PO.PR01.01 · 预防研究

临床结局的决定因素：71项评估转移性结直肠癌的I期临床试验汇总分析

Determinants of clinical outcomes: A pooled analysis of 71 phase I clinical trials evaluating metastatic colorectal cancer

编号 2369 展板 5 时间 4/20 09:00–12:00 区域 Section 37 主讲 Ahan Bhatt, MBBS

分会场 Cancer Disparities

查看 PDF 下载 PDF 🔒 查看 / 下载完整 PDF 需登录并开通下载套餐 · 查看套餐 / 开通 AACR 官方页面

作者与单位 Authors & Affiliations

Ahan Bhatt¹, Hasan Zaidi², Shobi Venkatachalam³, Lawanya Singh², Abhiraj Saxena², Radha Patel³, Christina Boatwright³, Demmie Aguilar³, Jay Shah³, Mohammad Ghalib³, Imran Chaudhary⁴, Simran Goel⁴, Radhashree Maitra⁴, Eugenia Girda⁵, Sanjay Goel⁵

¹Department of Internal Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY,²Department of Internal Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ,³Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ,⁴Montefiore Medical Center, Bronx, NY,⁵Rutgers Cancer Institute of New Jersey, New Brunswick, NJ

摘要 Abstract

中文摘要

背景：少数族裔患者在临床试验中历来代表性不足。他们的临床结局往往在药物获批后回顾性评估，导致对包括转移性结直肠癌（mCRC）患者在内的更广泛人群疗效存在不确定性。在mCRC的I期试验中，患者选择标准仍具挑战性，客观的临床和实验室标志物可能改善统一筛查和结局预测。方法：我们回顾性审查了两家机构在1999—2018年和2021—2025年间入组I期试验的mCRC患者的病历。收集的数据包括人口统计学、临床和实验室检查结果、治疗反应和总生存期（OS）。变量采用机构或临床相关切点进行二分类。OS定义为从首剂日期至死亡或末次随访（若存活则删失）。采用Mantel-Cox检验（Prism GraphPad v10）进行单因素分析，报告风险比（HR）和95%置信区间（CI）。结果：我们分析了71项试验中的295例患者。中位年龄59岁（范围29—83岁）。50.5%的患者为女性。24.4%为非西班牙裔黑人（NHB），24.4%为西班牙裔，6.1%为亚裔，43.0%为非西班牙裔白人（NHW）。OS为9个月，不同种族/族裔之间无显著差异（p=0.71）。试验中位持续时间为59天（范围54—65天）。既往治疗线数中位数为3（范围0—11），转移部位数中位数为3（范围0—10）。在单因素模型中，体能状态差（PS≥2；HR 2.665，p=0.0026）、≥3个转移部位（HR 1.497，p=0.0049）和>3线既往治疗（HR 1.358，p=0.0167）与OS下降相关。实验室标志物包括低白蛋白（<3.9 g/dL；HR 1.596，p=0.0002）、高LDH（>281.5 U/L；HR 1.751，p<0.0001）、高CEA（>119.5 ng/mL；HR 1.513，p=0.0031）、肝酶升高（AST>40 U/L，HR 1.696，p=0.0004；ALP>150 U/L，HR 2.102，p<0.0001）、胆红素升高（≥1 mg/dL；HR 1.852，p=0.0204）和血细胞减少（WBC<6 K/μL，HR 0.66，p=0.0011；ANC<4 K/μL，HR 0.63，p=0.0004；血红蛋白<11.5 g/dL，HR 1.435，p=0.0043）也预测更差的OS。结论：mCRC患者无论年龄、性别或种族/族裔，在I期研究中结局相似。OS与既往治疗暴露相似的已发表数据相当。既往治疗充分、体能状态低下及转移扩散至>3个部位均与生存下降相关。高LDH和高CEA以及肝功能检查是关键参数，可能有助于优化早期mCRC研究的入选资格和分层。将展示一项多因素分析，探讨这些关键临床发现之间的相互作用。

查看英文原文 English abstract

Background: Minority patients are historically underrepresented in clinical trials. Their clinical outcomes are often reviewed retrospectively after drug approval, leaving uncertainty about efficacy in the broader population, including patients with metastatic colorectal cancer (mCRC). In phase I trials for mCRC, patient selection criteria remain challenging, and objective clinical and laboratory markers may improve uniform screening and outcome prediction. Methods: We retrospectively reviewed medical records of patients with mCRC enrolled in phase I trials at two institutions between 1999-2018 and 2021-2025. Data collected included demographics, clinical and laboratory findings, treatment responses, and overall survival (OS). Variables were dichotomized using institutional or clinically relevant cutoffs. OS was defined from the date of first dose to death or last follow-up (censored if alive). Univariate analyses were performed using the Mantel-Cox test (Prism GraphPad v10), with hazard ratios (HRs) and 95% confidence intervals (CIs) reported. Results: We analyzed 295 patients across 71 trials. Median age was 59 years (range, 29-83 years). 50.5% of patients were female. 24.4% were Non-Hispanic Black (NHB), 24.4% Hispanic, 6.1% Asian, 43.0% Non-Hispanic White (NHW). OS was 9 months and did not differ significantly among the different races/ethnicities (p = 0.71). The median duration on the trial was 59 days (range, 54-65 days). Median number of prior lines of therapy was 3 (range, 0-11), and the median number of sites of metastasis was 3 (range, 0-10). In a univariate model, poor performance status (PS ≥2; HR 2.665, p=0.0026), ≥3 metastatic sites (HR 1.497, p=0.0049), and > 3 prior lines of therapy (HR 1.358, p=0.0167) were associated with decreased OS. Laboratory markers including low albumin (<3.9 g/dL; HR 1.596, p=0.0002), high LDH (>281.5 U/L; HR 1.751, p<0.0001), high CEA (>119.5 ng/mL; HR 1.513, p=0.0031), elevated liver enzymes (AST>40 U/L, HR 1.696, p=0.0004; ALP>150 U/L, HR 2.102, p<0.0001), elevated bilirubin (≥1 mg/dL; HR 1.852, p=0.0204), and cytopenias (WBC<6 K/µL, HR 0.66, p=0.0011; ANC<4 K/µL, HR 0.63, p=0.0004; hemoglobin <11.5 g/dL, HR 1.435, p=0.0043) also predicted worse OS. Conclusion: Patients with mCRC, regardless of age, sex, or race/ethnicity, had similar outcomes in phase I studies. The OS was at par with published data with similar exposure to prior therapies. Heavily pre-treated patients, low performance status, and spread to >3 sites were all associated with decreased survival. High LDH and high CEA, along with liver function tests, are key parameters and may refine eligibility and stratification in early-phase mCRC studies. A multivariate analysis will be presented, looking into the interplay of these key clinical findings.

利益披露 Disclosure

A. Bhatt, None.. H. Zaidi, None.. S. Venkatachalam, None.. L. Singh, None.. A. Saxena, None.. R. Patel, None.. C. Boatwright, None.. D. Aguilar, None.. J. Shah, None.. M. Ghalib, None.. I. Chaudhary, None.. S. Goel, None.. R. Maitra, None.. E. Girda, None.

← 返回 AACR 2026 检索