A study compared two standard first-line chemotherapy regimens for advanced Pancreatic Ductal Adenocarcinoma (PDAC): FOLFIRINOX (FFX) and Gemcitabine plus nab-paclitaxel (GnP), examining how genetic markers, including BRCA2 and Tumor Mutational Burden (TMB), affect outcomes. In the overall population, GnP showed a slight survival advantage over FFX, supporting its use as a standard first-line therapy. Patients who received GnP first followed by FFX lived longer than those treated in the reverse sequence, highlighting the importance of treatment order.
Among the small subset of patients with BRCA2 pathogenic variants, roughly 3–4% of the cohort, FFX was highly effective. These patients had higher response rates (66.7% vs. 31.5%) and longer survival when treated with FFX, whereas GnP was less effective for this group. The study noted that as long as patients received a platinum-containing therapy at some point, long-term survival outcomes were similar.
Patients with high Tumor Mutational Burden (TMB), representing 2.9% of the cohort, experienced significantly improved survival, largely due to immune checkpoint inhibitor therapy, with nearly half receiving immunotherapy. Overall, the study suggests that GnP is a strong first-line choice for most patients. However, comprehensive genomic profiling is crucial to identify the small proportion of patients with BRCA2 mutations or TMB-high tumors, ensuring they receive the most effective therapy—whether platinum-based chemotherapy or immunotherapy—for optimal outcomes.