编者按：精彩继续！2023年我国在胃癌领域取得了多方面突破，覆盖诊断手段、治疗策略，以及分子机制探索等，本文继续回顾与总结了2023年我国胃癌领域最新研究进展，快跟小编一起来看看吧！
01
T-DXd用于中国HER2阳性晚期胃癌患者新添力证
研究名称
DESTINY-Gastric06（DG06）研究：中国HER2阳性局部晚期/转移性胃癌（GC）或胃食管交界处腺癌（GEJA）的经治患者使用T-DXd治疗的II期、单臂研究的主要疗效和安全性背景
对于中国人表皮生长因子受体2（HER2）阳性晚期/复发性GC/GEJA患者，当前的治疗选择有限。目前，靶向HER2的抗体药物偶联物 (ADC) 代表性药物德曲妥珠单抗（T-DXd）已在美国、欧盟、日本、韩国和新加坡获批，用于治疗含曲妥珠单抗方案经治的成人局部晚期/转移性GC/GEJA。DESTINY-Gastric01（DG01）临床试验结果显示，对于HER2阳性晚期GC/GEJA患者，在日本和韩国人群中，T-DXd较标准治疗方案在缓解率和总生存期（OS）都显示出更大的优势。方法
在这项开放标签、单臂、Ⅱ期临床研究中，对既往接受过≥2线治疗（包括氟尿嘧啶、铂类）的HER2阳性（IHC3+；IHC2+/ISH+）晚期GC/GEJA患者予以T-DXd 6.4 mg/kg静脉输注，每3周一次。
主要研究终点为根据RECIST v1.1标准的独立中心审查（ICR）确认的客观缓解率（ORR）。次要研究终点包括研究者评估（INV）确认的ORR、缓解持续时间（DOR）、无进展生存期（PFS）和OS。结果
截至2023年6月16日，研究共纳入95例意向治疗患者入组，其中73例确诊为HER2阳性（IHC3+或IHC2+/ISH+），纳入全分析集（FAS）。在FAS中，65.8%的患者年龄在65岁以下，72.6%的患者为IHC3+，30.1%的患者的原发肿瘤为食管癌。
中位随访8个月，HER2阳性患者中INV评估的mPFS为5.7个月，mOS为10.2个月，ORR为28.8%，DCR为79.4%，mDOR为7.9个月。安全性方面，最常见的不良事件为贫血、白细胞减少和中性粒细胞减少，均为临床管理较为成熟且可控的不良事件。确定与T-DXd相关的ILD/肺炎发生率3.2%，均为1-2级，由此T-DXd的安全性得到确证。结论
初步分析显示，T-DXd对于HER2阳性晚期GC/GEJA具有显著的临床意义的获益，并且安全性可控，尽管该研究纳入的患者基线特征相对更差，并且在全球COVID-19大流行时期开展，但仍取得了与DG01研究一致的临床获益。
02
中国UAM GC/GEJA患者1L和2L治疗急需新的治疗选择
研究名称
中国不能切除的晚期或转移性（UAM）GC/GEJA患者的治疗模式和临床结局:一项多中心真实世界研究背景
本研究旨在调查在真实世界中，中国UAM GC/GEJA患者的特征、治疗模式和临床结局。方法
本研究是一项多中心、回顾性、观察性研究，使用了四家三级医院的电子病历。纳入了在2017年1月1日至2020年12月31日期间被诊断患有UAM GC/GEJA，并且从诊断到2021年8月31日至少有1次因UAM GC/GEJA住院治疗的成年患者。采用描述性统计对数据进行总结，Kaplan-Meier用于描述各治疗方案的治疗持续时间（DoT）和PFS。结果
在2745例符合条件的患者（中位年龄62岁，69.2%为男性）中，97.3%被诊断为GA，94.0%为IV期，43.4%在诊断时有腹膜转移。在所有符合条件的患者中，1902例（69.3%）接受了一线（1L）治疗，其中729例患者（38.3%）接受了二线（2L）治疗，284例患者（14.9%）接受了三线（3L）治疗。大多数患者1L和2L治疗为单独化疗（1L 84.1%，2L 63.6%，3L 41.4%）。在3L治疗中，以靶向治疗方案（1L 13.7%，2L 30.3%，3L 49.2%）和免疫治疗（1L 3.1%，2L 8.7%，3L 18.5%）更为常用。1L、2L和3L最常用的治疗方案分别是氟嘧啶（FP）联合铂（44.5%）、FP联合紫杉烷（16.5%）和单药抗血管生成小分子酪氨酸激酶抑制剂（18.2%）。
中位DoT：1L为4.4个月，2L为3.1个月，3L为2.4个月；中位PFS：1L为6.5个月，2L为4.2个月，3L为3.2个月，随着治疗方案的推进DOT和PFS均逐渐降低。结论
UAM GC/GEJA患者1L和2L治疗以单独化疗为主，但DoT和PFS普遍较短，这表明此类患者1L和2L治疗可能需要更加有效的新治疗方案。
03
呋喹替尼联合化疗或可成为晚期胃癌ICI耐药后的全新方案
研究名称
呋喹替尼联合白蛋白结合型紫杉醇二线治疗经含免疫检查点抑制剂治疗失败的局部晚期/转移性GC/GEJC的疗效和安全性：一项单中心前瞻性临床研究背景
免疫检查点抑制剂（ICIs）不仅为GC/GEJA患者早期治疗提供了新的选择，而且据观察，与化疗相比，早期使用ICI治疗可以增强VEGFR抑制剂联合晚期化疗的疗效。本项单中心前瞻性临床研究旨在探讨呋喹替尼联合白蛋白结合型紫杉醇二线治疗经含免疫检查点抑制剂治疗失败的局部晚期/转移性GC/GEJC患者的疗效和安全性。方法
纳入一线治疗使用过ICI的晚期G/GEJ患者42例，以3周为一周期，紫杉醇（100g/m2，D1,D8），呋喹替尼（4mg，D1-D14）。主要终点为PFS。结果
截至2023年8月10日，共入组25例患者，其中23例可评估。在可评估组中14例患者为男性。所有这些患者的TNM分期均为IV期，中位年龄为58岁，其中6例患者年龄超过65岁。12例患者的PD-L1 CPS大于1，9例患者大于5，4例患者大于10，另有4例患者的PD-L1 CPS未知。患者接受早期中位ICI治疗周期数为5，出现腹膜后淋巴结转移患者17例（73.9%），肝转移患者7例（30.4%）。
中位随访5.6个月，PFS达到4.8个月。尽管未达到总生存期（OS），但1年OS率为56.25%（95%CI：17.27%-95.23%）。ORR为47.8% (n=11)，DCR为100%(n=23)。就安全性而言，最常见（≥20%）的各级AE均为白细胞减少、周围神经病变和中性粒细胞减少症，≥3级的AE为白细胞减少。结论
