent in prostate cancer. In this retrospective study, we evaluated the clinical effectiveness of mTOR inhibitors (mTORi) in patients with metastatic prostate cancer (mPCA) and tissue assessed phosphatidyl-3-inositol kinase (PI3K) pathway alterations.MethodsThis study used a nationwide (US-based) de-identified PCA clinico-genomic database, originating from approximately 280 US cancer clinics (~800 sites of care). We evaluated treatment data for patients with PCA from October 2014 to February 2020. In a cohort of 2301 PCA patients with 7208 evaluable treatment lines, we selected 17 mPCA patients (2 hormone-sensitive, 15 castrate-resistant) with tissue assessed PI3K pathway alterations by comprehensive genomic profiling who received mTORi treatment.ResultsPatients had a median age of 72 years (IQR 68.0, 76.0) and were heavily pretreated with a median 3 lines of therapy prior to mTORi use (range 0–6). The PI3K pathway alterations included PTENdel (10 patients, 58.8%), AKT1mut (4 patients, 23.5%), PTENmut (2 patients, 11.8%), and dual PTENmut and PIK3CAmut (1 patient, 5.9%). Most (15 patients, 88.2%) were treated with everolimus monotherapy. Among 10 patients with on treatment PSA available, 2 patients had a PSA decrease ≥10% at week 12 and 5 patients overall had a subsequent PSA decrease. For those on mTORi, the median time to next treatment was 3.62 months (range 0, 8.52).ConclusionsIn this small cohort of mPCA patients with tissue assessed PI3K pathway alterations, mTORi therapy was not effective with few PSA responses and short duration of therapy.