Multicenter phase 3 trial of integrated genomics and avatar models for personalized treatment of pancreatic cancer

Advanced pancreatic ductal adenocarcinoma (aPDAC) has limited treatment options. The multicenter phase 3 AVATAR trial compared comprehensive precision medicine versus conventional treatment for aPDAC. The group with conventional treatment (arm A) was treated at discretion of the physician; patients in arm B underwent tumor biopsy for whole-exome sequencing (WES) and to generate avatar mouse models and organoids for phenotypic drug screening. WES was performed in 80.3% of patients in arm B, with potentially actionable mutations detected in 21.5%. Experimental models were generated in 19.8%. Of the patients treated in arm B, only 10.2% received personalized treatment; the others could not receive matched therapy because of rapid clinical deterioration, delays in obtaining study results, or the absence of actionable targets. The median progression-free survival was 3.8 versus 4.3 months and the median overall survival was 8.7 versus 8.6 months for the conventional and experimental arms, respectively. Among the patients who received personalised treatment, the median overall survival was 19.3 months. The authors conclude that personalized therapy was challenging to implement in most patients with PDAC, and that survival was improved in the subset of patients who did receive matched therapy.