KRAS Mutation Subtypes Associated with Different Survival Times in Pancreatic Cancer

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(ChemotherapyAdvisor) – Specific KRAS mutation subtypes are associated with poorer overall survival (OS) times among patients with unresectable pancreatic cancer (PC), according to a retrospective analysis of medical records published in the Journal of Gastroenterology.

KRAS mutation status and subtypes may be associated with survival duration in pancreatic cancer patients,” reported Takeshi Ogura, MD, of the Aichi Cancer Center Hospital's Department of Gastroenterology in Nagoya, Japan, and coauthors.

G12D or G12R subtypes of KRAS mutations were “negative prognostic factors” for OS (HR 1.60 [95% CI: 1.11-2.28]), they reported.

KRAS mutations in general are known to be prognostic biomarkers, but “only a few analyses of KRAS mutation subtypes have been published,” and no previously published studies presented analyses for unresectable pancreatic cancer, the authors noted.

They analyzed the medical records of 242 patients diagnosed with unresectable pancreatic cancer who had undergone endoscopic ultrasound-guided fine-needle tumor aspiration and histological diagnosis. Multivariate analyses showed that 214 (88.4%) of the patients' pancreatic tumors had a KRAS mutation. G12D was the most common KRAS subtype, present in 92 patients (42.9%). The G12 V mutation was found in 85 patients (39.7%), and G12R was found in 17 patients (7.9%). Codon-61 mutations occurred in 5 patients, and codon-13 mutation was found in 1 patient; another 10 patients had “unknown KRAS mutations,” the authors reported.

Median OS was 261 days for the entire study population, but patients with wild-type (unmutated) tumor KRAS status lived significantly longer (median OS 479 days) than patients whose tumors harbored any KRAS mutations (OS 255 days; P=0.03). Different KRAS mutations were associated with significantly different survival times. Median OS for patients whose tumors had G12D mutations was 242 days; G12 V mutation-group patients had a median OS of 338 days; and G12R mutation-harboring tumors were associated with a median OS of 204 days (log-rank difference between these three groups: P<0.01).

“Patients who had the G12 V mutation had a significantly longer OS than patients with G12D (P=0.01) or G12R (P<0.01),” the authors reported.

“This study is the largest of its kind yet to be published,” they wrote. “Difference in the survival of PC patients cannot be completely explained on the basis of KRAS mutation status and subtype. However, (these) may be important factors associated with survival in PC patients.”


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