呋喹替尼联合白蛋白结合型紫杉醇二线治疗经含ICIs治疗失败的局部晚期/转移性GC/GEJC表现出了良好的疗效和安全性，并且ICI可能会增加这种疗法的获益，但这需要在大型队列中进行进一步研究。摘要原文
172P-Trastuzumab deruxtecan (T-DXd) in Chinese patients (pts) with previously treated HER2-positive locally advanced/metastatic gastric cancer (GC) or gastroesophageal junction adenocarcinoma (GEJA): Primary efficacy and safety from the phase II single-arm DESTINY-Gastric06 (DG06) trial
Background
For pts with HER2-positive advanced/recurrent GC/GEJA in China, treatment options are limited. T-DXd is a HER2-directed antibody-drug conjugate; T-DXd 6.4 mg/kg is approved in the US, EU, Japan, South Korea and Singapore for treatment of locally advanced/metastatic GC/GEJA in adults who received a prior trastuzumab-based regimen. In DESTINY-Gastric01 (DG01), T-DXd showed significant improvements in response rates and overall survival (OS) versus standard therapies in pts from Japan/South Korea with HER2-positive advanced GC/GEJA.
Methods
In this open-label, single-arm, phase 2 trial (NCT04989816), Chinese pts with HER2-positive (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization [ISH]+ by central laboratory) advanced GC/GEJA who had received ≥2 prior treatment regimens, including a fluoropyrimidine and a platinum agent, received T-DXd 6.4 mg/kg intravenous infusion once every 3 weeks. Primary endpoint was confirmed objective response rate (ORR) by independent central review (ICR) per RECIST v1.1. Secondary endpoints included investigator-assessed (INV) confirmed ORR, INV duration of response (DOR), INV progression-free survival (PFS), and OS. Safety and tolerability were assessed.
Results
At data cutoff (Jun 16, 2023), 95 pts were enrolled (intent-to-treat [ITT]); 73 pts were confirmed HER2-positive (IHC 3+ or IHC 2+/ISH+; full analysis set [FAS]) by central laboratory. In the FAS, 65.8% of pts were <65 years of age, 72.6% were IHC 3+ and primary tumor location in 30.1% of pts was GEJ. Efficacy and safety data are shown in table.
Conclusions
This primary analysis of T-DXd in Chinese pts with HER2-positive advanced GC/GEJA demonstrated clinically meaningful and durable objective responses, with a manageable safety profile, and is consistent with results from DG01. Table: 172P
NCT04989816.
197P-Treatment patterns and clinical outcomes of patients with unresectable advanced or metastatic (UAM) gastric/gastroesophageal junction adenocarcinoma (GC/GEJA) in China: A multicenter real-world study
Background
This study aimed to investigate characteristics, treatment patterns and clinical outcomes of Chinese patients with UAM GC/GEJA in real-world settings.
