Therapy in Colorectal Cancer（结肠直肠癌的靶向治疗）ppt课件.pptVIP

* KRAS mutations were identified using PCR on DNA from tumor sections collected in a phase III trial comparing panitumumab monotherapy to BSC in patients with mCRC. This trial investigated whether the effect of panitumumab on PFS differed by KRAS status (Amado et al 2008). * CRC; colorectal cancer; HR, hazard ratio; PFS, progression-free survival. PFS was significantly increased in the panitumumab arm versus BSC in the wild type KRAS group. * Patients were randomized to receive either cetuximab (400 mg/m2 initial dose then 250 mg/m2 over 46 hours) plus FOLFIRI or FOLFIRI alone (Van Cutsem et al 2007). * Response rate was significantly increased by the addition of cetuximab 46.9% vs 38.7% and PFS was also longer in the cetuximab arm with a one year PFS rate of 23% for the FOLIFIRI only arm compared to 34% with the addition of cetuximab (Van Cutsem et al. 2007). * * The hazard ratio for the KRAS wild type was 0.68 for PFS translating into a 32% reduced risk for progression in the cetuximab arm. The PFS for the cetuximab arm at 9.9 months was significantly higher than the PFS for the FOLFIRI arm alone at 8.7 months (Van Cutsem et al. 2008). * * There was no difference for the PFS in the KRAS mutant population between the two arms in the study. Patients were randomized to receive cetuximab and FOLFOX4 versus FOLFOX4 alone. Genomic data was isolated from tumor material from the study to determine best overall response and PFS time by KRAS mutation status (Bokemeyer et al 2008). * * Difference between arms in KRAS wt only Belt at point 0.5, thus small difference in medians but compelling Hazard Ratio. Median PFS was higher in the cetuximab arm for the KRAS wild type population. * * Difference between arms in KRAS mt only Cetuximab addition to FOLFOX in KRASmt more or less implausible, suggesting better PFS for treatment without cetuximab * * * PACCE investigated the benefit of adding panitumumab to either oxaliplatin/bevacizumab or irinotecan/bevacizumab as first l