Medical Oncology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
Int J Mol Sci. 2022 Aug 1;23(15):8535. doi: 10.3390/ijms23158535.
Precision medicine has opened up a new era in the development of anti-cancer agents that is focused on identifying biomarkers predictive of treatment response regardless of tumor histology. Since 2017, the Food and Drug Administration has approved six drugs with histology-agnostic indications: pembrolizumab (both for tumors with the mismatch-repair deficiency (dMMR)/high microsatellite instability (MSI-H) phenotype and for those with the high tumor mutational burden (TMB-H) phenotype), dostarlimab (for dMMR tumors), larotrectinib and entrectinib (for tumors harboring neurotrophic tyrosine receptor kinase (NTRK) fusions), and the combination of dabrafenib plus trametinib (for BRAF V600E-mutated tumors). The genomic alterations targeted by these antineoplastic agents are rare in metastatic castration-resistant prostate cancer (mCRPC). Furthermore, only a small number of mCRPC patients were enrolled in the clinical trials that led to the approval of the above-mentioned drugs. Therefore, we critically reviewed the literature on the efficacy of histology-agnostic drugs in mCRPC patients. Although the available evidence derives from retrospective studies and case reports, our results confirmed the efficacy of pembrolizumab in dMMR/MSI-H mCRPC. In contrast, few data are available for dostarlimab, larotrectinib, entrectinib, and dabrafenib-trametinib in this subset of patients. Large, multi-institutional registries aimed at collecting real-world data are needed to better comprehend the role of tissue-agnostic drugs in mCRPC patients.
精准医学开启了抗癌药物发展的新时代，其重点是识别预测治疗反应的生物标志物，而不论肿瘤组织学如何。自 2017 年以来，美国食品和药物管理局已批准了 6 种具有组织学不可知特征的药物：pembrolizumab（均用于错配修复缺陷（dMMR）/高微卫星不稳定性（MSI-H）表型的肿瘤和高肿瘤突变负担（TMB-H）表型的肿瘤）、dostarlimab（用于 dMMR 肿瘤）、larotrectinib 和 entrectinib（用于携带神经营养酪氨酸受体激酶（NTRK）融合的肿瘤），以及 dabrafenib 加 trametinib（用于 BRAF V600E 突变的肿瘤）。这些抗肿瘤药物靶向的基因组改变在转移性去势抵抗性前列腺癌（mCRPC）中很少见。此外，只有少数 mCRPC 患者参加了导致上述药物批准的临床试验。因此，我们批判性地审查了组织学不可知药物在 mCRPC 患者中的疗效的文献。尽管现有证据来自回顾性研究和病例报告，但我们的结果证实了 pembrolizumab 在 dMMR/MSI-H mCRPC 中的疗效。相比之下，在这组患者中， dostarlimab、larotrectinib、entrectinib 和 dabrafenib-trametinib 的数据很少。需要大型、多机构登记处来收集真实世界的数据，以更好地理解组织学不可知药物在 mCRPC 患者中的作用。
