Impact of KRAS Mutations on Clinical Outcomes in Pancreatic Cancer Patients Treated with First-line Gemcitabine-Based Chemotherapy

Kim, Seung Tae; Lim, Do Hyoung; Jang, Kee-Taek; Lim, Taekyu; Lee, Jeeyun; Choi, Yoon-La; Jang, Hye-Lim; Yi, Jun Ho; Baek, Kyung Kee; Park, Se Hoon; Park, Young Suk; Lim, Ho Yeong; Kang, Won Ki; Park, Joon Oh

doi:10.1158/1535-7163.mct-11-0269

Cited by 145Pancreatic and Hepatic Oncology ResearchPancreatitis Pathology and TreatmentCholangiocarcinoma and Gallbladder Cancer Studies

Impact of KRAS Mutations on Clinical Outcomes in Pancreatic Cancer Patients Treated with First-line Gemcitabine-Based Chemotherapy

Kim, Seung Tae, Lim, Do Hyoung, Jang, Kee-Taek, Lim, Taekyu, Lee, Jeeyun, Choi, Yoon-La, Jang, Hye-Lim, Yi, Jun Ho +6 more·2011·Molecular Cancer Therapeutics

DOI 10.1158/1535-7163.mct-11-0269

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Abstract

Although erlotinib has become an important therapeutic option in addition to gemcitabine, the high frequency of KRAS mutations in pancreatic cancer probably limits the benefits. We retrospectively studied 136 pancreatic cancer patients with available formalin-fixed paraffin-embedded tumor blocks from 2003 to 2009 to understand the clinical significance of KRAS mutations in pancreatic cancer patients treated with gemcitabine-based chemotherapy. KRAS mutations were analyzed by sequencing codons 12, 13, and 61. In this study, 71 (52.2%) of the 136 pancreatic adenocarcinomas examined harbored a point mutation in codons 12 (n = 70) and 61 (n = 1) of KRAS. KRAS mutation was not associated with clinicopathologic parameters. Patients with KRAS mutations showed a worse response (11.3%) than those with wild-type KRAS (26.2%) and poor survival (mutant KRAS, 5.8 months vs. wild-type KRAS, 8.0 months; P = 0.001). Multivariate analysis revealed good prognostic factors for overall survival as well to moderately differentiated histology (P < 0.001; HR = 0.437, 95% CI: 0.301–0.634), locally advanced disease (P < 0.001; HR = 0.417, 95% CI: 0.255–0.681), response to first-line chemotherapy (P = 0.003; HR = 0.482, 95% CI: 0.297–0.780), and wild-type KRAS (P = 0.001; HR = 0.523, 95% CI: 0.355–0.770). However, the observed survival advantage is derived from the subgroup of patients treated with gemcitabine/erlotinib (9.7 vs. 5.2 months; P = 0.002), whereas no survival difference based on KRAS mutation status is obvious in the other subgroup of patients treated without erlotinib (7.0 vs. 7.0 months; P = 0.121). These results need to be further explored in upcoming prospective studies to provide a rationale for personalized medicine in pancreatic cancer. Mol Cancer Ther; 10(10); 1993–9. ©2011 AACR.

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In locally advanced and metastatic PDAC, KRAS mutation has been found either negatively associated or not associated with survival with chemotherapy.
“In locally advanced and metastatic PDACs, KRAS mutation was found to be either negatively associated with or not associated with survival with chemotherapy (61, 62).”
From KRAS mutation in pancreatic cancer (2021) · cites this paper as [61]
There seems to be a consensus that KRAS mutation negatively influences response to EGFR-targeted therapy.
“There seems to be a consensus that KRAS mutation negatively influences response to EGFR-targeted therapy (61, 63).”
From KRAS mutation in pancreatic cancer (2021) · cites this paper as [61]

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Authors: Kim, S. T., Lim, D. H., Jang, K.-T., Lim, T., Lee, J., Choi, Y.-L., Jang, H.-L., Yi, J. H., Baek, K. K., Park, S. H., Park, Y. S., Lim, H. Y., Kang, W. K., & Park, J. O.
Affiliations: Samsung Medical Center (KR)
ORCID: Kim, Seung Tae
Jang, Kee-Taek
Choi, Yoon-La
Yi, Jun Ho
Park, Se Hoon
Park, Young Suk
Lim, Ho Yeong
Kang, Won Ki
Park, Joon Oh
Venue: Molecular Cancer Therapeutics
Publisher: American Association for Cancer Research (AACR)
Published: 2011-10-01
Volume: 10
Issue: 10
Pages: 1993-1999
ISSN: 1535-7163 (ISSN-L)
1538-8514
DOI: 10.1158/1535-7163.mct-11-0269
OpenAlex: W2117808097
Cited by: 145
References: 26
Citations by year: 2026: 5 · 2025: 7 · 2024: 9 · 2023: 7 · 2022: 8 · 2021: 14 · 2020: 10 · 2019: 6 · 2018: 8 · 2017: 9 · 2016: 14 · 2015: 13 · 2014: 12 · 2013: 11 · 2012: 10
FWCI: 5.49
Type: journal article
Language: en
Open access: closed
Locations: Molecular Cancer Therapeutics (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
Keywords: KRAS mutation, pancreatic ductal adenocarcinoma, gemcitabine-based chemotherapy, first-line chemotherapy, erlotinib, overall survival, prognostic factors, tumor response, KRAS codon 12, histological differentiation, locally advanced disease, molecular biomarkers, drug resistance, EGFR tyrosine kinase inhibitors
MeSH terms: Erlotinib Hydrochloride, Gemcitabine, Aged, Antineoplastic Combined Chemotherapy Protocols, Deoxycytidine, Female, Humans, Middle Aged, Mutation, Pancreatic Neoplasms, Quinazolines, Genes, ras, Treatment Outcome, Carcinoma, Pancreatic Ductal

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Impact of KRAS Mutations on Clinical Outcomes in Pancreatic Cancer Patients Treated with First-line Gemcitabine-Based Chemotherapy

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