IGF-1 axis changes with ADT and docetaxel in metastatic prostate cancer.

IF 4.1 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Endocrine-related cancer Pub Date : 2023-10-04 Print Date: 2023-11-01 DOI:10.1530/ERC-23-0241
Praful Ravi, Victoria Wang, Raina N Fichorova, Bradley McGregor, Xiao X Wei, Shehzad Basaria, Christopher J Sweeney
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Abstract

Androgen deprivation therapy (ADT) forms the cornerstone of treatment in locally advanced and metastatic prostate cancer (PCa). Since the growth hormone-insulin-like growth factor (GH-IGF-1) axis has been implicated in prostate tumorigenesis, we aimed to evaluate the association between IGF-1 and its binding proteins on outcomes in men with metastatic PCa treated with ADT, with or without docetaxel (D). We analyzed serum samples for IGF-1 and its family proteins from baseline, 6 months post-randomization, and at the time of progression in men enrolled to receive ADT +/- D in the phase 3 CHAARTED trial. The key outcomes were time to the development of castrate-resistant prostate cancer and overall survival (OS). About 560 patients had samples available for analysis. At 6 months, significant increases in IGF-BP1 (mean Δ+27.4%, P = 0.033), IGF-BP3 (mean Δ+10.3%, P < 0.001), and IGF-BP4 (mean Δ+31.1%, P < 0.001) were seen in the ADT + D group, while the ADT group showed an increase in IGF-BP3 (mean Δ+5.5%, P = 0.015). A higher IGF-1:IGF-BP1 ratio at baseline and after 6 months was associated with improved OS in both the ADT (baseline: hazard ratio (HR) = 0.77, P = 0.026; 6 months: HR = 0.83, P = 0.036) and ADT + D groups (baseline: HR = 0.78, P = 0.04; 6 months: HR = 0.81, P = 0.018). Patients with a log10IGF-1:IGF-BP1 ratio >1.3 at baseline had improved OS when meta-analyzed with data from a prior cohort (HR = 0.71). A higher baseline and 6-month IGF-1:IGF-BP1 ratio was associated with better OS. Further exploration of the IGF-1 axis will be important to assess its role as a predictive biomarker and to target this axis in therapeutic trials.

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转移性前列腺癌症中IGF-1轴随ADT和多烯紫杉醇的变化。
雄激素剥夺疗法(ADT)是局部晚期和转移性癌症(PCa)治疗的基石。由于生长激素-胰岛素样生长因子(GH-IGF-1)轴与前列腺肿瘤的发生有关,我们旨在评估IGF-1及其结合蛋白对接受ADT、接受或不接受多西他赛(D)治疗的转移性前列腺癌患者预后的影响。我们分析了基线、随机分组后6个月以及在3期CHAARTED试验中接受ADT+/-D的男性进展时的血清样本中IGF-1及其家族蛋白。关键结果是去势耐受性前列腺癌症的发展时间和总生存率(OS)。大约560名患者的样本可供分析。在6个月时,ADT+D组的IGF-BP1(平均Δ+27.4%,P=0.033)、IGF-BP3(平均Δ+10.3%,P<0.001)和IGF-BP4(平均Δ+31.1%,P=0.001)显著增加,而ADT组显示IGF-BP3增加(平均Δ+5.5%,P=0.015)。基线和6个月后IGF-1:IGF-BP1比率较高与两组ADT的OS改善相关(基线:危险比(HR)=0.77,P=0.026;6个月:HR=0.83,P=0.036)和ADT+D组(基线:HR=0.78,P=0.04;6个月,HR=0.81,P=0.018)。当与先前队列的数据进行荟萃分析时,基线时log10IGF-1:IGF-BP1比率>1.3的患者的OS有所改善(HR=0.71)。基线和6个月时IGF-1/IGF-BP1比率越高,OS越好。对IGF-1轴的进一步探索对于评估其作为预测性生物标志物的作用以及在治疗试验中靶向该轴将是重要的。
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来源期刊
Endocrine-related cancer
Endocrine-related cancer 医学-内分泌学与代谢
CiteScore
7.80
自引率
2.60%
发文量
138
审稿时长
6-12 weeks
期刊介绍: Endocrine-Related Cancer is an official flagship journal of the Society for Endocrinology and is endorsed by the European Society of Endocrinology, the United Kingdom and Ireland Neuroendocrine Society, and the Japanese Hormones and Cancer Society. Endocrine-Related Cancer provides a unique international forum for the publication of high quality original articles describing novel, cutting edge basic laboratory, translational and clinical investigations of human health and disease focusing on endocrine neoplasias and hormone-dependent cancers; and for the publication of authoritative review articles in these topics. Endocrine neoplasias include adrenal cortex, breast, multiple endocrine neoplasia, neuroendocrine tumours, ovary, prostate, paraganglioma, parathyroid, pheochromocytoma pituitary, testes, thyroid and hormone-dependent cancers. Neoplasias affecting metabolism and energy production such as bladder, bone, kidney, lung, and head and neck, are also considered.
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