Francesca Sarno, Jair Tenorio, Sofia Perea, Laura Medina, Roberto Pazo-Cid, Ignacio Juez, Rocio Garcia-Carbonero, Jaime Feliu, Carmen Guillen-Ponce, Pedro P. Lopez-Casas, Carmen Guerra, Yolanda Duran, Jose Francisco López-Acosta, Carolina Alonso, Estrella Esquivel, Ana Dopazo, Dipikaa Akshinthala, Senthil K. Muthuswamy, Pablo Lapunzina, Bruno Bockorny, Manuel Hidalgo
{"title":"A Phase III Randomized Trial of Integrated Genomics and Avatar Models for Personalized Treatment of Pancreatic Cancer: the AVATAR Trial","authors":"Francesca Sarno, Jair Tenorio, Sofia Perea, Laura Medina, Roberto Pazo-Cid, Ignacio Juez, Rocio Garcia-Carbonero, Jaime Feliu, Carmen Guillen-Ponce, Pedro P. Lopez-Casas, Carmen Guerra, Yolanda Duran, Jose Francisco López-Acosta, Carolina Alonso, Estrella Esquivel, Ana Dopazo, Dipikaa Akshinthala, Senthil K. Muthuswamy, Pablo Lapunzina, Bruno Bockorny, Manuel Hidalgo","doi":"10.1158/1078-0432.ccr-23-4026","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"5 1","pages":""},"PeriodicalIF":10.0000,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Cancer Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1158/1078-0432.ccr-23-4026","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
Clinical Cancer Research is a journal focusing on groundbreaking research in cancer, specifically in the areas where the laboratory and the clinic intersect. Our primary interest lies in clinical trials that investigate novel treatments, accompanied by research on pharmacology, molecular alterations, and biomarkers that can predict response or resistance to these treatments. Furthermore, we prioritize laboratory and animal studies that explore new drugs and targeted agents with the potential to advance to clinical trials. We also encourage research on targetable mechanisms of cancer development, progression, and metastasis.