Precision medicine should be first-line treatment for metastatic pancreatic cancer, study finds

A new clinical trial comparing the efficacy of two treatments commonly used on patients with metastatic pancreatic cancer has shed new light on the importance of using genomic sequencing to inform care as early as possible, highlighting the value of precision oncology approaches to cancer treatment.  

Partially funded by the Marathon of Hope Cancer Centres Network, the PASS-01 trial is the first randomized study in North America to directly compare two standard first-line chemotherapy regimens for previously untreated metastatic pancreatic cancer: modified FOLFIRINOX (mFFX) and gemcitabine plus nab-paclitaxel (GnP). The trial not only evaluated clinical outcomes; enrolled patients also received comprehensive molecular profiling to better understand how tumour biology influences treatment response. 

“The two chemotherapy options showed quite similar value for patients who benefited, but overall outcomes remain poor with either treatment,” said Dr. Jennifer Knox, a clinician investigator at the Princess Margaret Cancer Centres in Toronto who led the research team. “What we did see was that GnP was generally quite better tolerated, without losing efficacy, which is an important consideration for patients facing an aggressive disease.” 

Patients with certain genomic characteristics did respond differently to first-line therapy, indicating that these characteristics may be biomarkers of therapy response. But for most patients, switching to the other therapy as a second-line treatment wasn’t possible as they were too frail or had succumbed to their disease. This delivered a critical insight: molecular profiling at diagnosis can provide valuable prognostic information and may help guide treatment selection—if it can be done quickly enough. 

“Despite all the advantages of trial participation, only about half of patients were well enough to receive second-line therapy,” said Dr. Knox. “That means the first-line decision is often the only real shot. The best ideas need to go first.” 

Published in the Journal of Clinical Oncology, the study demonstrated that precision oncology approaches can—and should—be applied at the very start of treatment for pancreatic cancer. Without early molecular characterization, opportunities to select the most effective chemotherapy or to match patients to targeted therapies and clinical trials may be lost. 

“PASS-01 shows that precision medicine in pancreatic cancer shouldn’t wait only for later lines of therapy,” said Dr. Knox. “If we don’t determine molecular features upfront and act on them as soon as possible, we may miss a critical window to improve outcomes.” 

In addition to its clinical findings, PASS-01 represents a major collaborative achievement. The trial brought together leading pancreatic cancer researchers across North America, each leading an important research question. The trial generated one of the most comprehensive datasets in the field—integrating clinical outcomes with molecular and biological data from each patient enrolled. Data generated in Canadian centres for this study were funded by the Network, meaning that they will also be part of the Gold Cohort and will help unlock future discoveries that accelerate precision oncology.   

“Academic-led trials like PASS-01 are essential for driving meaningful change that can eventually be implemented more broadly,” said Dr. Knox. “This is another example of how the Network is bringing cutting-edge treatments to more Canadian patients.”