KRAS mutation detection by high-resolution melting analysis significantly predicts clinical benefit of cetuximab in metastatic colorectal cancer
British Journal of Cancer, 07/18/2012
Malapelle U et al. – High–resolution melting analysis identified 8% more KRAS–mutant (MUT) patients not responding to cetuximab–containing regimens, suggesting that high–resolution melting analysis (HRMA) may be more effective than direct sequencing in selecting patients for anti–EGFR antibodies.Methods
- The authors considered 50 mCRC patients scored as KRAS-WT by direct sequencing and treated with cetuximab-containing chemotherapy, and tested the correlations between HRMA findings and response rate (RR), progression-free (PFS) and overall survival (OS).
- Aberrant melting curves were detected in four (8%) cases; gene cloning confirmed these mutations.
- Response rate (RR) of HRMA KRAS-WT patients was 28.3%.
- There was no response in HRMA KRAS-MUT patients.
- Disease control rate (responsive plus stable disease) was 58.7% in HRMA KRAS-WT patients and 25% in HRMA KRAS-MUT patients.
- There was no correlation between HRMA KRAS status and RR (P=0.287) or disease control (P=0.219).
- Median PFS (4.8 vs 2.3months; hazard ratio (HR)=0.29, P=0.02) and OS (11.0 vs 2.7months; HR=0.11, P=0.03) were significantly longer for the HRMA KRAS-WT than for HRMA KRAS-MUT patients.