Purpose: Pancreatic adenocarcinoma (PDAC) has limited treatment options. We compared the efficacy of comprehensive precision medicine against the conventional treatment in PDAC. Methods: Phase III trial of advanced PDAC where patients were randomized (1:2) to a conventional treatment treated at physician’s discretion (arm A), or to precision medicine (arm B). Subjects randomized to arm B underwent a tumor biopsy for whole exome sequencing (WES) and to generate avatar mouse models and patient derived organoids for phenotypic drug screening, with final treatment recommended by molecular tumor board. The primary objective was median overall survival (OS). Results: 137 patients were enrolled with 125 randomized, 44 to arm A and 81 to Arm B. WES was performed in 80.3% (65/81) patients of arm B, with potentially actionable mutations detected in 21.5% (14/65). Experimental models were generated in 16/81 patients (19.8%). Second-line treatment was administered to 39 patients in the experimental arm, but only 4 (10.2%) received personalized treatment, while 35 could not be receive matched therapy due to rapid clinical deterioration, delays in obtaining study results or absence of actionable targets. Median OS was 8.7 and 8.6 months (p=0.849) and median progression-free survival was 3.8 and 4.3 months (p=0.563) for the conventional and experimental arms, respectively. Notably, the four patients who received personalized treatment had median OS of 19.3 months. Conclusions: Personalized medicine was challenging to implement in most patients with PDAC, limiting the interpretation of intention to treat analysis. Survival was improved in the subset of patients who did receive matched therapy.

中文翻译：

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用于胰腺癌个性化治疗的综合基因组学和 Avatar 模型的 III 期随机试验：AVATAR 试验


目的：胰腺癌 （PDAC） 的治疗选择有限。我们比较了 PDAC 中综合精准医学与常规治疗的疗效。方法：晚期 PDAC 的 III 期试验，其中患者被随机分配 （1：2） 接受医生酌情治疗的常规治疗组 （A 组） 或精准医学组 （B 组）。随机分配到 B 组的受试者接受了全外显子组测序 （WES） 的肿瘤活检，并生成 avatar 小鼠模型和患者来源的类器官以进行表型药物筛选，最终治疗由分子肿瘤委员会推荐。主要目标是中位总生存期 （OS）。结果： 入组 137 例患者，其中 125 例随机分配，A 组 44 例，B 组 81 例，B 组 80.3% （65/81） 的患者进行 WES，21.5% （14/65） 检测到潜在可操作的突变。在 16/81 例患者 （19.8%） 中生成实验模型。实验组对 39 名患者进行了二线治疗，但只有 4 名 （10.2%） 接受了个性化治疗，而 35 名患者由于临床迅速恶化、延迟获得研究结果或缺乏可操作的靶点而无法接受匹配治疗。常规组和实验组的中位 OS 分别为 8.7 个月和 8.6 个月 （p=0.849），中位无进展生存期分别为 3.8 个月和 4.3 个月 （p=0.563）。值得注意的是，接受个性化治疗的 4 例患者的中位 OS 为 19.3 个月。结论： 在大多数 PDAC 患者中实施个性化医疗具有挑战性，限制了对意向治疗分析的解释。接受匹配治疗的患者子集的生存率有所提高。