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Wild-Type KRAS and BRAF Could Predict Response to Cetuximab in Chinese Colorectal Cancer Patients
Jing Gao1, Ting-Ting Wang, Jing-Wei Yu
1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing 100142, China.
Objective:
To analyze the relationship between KRAS, BRAF mutations and the response toCetuximab in Chinese colorectal cancer patients.
Methods:
A total of273 Chinese colorectal cancer patients were evaluated for KRAS and BRAF mutations by Sanger sequencing. Among them, 59 patients with metastatic colorectal cancer (mCRC) were treated with Cetuximab in combination with chemotherapy from August 2005 to July 2009. Statistical analysis was conducted to assess the relationship between KRAS, BRAF mutations and the response or survival of 59 mCRC patients.
Results:
KRAS and BRAF mutation rates were 38.5% (105/273) and 5.1% (14/273), respectively, and KRAS/BRAF mutations were mutually exclusive. Among 59 patients treated with Cetuximab plus chemotherapy, KRAS and BRAF mutations were identified in 11and 5 patients, respectively. The response rates and median progression-free survivals (PFS) in KRAS wild-type and mutant patients were 35.4% (17/48) vs. 9.1% (1/11) (P=0.054) and 153 days vs. 99 days (P=0.01), respectively.Also, the response rates and median PFS in BRAF wild-type and mutant patients were 37.2% (16/43) vs. 20% (1/5) (P=0.016) and 138 days vs. 90 days (P=0.036), respectively.
Conclusion:
Besides KRAS, assessing BRAF mutation should also be required to select patients eligible for Cetuximab. Further prospective evaluation in large samples should be performed to confirm these preliminary findings.
Insights
This study found that BRAF mutations, in addition to KRAS mutations, are important for predicting Cetuximab response in Chinese colorectal cancer patients. Assessing both mutations improves patient selection for this targeted therapy.
Area of Science:
- Oncology
- Genetics
- Pharmacogenomics
Background:
- Colorectal cancer (CRC) is a significant health concern globally.
- Cetuximab is a targeted therapy used for metastatic colorectal cancer (mCRC).
- KRAS mutations are known to predict Cetuximab resistance, but the role of other mutations is still under investigation.
Purpose of the Study:
- To investigate the association between KRAS and BRAF mutations and Cetuximab treatment outcomes in Chinese patients with colorectal cancer.
- To determine if BRAF mutation status can aid in selecting patients eligible for Cetuximab therapy.
Main Methods:
- Sanger sequencing was used to analyze KRAS and BRAF mutations in 273 Chinese colorectal cancer patients.
- A cohort of 59 mCRC patients received Cetuximab combined with chemotherapy.
- Statistical analyses were performed to correlate mutation status with treatment response and survival.
Main Results:
- KRAS and BRAF mutation rates were 38.5% and 5.1%, respectively, and were mutually exclusive.
- Patients with KRAS wild-type status showed a higher response rate (35.4%) and longer median progression-free survival (PFS) (153 days) compared to KRAS mutant patients (9.1% response, 99 days PFS).
- BRAF wild-type patients also demonstrated significantly better response rates (37.2% vs. 20%) and median PFS (138 days vs. 90 days) than BRAF mutant patients when treated with Cetuximab.
Conclusions:
- BRAF mutation status, similar to KRAS, is a crucial biomarker for predicting Cetuximab efficacy in colorectal cancer.
- Routine assessment of both KRAS and BRAF mutations is recommended for optimal patient selection for Cetuximab therapy.
- Further large-scale prospective studies are warranted to validate these findings.