Methods
This was a multicenter, retrospective, observational study using electronic medical records from four tertiary hospitals. Adult patients who were diagnosed with UAM GC/GEJA between Jan 1, 2017 and Dec 31, 2020 and had ≥1 inpatient admission related to UAM GC/GEJA from diagnosis to Aug 31, 2021 were included. Descriptive statistics were applied to summarize the data and Kaplan- Meier method was used to describe duration of treatment (DoT) and progression-free survival (PFS) by each line of therapy.
Results
Of the 2,745 eligible patients (median age 62 years, 69.2% male), 97.3% had a diagnosis of GA, 94.0% had stage IV disease, and 43.4% had peritoneum metastasis at diagnosis. Of the 2,745 patients, 1,902 (69.3%) received first-line (1L) therapy. Of the 1,902 patients, 729 (38.3%) subsequently received second-line (2L) therapy and 284 (14.9%) received third-line (3L) therapy. The majority of patients received chemotherapy alone in 1L and 2L settings (84.1% in 1L, 63.6% in 2L, 41.4% in 3L). Targeted therapy-based regimen (13.7% in 1L, 30.3% in 2L, 49.2% in 3L) and immunotherapy-based regimen (3.1% in 1L, 8.7% in 2L, 18.5% in 3L) were used more often in 3L setting. The most frequently used treatment regimen in 1L, 2L, and 3L were fluoropyrimidine (FP) plus platinum (44.5%), FP plus taxanes (16.5%), and anti-angiogenic tyrosine kinase inhibitors alone (18.2%), respectively. Median (95% CI) DoT (4.4 months [4.2, 4.8] in 1L, 3.1 months [2.7, 3.6] in 2L, 2.4 months [2.0, 2.9] in 3L) and PFS (6.5 months [6.1, 6.9] in 1L, 4.2 months [3.7, 4.5] in 2L, 3.2 months [2.8, 3.7] in 3L) decreased progressively with each advancing line of therapy.
Conclusions
Patients treated in 1L and 2L mainly received chemotherapy alone at that time. DoT and PFS were generally short in all lines of therapy, which suggests the need for more effective new treatment options.
186P-Efficacy and safety of fruquintinib with nab-paclitaxel in advanced G/GEJ cancer after exposure to immune checkpoint inhibitors: A single-center prospective clinical trial
Background
Immune checkpoint inhibitors (ICIs) expanded choices of early-line therapies in advanced gastric (G)/gastro-esophageal junction (GEJ) cancer. In addition, it' s observed that early-line ICI therapy, compared to chemotherapy, could enhance the efficacy of VEGFR inhibitors with chemotherapy in late lines. This single-center prospective clinical trial was aimed to explore the efficacy and safety of fruquintinib with nab-paclitaxel as second-line in patients (pts) with G/GEJ cancer exposed to ICIs in early lines.
Methods
Pts with advanced G/GEJ cancer who had been exposed to ICIs before the second line were eligible. 42 pts would receive 100g/m2 nab-paclitaxel on day 1 and day 8 every 3 weeks, and 4mg fruquintinib from day 1 to day 14 every 3 weeks. Progression-free survival (PFS) was set as the primary endpoint. The Kaplan–Meier method would be used to evaluate time-to-event outcomes.
Results
Up to Aug 10, 2023, 25 pts had been enrolled, 23 of whom were evaluable. 14 (60.9%) pts in evaluable set were male. All these pts was with stage Ⅳ of TNM staging. The median age was 58 (range: 33-74), and 6 (26.1%) pts were elder than 65 yr. 12 (63.2%) pts were with PD-L1 CPS greater than 1, 9 (47.4%) pts greater than 5, and 4 (17.4%) pts greater than 10. PD-L1 CPS of 4 pts was unknown. The pts had received a median of 5 (range: 1-20) cycles in early-line ICI therapy. 17 (73.9%) pts suffered metastasis in retroperitoneal lymph node and 7 (30.4%) pts in liver. With a median follow up time of 5.6 (range: 2.1-16.6) mo, the PFS achieved 4.8 (95% CI: 4.6-NA) mo. Despite the immatureness of overall survival (OS), the 1-year OS rate was 56.25% (95% CI: 17.27%-95.23%). The ORR was 47.8% (n=11), and DCR was 100% (n=23). As to safety, the most common (≥20%) AEs of all grades were white blood cell decrease, peripheral sensory neuropathy, and neutrophil count decrease, while that of grade≥3 was white blood cell decrease.
Conclusions
Fruquintinib with nab-paclitaxel as second-line therapy demonstrated good efficacy and safety in advanced G/GEJ cancer after exposure to ICIs. ICIs might increase benefit from this therapy, which warrants further investigations in a large cohort.
Clinical trial identification
ChiCTR2200059976.
https://cslide.ctimeetingtech.com/asia2023/attendee/confcal_1/presentation
