Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy; PhD course in Clinical and Experimental Oncology and Immunology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy; School of Specialization in Medical Oncology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
Eur J Cancer. 2023 Sep;191:112959. doi: 10.1016/j.ejca.2023.112959. Epub 2023 Jun 22.
Next-generation sequencing (NGS) panels enable the identification of alterations in cancer-related genes. This may guide a molecularly targeted strategy for the treatment of glioblastoma (GBM).
We retrospectively analysed data obtained using FoundationOne®CDx in a large cohort of IDH1/2 wild-type GBM. We aimed to 1) identify potentially actionable molecular alterations at diagnosis and/or recurrence based on ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) defined categories of targetability, 2) understand the clinical implications of NGS in terms of access to and activity of targeted therapies.
In 442 samples, an NGS profile was available in 98.2%. The median time from diagnosis to NGS profiling was 7.4 months (interquartile range (IQR): 3.4-13.2). Although about half of the patients had at least one actionable molecular alteration, only 3.4% of them were classified as ESCAT IB-IC and 6.7% as ESCAT IIB. Only 36 patients (10.5%) received personalised treatment in clinical trials or as off-label/compassionate use from second-line (median line 3). Most patients did not receive targeted therapy due to clinical deterioration/death (49.6%). Patients treated with dabrafenib/trametinib (9 patients) had the highest disease control rate of 77% and an objective response rate of 22%, with a median progression-free survival (PFS) of 5.2 months. No complete/partial responses were seen with the other regimens. 4/9 (44.4%) patients on anti-BRAF/anti-MEK, 2/4 patients (50%) on erdafitinib and 1/1 patient on capmatinib had a PFS ratio > 1.3. One recurrent GBM patient with ROS1-GOCP fusion maintained a complete response for 11.3 months on entrectinib.
Our study demonstrated the feasibility of NGS in GBM samples. As the number of clinically relevant targets was limited and only a small group of GBM patients were treated with targeted therapy, NGS testing should be performed in the context of clinical trials. Our results support the activity of anti-BRAF/anti-MEK, while for the other agents prospective study results are needed to draw solid conclusions.
下一代测序（NGS）面板能够鉴定与癌症相关的基因改变。这可能为胶质母细胞瘤（GBM）的分子靶向治疗提供指导。
我们回顾性分析了使用 FoundationOne®CDx 在 IDH1/2 野生型 GBM 大样本中的数据。我们旨在：1）根据 ESMO 分子靶向治疗可操作性量表（ESCAT）定义的靶标可操作性类别，在诊断时和/或复发时确定潜在的可操作分子改变；2）了解 NGS 在获得和应用靶向治疗方面的临床意义。
在 442 例样本中，有 98.2%可获得 NGS 图谱。从诊断到 NGS 分析的中位时间为 7.4 个月（四分位间距（IQR）：3.4-13.2）。尽管约一半的患者至少有一种可操作的分子改变，但只有 3.4%的患者被归类为 ESCAT IB-IC，6.7%的患者被归类为 ESCAT IIB。仅有 36 例（10.5%）患者接受了临床试验中的个性化治疗或二线治疗的个体化治疗（中位线 3）。由于临床恶化/死亡，大多数患者未接受靶向治疗（49.6%）。接受 dabrafenib/trametinib（9 例）治疗的患者疾病控制率最高（77%），客观缓解率为 22%，中位无进展生存期（PFS）为 5.2 个月。其他方案未见完全/部分缓解。抗 BRAF/抗 MEK 治疗的 4/9（44.4%）例患者、抗 erdafitinib 治疗的 2/4 例患者（50%）和抗 capmatinib 治疗的 1/1 例患者的 PFS 比值>1.3。一名 ROS1-GOCP 融合的复发性 GBM 患者接受 entrectinib 治疗 11.3 个月后保持完全缓解。
我们的研究证明了 NGS 在 GBM 样本中的可行性。由于临床相关靶点数量有限，只有一小部分 GBM 患者接受了靶向治疗，因此 NGS 检测应在临床试验的背景下进行。我们的结果支持抗 BRAF/抗 MEK 的活性，而对于其他药物，需要前瞻性研究结果来得出确凿的结论。
