Department of Medical Oncology, Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, India.
Department of Medical Oncology, Homi Bhabha Cancer Hospital, Varanasi, India.
J Clin Oncol. 2024 Mar 1;42(7):800-807. doi: 10.1200/JCO.23.01193. Epub 2023 Nov 9.
Human epidermal growth factor receptor 2 (HER2) overexpression is seen in 4%-16% of biliary tract cancers (BTCs). We aimed to evaluate the clinical activity of gemcitabine-cisplatin (GC) plus anti-HER2 antibody trastuzumab as initial treatment in HER2-positive BTCs.
This study was an investigator-initiated, open-label, single-arm, multi-institutional, phase II trial in adult patients with HER2-positive (defined as immunohistochemistry [IHC] 3+ or IHC 2+ and fluorescent in situ hybridization-positive), treatment-naïve BTCs. The primary end point of the study was 6-month progression-free survival (PFS). Next-generation sequencing was performed on tissue samples to evaluate mutational status.
From March 2020 to August 2022, of the 876 screened patients, 118 (13.4%) were found to have HER2-positive status, of whom 90 were enrolled in the study. Most patients had GBC (n = 96; 96%) with two or more sites of metastatic disease (n = 70; 78%). With a median follow-up of 17.3 (95% CI, 15.22 to 19.32) months, 72 patients had disease progression with a median PFS of 7 (95% CI, 6.2 to 7.8) months. The diagnosis to event 6-month PFS rate was 75.6% (95% CI, 66.6 to 84.6). A complete or partial response was seen in 50 (55.5%) patients and 22 (24.4%) patients had stable disease as the best response to treatment, for an overall disease control rate of 80%. The presence of isolated TP53 mutations was associated with inferior PFS compared with other mutations (TERT promoter, HER2, PIK3CA, etc) or no detected mutations (6.51 12.02 10.58 months; < .001).
The combination of GC and trastuzumab achieved its primary end point of improving PFS compared with historical data in the treatment-naïve HER2-positive BTC. Evaluating additional mutations such as TP53 and PIK3CA along with HER2 testing may help to preferentially select patients for anti-HER2 therapy in the future (Clinical Trial Registry India number: CTRI/2019/11/021955).
人表皮生长因子受体 2（HER2）过表达可见于 4%-16%的胆道癌（BTC）患者中。我们旨在评估吉西他滨联合顺铂（GC）加抗 HER2 抗体曲妥珠单抗作为 HER2 阳性 BTC 初始治疗的临床疗效。
这是一项由研究者发起的、开放标签、单臂、多中心、Ⅱ期临床试验，纳入未经治疗的 HER2 阳性（定义为免疫组化[IHC]3+或 IHC 2+且荧光原位杂交阳性）BTC 成年患者。该研究的主要终点为 6 个月无进展生存期（PFS）。对组织样本进行下一代测序以评估突变状态。
2020 年 3 月至 2022 年 8 月，在筛选的 876 例患者中，有 118 例（13.4%）被发现 HER2 阳性，其中 90 例入组该研究。大多数患者为胆囊癌（GBC，n=96；96%），且有两个或更多转移部位（n=70；78%）。中位随访 17.3 个月（95%CI：15.22-19.32）时，72 例患者出现疾病进展，中位 PFS 为 7 个月（95%CI：6.2-7.8）。诊断至事件 6 个月 PFS 率为 75.6%（95%CI：66.6-84.6）。50 例患者（55.5%）获得完全或部分缓解，22 例患者（24.4%）疾病最佳缓解为稳定，疾病总体控制率为 80%。与其他突变（TERT 启动子、HER2、PIK3CA 等）或未检测到突变相比，孤立性 TP53 突变与更差的 PFS 相关（6.51 12.02 10.58 个月；<.001）。
与未经治疗的 HER2 阳性 BTC 的历史数据相比，GC 联合曲妥珠单抗治疗可改善 PFS，达到主要研究终点。评估额外的突变，如 TP53 和 PIK3CA，以及 HER2 检测，可能有助于未来优先选择接受抗 HER2 治疗的患者（印度临床试验注册中心编号：CTRI/2019/11/021955）。
