Genomic profiling is critical for the identification of treatment options for patients with metastatic cancer, but it remains unclear how frequently this procedure should be repeated during the course of the disease. To address this, we analyzed whole-genome sequencing (WGS) data of 250 biopsy pairs, longitudinally collected over the treatment course of 231 adult patients with a representative variety of metastatic solid malignancies. Within the biopsy interval (median, 6.4 months), patients received one or multiple lines of (mostly) standard-of-care (SOC) treatments, with all major treatment modalities being broadly represented. SOC biomarkers and biomarkers for clinical trial enrollment could be identified in 23% and 72% of biopsies, respectively. For SOC genomic biomarkers, we observed full concordance between the first and the second biopsy in 99% of pairs. Of the 219 biomarkers for clinical trial enrollment that were identified in the first biopsies, we recovered 94% in the follow-up biopsies. Furthermore, a second WGS analysis did not identify additional biomarkers for clinical trial enrollment in 91% of patients. More-frequent genomic evolution was observed when considering specific genes targeted by small-molecule inhibitors or hormonal therapies (21% and 22% of cases, respectively). Together, our data demonstrate that there is limited evolution of the actionable genome of treated metastases. A single WGS analysis of a metastatic biopsy is generally sufficient to identify SOC genomic biomarkers and to identify investigational treatment opportunities.

基因组分析对于确定转移性癌症患者的治疗方案至关重要，但目前尚不清楚在疾病过程中应以何种频率重复该过程。为了解决这个问题，我们分析了 250 个活检对的全基因组测序 (WGS) 数据，这些数据是在 231 名患有代表性转移性实体恶性肿瘤的成年患者的治疗过程中纵向收集的。在活检间隔（中位时间为 6.4 个月）内，患者接受了一种或多种（大部分）标准护理 (SOC) 治疗，所有主要治疗方式均得到广泛体现。 SOC 生物标志物和临床试验入组生物标志物可分别在 23% 和 72% 的活检中被识别。对于 SOC 基因组生物标志物，我们观察到 99% 的配对中第一次和第二次活检之间完全一致。在首次活检中鉴定出的用于临床试验入组的 219 种生物标志物中，我们在后续活检中恢复了 94%。此外，第二次全基因组测序分析并未发现 91% 患者的临床试验招募的额外生物标志物。当考虑小分子抑制剂或激素疗法针对的特定基因时，观察到更频繁的基因组进化（分别为 21% 和 22% 的病例）。总之，我们的数据表明，治疗转移的可操作基因组的进化有限。转移性活检的单次全基因组测序分析通常足以识别 SOC 基因组生物标志物并确定研究性治疗机会。