PO.RSP01.01 · 监管科学与政策

活检要求对癌症I期试验患者入组的影响

Effect of biopsy requirement on patient enrollment to phase I trials in cancer

编号 1394 展板 3 时间 4/20 09:00–12:00 区域 Section 2 主讲 Catherine Yang, BA

分会场 Regulatory Science and Policy

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作者与单位 Authors & Affiliations

Catherine Yang¹, Mona Yuan¹, Sebastian Saenz¹, Marisa Palmeri¹, Mohammad Ghalib², Dina Oz², Diana Nelson², Rita M. Musanti², Devika Rao³, Eugenia Girda², Francis Kang¹, Sanjay Goel²

¹Robert Wood Johnson Medical School, New Brunswick, NJ,²Rutgers Cancer Institute of New Jersey, New Brunswick, NJ,³Memorial Sloan Kettering Cancer Center, New York, NY

摘要 Abstract

中文摘要

背景：临床试验近来的一个趋势是要求进行活检（Bx），有时为强制性。主要原因是为了更好地理解癌症生物学的药效动力学效应。我们试图确定活检要求在这一弱势人群中是否有任何不利影响。方法：我们纳入了2022年6月至2025年8月在一所NCI指定的综合癌症中心入组I期试验的患者（pts）。收集的数据包括性别、种族、年龄、体重指数（BMI），知情同意/治疗开始/末次给药/停止治疗/末次联系/死亡的日期，血清化验值，既往治疗次数，转移部位，以及活检部位/入路/并发症。一名介入放射科医生复核影像以评估安全性，将认为合适的靶点在影像引导下进行活检。结局采用Prism GraphPad v10中的Mantel-Cox检验进行分析。结果：228名患者[男性（n=104，45.6%）]，年龄60.5岁，23–82岁（中位数，范围），非西班牙裔白人130人（57%）、非西班牙裔黑人37人（16.2%）、西班牙裔34人（14.9%）、亚裔27人（11.8%），同意参与25项临床试验。其中，8项为强制配对肿瘤活检，15项为强制或可选活检，2项不要求活检。最常见的诊断为结直肠癌（54人，23.7%）、胰腺癌（29人，12.7%）、其他消化道肿瘤（26人，11.4%）、肺癌（18人，7.9%）、乳腺癌（12人，5.3%）、前列腺癌（5人，2.2%）及其他（84人，36.8%）。影像引导包括超声74例（57.8%）、CT扫描49例（38.3%）及其他5例（3.9%）。总体而言，91名（39.9%）患者提供了128份活检样本；37份为配对活检，49份仅为给药前活检，5份仅为研究中活检。5名患者因被认为不安全/高风险而未接受活检。活检部位包括肝脏63例（49.2%）、肺13例（10.2%）、淋巴结15例（11.7%）、腹膜8例（6.3%）、骨1例（0.8%）及其他28例（21.9%）。2名患者出现气胸并康复，无后遗症。从知情同意到开始研究治疗的中位时长在活检患者中为18.5天，非活检患者中为14天（p=0.001）。研究期间的中位时长在活检患者中为62天，非活检患者中为66.5天（p=0.08）。总生存期（OS），以从首次给药到死亡/末次随访的时间计算，活检患者为123天，非活检患者为163天（p=0.049）。在单变量模型中，性别（男性/女性；HR 1.37；p=0.02）、白蛋白（高/低，HR 0.47，p=0.0001）、中性粒细胞-淋巴细胞比值（低/高，HR 0.68，p=0.003）、血红蛋白（高/低，HR 0.71，p=0.01）、BMI（高/低，HR 0.72，p=0.02）以及AST（高/低，HR 0.68，p=0.004）具有显著性，而年龄、种族/族裔、总胆红素、血小板、ALT、转移部位数和既往治疗线数则不显著。结论：进入I期试验的患者中有40%接受了研究特定活检，其接受首剂研究药物的时间中位延迟4.5天，OS降低41天。将展示多变量建模，以充分理解活检患者OS受损这一耐人寻味的观察结果。

查看英文原文 English abstract

Background: A recent trend in clinical trials is the requirement of biopsies (Bx), sometimes mandatory. The main reason is to better understand cancer biology pharmacodynamic effect. We sought to determine whether the requirement for Bx among this vulnerable population had any detrimental effect. Methods: We included patients (pts) enrolled in phase I trials from June 2022-August 2025 at a single NCI-designated comprehensive cancer center. Data collected included sex, race, age, body mass index (BMI), dates of consent/treatment start/last dose/off treatment/last contact/death, serum lab values, number of prior treatments, metastatic sites, and Bx site/approach/complications. An interventional radiologist reviewed images to assess safety, with targets deemed appropriate biopsied under image guidance. Outcomes were analyzed by Mantel-Cox test in Prism GraphPad v10. Results: 228 pts [male (n=104, 45.6%)], age 60.5, 23-82 (median, range), NHW-130 (57%), NHB-37 (16.2%), Hispanic-34 (14.9%), and Asian-27 (11.8%) consented to 25 clinical trials. Of these, 8 were mandated paired tumor Bx, 15 mandatory or optional Bx, and 2 did not require Bx. The most common diagnoses were colorectal (54, 23.7%), pancreas (29,12.7%), other GI (26, 11.4%), lung (18, 7.9%), breast (12, 5.3%), prostate (5, 2.2%), and others (84, 36.8%). Image guidance included ultrasound 74 (57.8%), CT scans 49 (38.3%), and others 5 (3.9%). Overall, 91 (39.9%) pts provided 128 Bx samples; 37 paired Bx, 49 only pre-dose Bx, and 5 only on-study Bx. Five pts did not undergo Bx because it was deemed unsafe/high risk. Sites of Bx included liver 63 (49.2%), lung 13 (10.2%), lymph node 15 (11.7%), peritoneum 8 (6.3%), bone 1 (0.8%), and others 28 (21.9%). Two patients developed pneumothorax and recovered without sequelae. The median duration from consent to start of study treatment was 18.5 days among Bx pts vs. 14 among non Bx pts (p = 0.001). The median duration of time on study was 62 days among Bx pts vs. 66.5 days among non Bx pts (p = 0.08). The overall survival (OS), calculated as time from first dose of treatment to death/last follow up, was 123 days among Bx pts and 163 days among non Bx pts (p = 0.049). In a univariable model, sex (males/women; HR 1.37; p=0.02), albumin (high/low, HR 0.47, p=0.0001), neutrophil-lymphocyte ratio (low/high, HR 0.68, p=0.003), hemoglobin (high/low, HR 0.71, p=0.01), BMI (high/low, HR 0.72, p=0.02), and AST (high/low, HR 0.68, p=0.004), were significant, while age, race/ethnicity, total bilirubin, platelet, ALT, # sites of metastases, and # prior lines of therapy were not. Conclusions: 40% of pts entering phase I trials underwent study specific Bx, had a median delay of 4.5 days in receiving the first dose of study medication and experienced lower OS by 41 days. Multivariable modeling will be presented to fully understand the intriguing observation of a compromise in OS among patients who underwent biopsies.

利益披露 Disclosure

C. Yang, None.. M. Yuan, None.. S. Saenz, None.. M. Palmeri, None.. M. Ghalib, None.. D. Oz, None.. D. Nelson, None.. R. M. Musanti, None.. D. Rao, None.. E. Girda, None.. F. Kang, None.

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