Dana-Farber Cancer Institute, Boston, Massachusetts, USA
Hematology/Oncology Section, Boston University Cancer Center, Boston, Massachusetts, USA.
Oncologist. 2019 Aug;24(8):1056-1065. doi: 10.1634/theoncologist.2018-0519. Epub 2019 Jan 3.
We assessed treatment patterns and outcomes of patients with advanced gastrointestinal (GI) neuroendocrine tumors (NET) at four large tertiary referral centers in the U.S.
We performed a retrospective chart review of patients aged ≥18 years at advanced GI NET diagnosis, treated between July 2011 and December 2014. Index date was the histologically confirmed diagnosis date of locally advanced/metastatic GI NET. Data included baseline characteristics, treatment patterns, progression, death, and GI NET-related health care resource utilization from index date through last contact or death. Time-to-event analyses, including treatment discontinuation, progression, and overall survival (OS), were performed using Kaplan-Meier analysis.
We identified 273 patients; 156 (57%) had primary ileum NET, and 174 (64%) had functional NET. First-line treatments included somatostatin analog (SSA) alone (89%) or in combination (2%), liver-directed therapy (LDT; 8%), and cytotoxic chemotherapy or interferon (2%). One hundred fifty-five patients continued with second-line therapy, including SSA alone (17%) or in combination (75%, with 3% combined with peptide receptor radionuclide therapy), LDT (4%), and other treatments (3%). Median time (months) to first-line discontinuation was 154.0 for SSAs and 3.8 for cytotoxic chemotherapy. Overall median time to investigator-assessed progression following treatment initiation was 30.3 months. Median OS (months) following first-line initiation was 151.8 for all patients and 178.9 for first-line SSA.
Our study illustrates the common use of SSAs in both first-line and subsequent treatment of patients with GI NETs, as well as the relatively long survival durations and multiple additional treatments received by patients with this condition. Treatment pattern assessment at later times, following approval of newer treatments, is warranted.
This study, assessing treatment patterns over a period of up to 30 years, showed that SSAs, LDT, cytotoxic chemotherapy, and interferon are common treatments for advanced GI NETs. SSAs alone or in combination with other treatments were the most frequent therapy in first and subsequent lines. Patients in this study remained on SSAs long-term, with median treatment duration of 12.8 years in first line. Treatment patterns should be assessed beyond this study's time period, given recent U.S. Food and Drug Administration approvals for additional treatments for GI NET, which will likely be incorporated in the continuum of care of patients.
我们评估了美国四家大型三级转诊中心的晚期胃肠道（GI）神经内分泌肿瘤（NET）患者的治疗模式和结局。
我们对 2011 年 7 月至 2014 年 12 月期间诊断为晚期 GI NET 且年龄≥18 岁的患者进行了回顾性病历审查。索引日期为局部晚期/转移性 GI NET 组织学确诊日期。数据包括基线特征、治疗模式、进展、死亡以及从索引日期到最后一次联系或死亡的与 GI NET 相关的医疗资源利用情况。使用 Kaplan-Meier 分析进行了包括治疗中止、进展和总生存期（OS）在内的时间事件分析。
我们共确定了 273 名患者；156 名（57%）患者的原发部位为回肠 NET，174 名（64%）患者的 NET 具有功能性。一线治疗包括单独使用生长抑素类似物（SSA）（89%）或联合使用（2%）、肝定向治疗（LDT；8%）以及细胞毒性化疗或干扰素（2%）。155 名患者继续接受二线治疗，包括单独使用 SSA（17%）或联合使用（75%，其中 3%联合使用肽受体放射性核素治疗）、LDT（4%）和其他治疗（3%）。SSA 组的首次治疗停药中位时间为 154.0 个月，细胞毒性化疗组为 3.8 个月。起始治疗后研究者评估的总体中位进展时间为 30.3 个月。所有患者的首次治疗后中位总生存期（OS）为 151.8 个月，首次治疗 SSA 组为 178.9 个月。
我们的研究说明了 SSA 在 GI NET 患者的一线和后续治疗中的广泛应用，以及此类患者的相对较长的生存时间和接受的多种额外治疗。需要在较晚时间（在批准新治疗后）评估治疗模式。
这项研究评估了长达 30 年的治疗模式，表明 SSA、LDT、细胞毒性化疗和干扰素是晚期 GI NET 的常见治疗方法。SSA 单独或与其他治疗联合是一线和二线最常见的治疗方法。该研究中的患者长期使用 SSA，一线治疗的中位治疗时间为 12.8 年。鉴于美国食品和药物管理局最近批准了 GI NET 的其他治疗方法，这些方法可能会纳入患者的连续护理中，因此应在本研究时间范围之外评估治疗模式。
