학술논문
The Frequency of Specific KRAS Mutations, and Their Impact on Treatment Choice and Survival, in Patients With Metastatic Colorectal Cancer
Original Article
Original Article
Document Type
Academic Journal
Author
Source
The Oncologist. October 2023, Vol. 28 Issue 10, pe902, 8 p.
Subject
Language
English
ISSN
1083-7159
Abstract
Implications for Practice Specific gene mutations, including KRAS, are linked to poor prognosis in metastatic colorectal cancer (mCRC) patients. We found that survival differs depending on the location of the [...]
Background: Patients with metastatic colorectal cancer (mCRC) and KRAS mutations have a poor prognosis, seemingly dependent on the location of the mutation. This multicenter, retrospective, cohort study assessed the frequency and prognostic value of specific KRAS mutation codon locations in mCRC patients, and survival outcomes in relation to treatment. Materials and Methods: Data from mCRC patients treated in 10 Spanish hospitals between January 2011 and December 2015 were analyzed. The main objective was to investigate (1) the impact of KRAS mutation location on overall survival (OS), and (2) the effect of targeted treatment plus metastasectomy and primary tumor location on OS in patients with KRAS mutations. Results: The KRAS mutation location was known for 337/2002 patients. Of these, 177 patients received chemotherapy only, 155 received bevacizumab plus chemotherapy, and 5 received anti-epidermal growth factor receptor therapy plus chemotherapy; 94 patients underwent surgery. The most frequent KRAS mutation locations were G12A (33.8%), G12D (21.4%), and G12V (21.4%). Compared with other locations, patients with a G12S mutation had the shortest median OS (10.3 [95% CI, 2.5-18.0] months). OS was longer in patients who underwent surgery versus those who did not, with a trend toward prolonged survival with bevacizumab (median OS 26.7 [95% CI, 21.8-31.7] months) versus chemotherapy alone (median OS 23.2 [95% CI, 19.4-270] months). Conclusion: These findings confirm that KRAS mutation location may predict survival outcomes in patients with mCRC, and suggest that pre-/ post-operative bevacizumab plus metastasectomy provides survival benefits in patients with KRAS mutations. Key words: colonic neoplasms; mutation; codon; genes (ras); prognosis.
Background: Patients with metastatic colorectal cancer (mCRC) and KRAS mutations have a poor prognosis, seemingly dependent on the location of the mutation. This multicenter, retrospective, cohort study assessed the frequency and prognostic value of specific KRAS mutation codon locations in mCRC patients, and survival outcomes in relation to treatment. Materials and Methods: Data from mCRC patients treated in 10 Spanish hospitals between January 2011 and December 2015 were analyzed. The main objective was to investigate (1) the impact of KRAS mutation location on overall survival (OS), and (2) the effect of targeted treatment plus metastasectomy and primary tumor location on OS in patients with KRAS mutations. Results: The KRAS mutation location was known for 337/2002 patients. Of these, 177 patients received chemotherapy only, 155 received bevacizumab plus chemotherapy, and 5 received anti-epidermal growth factor receptor therapy plus chemotherapy; 94 patients underwent surgery. The most frequent KRAS mutation locations were G12A (33.8%), G12D (21.4%), and G12V (21.4%). Compared with other locations, patients with a G12S mutation had the shortest median OS (10.3 [95% CI, 2.5-18.0] months). OS was longer in patients who underwent surgery versus those who did not, with a trend toward prolonged survival with bevacizumab (median OS 26.7 [95% CI, 21.8-31.7] months) versus chemotherapy alone (median OS 23.2 [95% CI, 19.4-270] months). Conclusion: These findings confirm that KRAS mutation location may predict survival outcomes in patients with mCRC, and suggest that pre-/ post-operative bevacizumab plus metastasectomy provides survival benefits in patients with KRAS mutations. Key words: colonic neoplasms; mutation; codon; genes (ras); prognosis.