Department of Medicine, School of Medicine, Duke University, Durham, NC.
Department of Radiology, Duke University, Durham, NC.
Urol Oncol. 2019 Nov;37(11):813.e1-813.e9. doi: 10.1016/j.urolonc.2019.06.015. Epub 2019 Jul 19.
Targeted inhibitors and immunotherapy have entered the treatment landscape of metastatic prostate cancer. Genomic testing may uncover which patients benefit most from these therapies. We report the clinical utility and benefits of FoundationOne testing in men with advanced prostate cancer.
We retrospectively identified all men with prostate cancer who received tissue FoundationOne testing at our institution between January 2010 and April 2017. Genomic alterations, treatment selection based on FoundationOne results, and clinical outcomes including response and duration of therapy following matched targeted therapy were analyzed.
A total of 77 men with metastatic prostate cancer were referred for FoundationOne testing; 59 (77%) had sufficient tumor tissue for testing. Of these, 22% (17/77) of men had a targetable mutation and 9% (7/77) of men received matched off-label targeted therapy. Overall, 5% (4/77) of patients derived clinical benefit. One patient with a BRCA2 loss had a complete response on olaparib (>27 months) and 3 patients (ATM substitution, PALB2 frameshift, CDK12 frameshift) had stable disease with olaparib (10.3, 18.7, and 7.8 months, respectively). Three patients (BRCA2 frameshift, PDL1 + PDL2 amplification, PMS2 missense) had progressive disease despite targeted therapy.
Tissue genomic testing can uncover patients who may benefit from targeted therapies such as poly(adenosine diphosphate-ribose) polymerase inhibitors or immunotherapy. In our limited single institution study, genomic testing led to clinical benefit in 5% of patients. Combined germline and circulating tumor DNA testing may be helpful to identify additional patients suitable for matched genomic therapies.
靶向抑制剂和免疫疗法已进入转移性前列腺癌的治疗领域。基因组检测可能会发现哪些患者最能从这些疗法中获益。我们报告了 FoundationOne 检测在晚期前列腺癌男性中的临床应用和获益。
我们回顾性地确定了 2010 年 1 月至 2017 年 4 月期间在我们机构接受组织 FoundationOne 检测的所有前列腺癌男性患者。分析了基因组改变、根据 FoundationOne 结果选择的治疗方法，以及在接受匹配的靶向治疗后，包括反应和治疗持续时间在内的临床结局。
共有 77 名转移性前列腺癌男性患者被转介进行 FoundationOne 检测；59 名（77%）有足够的肿瘤组织进行检测。其中，22%（17/77）的男性有可靶向的突变，9%（7/77）的男性接受了匹配的、非适应证的靶向治疗。总体而言，5%（4/77）的患者获得了临床获益。一名携带 BRCA2 缺失的患者在奥拉帕利治疗中获得完全缓解（>27 个月），3 名患者（ATM 取代、PALB2 移码、CDK12 移码）在奥拉帕利治疗中疾病稳定（分别为 10.3、18.7 和 7.8 个月）。尽管接受了靶向治疗，但 3 名患者（BRCA2 移码、PDL1+PDL2 扩增、PMS2 错义）仍出现疾病进展。
组织基因组检测可以发现可能从聚（腺苷二磷酸核糖）聚合酶抑制剂或免疫疗法等靶向治疗中获益的患者。在我们的单中心研究中，基因组检测使 5%的患者获得了临床获益。联合种系和循环肿瘤 DNA 检测可能有助于识别更多适合匹配基因组治疗的患者。
