A Phase II Trial to Assess the Evolution of the KRAS Mutation Load by Liquid Biopsy in Patients With Resectable Pancreatic Ductal Adenocarcinoma Treated With Neoadjuvant NALIRIFOX

OBJECTIVES: To evaluate the association between the KRAS mutational load and the histologic tumor response in patients with resectable pancreatic ductal adenocarcinoma (PDAC) who received neoadjuvant treatment (NAC) with pegylated liposomal irinotecan in combination with oxaliplatin, 5-fluorouracil, and leucovorin (NALIRIFOX). METHODS: This was a multicenter, single-arm, interventional, open-label, phase 2 trial in patients 18 years or older who had histologically or cytologically confirmed PDAC and were candidates for surgery and received neoadjuvant NALIRIFOX. The primary outcome was determination of the association between the KRAS mutational load and the histologic tumor response after chemotherapy. RESULTS: Twenty patients were included in the study. Before initiating NAC, 11 patients were KRAS+, 6 were KRAS-, and 3 were not evaluable for KRAS mutation status. Eight of the 11 (72.7%) patients changed from KRAS+ at baseline to KRAS- after treatment, and none of the 6 (0.0%) patients changed from KRAS- at baseline to KRAS+ after treatment. A good histopathologic response after NAC was observed in 3 (15%) of the 20 patients, with a greater proportion of good responses among patients who were KRAS- (3 out of 16 [18.8%]) than among those who were KRAS+ (0 out of 1 [0.0%]) after NAC, although the differences were not statistically significant ( P =0.633). CONCLUSIONS: Our results indicate that patients with potentially resectable PDAC tend to have detectable KRAS in the blood if the disease is locally more advanced and that most patients who are treated with neoadjuvant NALIRIFOX are negative for KRAS at the end of therapy.