Division of Medical Oncology, Duke University Medical Center, Durham, North Carolina.
Seagen Inc., Bothell, Washington.
J Natl Compr Canc Netw. 2023 Aug;21(8):805-812.e1. doi: 10.6004/jnccn.2023.7022.
HER2 amplification (HER2+) occurs in approximately 3% of patients with metastatic colorectal cancer (mCRC). Despite the recent addition of HER2-directed therapies to treatment recommendations in the NCCN Guidelines, until more recently there were no FDA-approved treatments. This study examined real-world treatment patterns in patients with HER2+ mCRC in the United States before and after the emerging awareness of HER2-directed therapies in 2018.
This was a retrospective observational study of patients with HER2+ mCRC from the GuardantINFORM database, which contains claims data for patients with Guardant360 genomic testing results. Patients were aged ≥18 years, were diagnosed with mCRC between January 2014 and September 2020, and had confirmed ERBB2 amplification via the blood-based Guardant360 test. Treatment patterns and real-world time to next treatment (rwTTNT) were evaluated.
This study included 142 patients with a median age of 59 years; 31 (21.8%) patients with ERBB2 amplifications also had ERBB2 mutations. Treatment patterns were heterogeneous and evolved over time; before 2018, the most common regimen prescribed after detection of ERBB2 amplification was anti-VEGF therapy with or without chemotherapy (31.6%; n=25), and after 2018, HER2-directed therapies were the most commonly prescribed (36.5%; n=23). Median rwTTNT among the overall cohort was 8.4 months (95% CI, 6.5-10.0); rwTTNT was numerically longer in patients who received HER2-directed therapy compared with those who received non-HER2-directed therapies (11.0 months [95% CI, 6.3-12.3] vs 7.2 months [95% CI, 5.8-9.6]).
This real-world study of the largest clinically annotated dataset of patients with HER2+ mCRC showed that many patients do not receive HER2-directed therapy despite its inclusion in NCCN Guidelines, with heterogeneous treatment patterns suggesting that standard of care remains undefined and targeted therapy remains underutilized. Greater awareness of the unmet need in this patient population, together with new effective therapies, will facilitate strategies for improved, targeted treatment approaches.
HER2 扩增（HER2+）发生在约 3%的转移性结直肠癌（mCRC）患者中。尽管最近在 NCCN 指南中增加了针对 HER2 的治疗建议，但直到最近，还没有 FDA 批准的治疗方法。本研究在美国考察了 2018 年出现针对 HER2 的治疗方法后，HER2+ mCRC 患者的真实世界治疗模式。
这是一项回顾性观察性研究，纳入了 GuardantINFORM 数据库中的 HER2+ mCRC 患者，该数据库包含了 Guardant360 基因组检测结果的患者理赔数据。患者年龄≥18 岁，于 2014 年 1 月至 2020 年 9 月诊断为 mCRC，并且通过血液检测 Guardant360 确诊为 ERBB2 扩增。评估了治疗模式和真实世界的下一次治疗时间（rwTTNT）。
本研究共纳入 142 例患者，中位年龄 59 岁；31 例（21.8%）患者同时存在 ERBB2 扩增和 ERBB2 突变。治疗模式存在异质性，且随时间演变；在 2018 年之前，检测到 ERBB2 扩增后最常见的治疗方案是抗血管内皮生长因子治疗联合或不联合化疗（31.6%；n=25），而在 2018 年之后，针对 HER2 的治疗最常被开具（36.5%；n=23）。整体队列的中位 rwTTNT 为 8.4 个月（95%CI，6.5-10.0）；接受 HER2 靶向治疗的患者 rwTTNT 数值长于接受非 HER2 靶向治疗的患者（11.0 个月[95%CI，6.3-12.3]vs 7.2 个月[95%CI，5.8-9.6]）。
本研究是一项对最大的临床注释数据集的真实世界研究，该研究显示，尽管 HER2 靶向治疗被纳入了 NCCN 指南，但许多患者并未接受该治疗，治疗模式存在异质性，这表明标准治疗方法仍未确定，靶向治疗的利用率仍较低。提高对这一患者群体的未满足需求的认识，以及新的有效治疗方法，将有助于制定更好的、有针对性的治疗方法策略。
