Ny Lars, Fagman Henrik, Botling Johan, Mantovaara Loviisa, Asplund Peter, Karlsson Hannah, Aust Jennie, Abel Edvard, Hellström Mats, Crona Joakim, Nygren Peter
Institute of Clinical Sciences, Department of Oncology, University of Gothenburg, Gothenburg, Sweden, Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden.
Department of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Center for Cancer Research, University of Gothenburg, Gothenburg, Sweden.
Acta Oncol. 2025 Jun 4;64:742-750. doi: 10.2340/1651-226X.2025.43366.
Precision cancer medicine (PCM) is key to advancing cancer treatment beyond the standard of care. We performed an explorative clinical trial, MEGALiT, to investigate the feasibility, safety, and clinical benefit of genomics-based PCM in advanced cancer.
MEGALiT recruited adult patients with advanced solid tumors refractory to standard treatment. Tumor DNA from newly acquired biopsies or ctDNA were analyzed for alterations targetable with the PD-L1 inhibitor atezolizumab, the MEK inhibitor cobimetinib, the mTOR inhibitor everolimus, or the PARP-inhibitor niraparib. Any other 'in study' treatment was left to the discretion of the physician.
Outcome data are reported for 153 patients. The median age was 65 years and the most common diagnoses were colorectal, prostate, and ovarian cancer. The median time from study inclusion to the Molecular Tumor Board was 35 days for tumor sampling by biopsy and 21 days by ctDNA. Of the 44 patients allocated to a study drug, 38 started treatment. The median follow-up was 1.9 years. Of the patients on a study drug and evaluable for tumor response, 6% (2/32) had partial remission, and 25% (8/32) had disease control at 16 weeks. Median overall survival for patients starting a study drug was longer, 7.4 months, compared to 2.7 months for the 61 untreated patients (HR 0.43; log-rank p < 0.0001), but shorter than for the 50 patients receiving treatment of physician's choice, 11.8 months (HR 0.55; log-rank p = 0.012). No significant procedure- or drug-related severe adverse events were observed.
Genomics-guided treatment selection in advanced cancer is feasible and safe. However, evidence of patient benefit warrants further investigation.
精准癌症医学（PCM）是推动癌症治疗超越现有治疗标准的关键。我们开展了一项探索性临床试验MEGALiT，以研究基于基因组学的PCM在晚期癌症中的可行性、安全性和临床获益情况。
MEGALiT招募了对标准治疗难治的晚期实体瘤成年患者。对新获取的活检组织或循环肿瘤DNA（ctDNA）中的肿瘤DNA进行分析，以检测可被程序性死亡配体1（PD-L1）抑制剂阿特珠单抗、丝裂原活化蛋白激酶激酶（MEK）抑制剂考比替尼、哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂依维莫司或聚腺苷酸聚合酶（PARP）抑制剂尼拉帕利靶向的改变。任何其他“研究中”的治疗均由医生自行决定。
报告了153例患者的结局数据。中位年龄为65岁，最常见的诊断为结直肠癌、前列腺癌和卵巢癌。从纳入研究到分子肿瘤委员会的中位时间，活检取样为35天，ctDNA取样为21天。在分配到研究药物的44例患者中，38例开始治疗。中位随访时间为1.9年。在接受研究药物治疗且可评估肿瘤反应的患者中，6%（2/32）有部分缓解，25%（8/32）在16周时疾病得到控制。开始使用研究药物的患者的中位总生存期更长，为7.4个月，而61例未治疗患者的中位总生存期为2.7个月（风险比[HR]0.43；对数秩检验p<0.0001），但短于50例接受医生选择治疗的患者，为11.8个月（HR 0.55；对数秩检验p=0.012）。未观察到与操作或药物相关的严重不良事件。
晚期癌症中基于基因组学的治疗选择是可行且安全的。然而，患者获益的证据值得进一步研究。
