In a study reported in JAMA Network Open, Norton et al found that KRAS G12D and G12V mutations were associated with worse outcomes compared with KRAS wild-type in patients with metastatic pancreatic adenocarcinoma.
Study Details
The retrospective cohort study used data from a nationwide U.S.-based clinicogenomic database on 2,433 patients diagnosed with pancreatic adenocarcinoma between February 2010 and September 2022.
Key Findings
Among 2,023 patients with KRAS mutations, those with G12R mutation had the longest median time to new treatment (6.0 months, 95% confidence interval [CI] = 5.2–6.6 months) and longest median overall survival (13.2 months, 95% CI = 10.6–15.2 months).
Patients with KRAS G12D and G12V mutations had an increased risk of disease progression (HR = 1.15, 95% confidence interval [CI] = 1.04–1.29, P = .009; and HR = 1.16, 95% CI = 1.04–1.30, P = .01) and increased risk of death (HR = 1.29, 95% CI = 1.15–1.45, P < .001; and HR = 1.23, 95% CI = 1.09–1.39, P < .001) compared with those with wild-type KRAS.
Treatment with FOLFIRINOX (fluorouracil, irinotecan, oxaliplatin, and leucovorin) was associated with a significantly lower risk of disease progression and death vs gemcitabine with nab-paclitaxel (HR = 1.19, 95% CI = 1.09–1.29, P < .001; HR = 1.18, 95% CI = 1.07–1.29, P < .001) or without nab-paclitaxel (HR= 1.37, 95% CI = 1.11–1.69, P = .003; HR = 1.41, 95% CI = 1.13–1.75, P = .002).
The investigators concluded, “In this cohort study of 2,433 patients with [pancreatic adenocarcinoma], KRAS G12D and G12V mutations were associated with worse patient outcomes compared with KRAS wild type. KRAS G12R was associated with more favorable patient outcomes, and FOLFIRINOX was associated with better patient outcomes than gemcitabine-based therapies. These findings highlight the need for more effective systemic therapies for these groups of patients.”
Vaia Florou, MD, MS, of Huntsman Cancer Institute, University of Utah Health Care, Salt Lake City, is the corresponding author for the JAMA Network Open article.
Disclosure: The study was supported by the National Cancer Institute. For full disclosures of the study authors, visit jamanetwork.com.
