58733
document
A randomized , placebo-controlled phase 2 study of ganitumab or conatumumab in combination with FOLFIRI for second-line treatment of mutant KRAS metastatic colorectal cancer . BACKGROUND Targeted agents presently available for mutant KRAS metastatic colorectal cancer ( mCRC ) are bevacizumab and aflibercept . We evaluated the efficacy and safety of conatumumab ( an agonistic monoclonal antibody against human death receptor 5 ) and ganitumab ( a monoclonal antibody against the type 1 insulin-like growth factor receptor ) combined with standard FOLFIRI chemotherapy as a second-line treatment in patients with mutant KRAS mCRC . PATIENTS AND METHODS Patients with mutant KRAS metastatic adenocarcinoma of the colon or rectum refractory to fluoropyrimidine- and oxaliplatin-based chemotherapy were randomized 1 : 1 : 1 to receive intravenous FOLFIRI plus conatumumab 10 mg/kg ( Arm A ) , ganitumab 12 mg/kg ( Arm B ) , or placebo ( Arm C ) Q2W . The primary end point was progression-free survival ( PFS ) . RESULTS In total , 155 patients were randomized . Median PFS in Arms A , B , and C was 6.5 months ( HR , 0.69 ; P = 0.147 ) , 4.5 months ( HR , 1.01 ; P = 0.998 ) , and 4.6 months , respectively ; median overall survival was 12.3 months ( HR , 0.89 ; P = 0.650 ) , 12.4 months ( HR , 1.27 ; P = 0.357 ) , and 12.0 months ; and objective response rate was 14 % , 8 % , and 2 % . The most common grade ≥3 adverse events in Arms A/B/C included neutropenia ( 30 % /25 % /18 % ) and diarrhea ( 18 % /2 % /10 % ) . CONCLUSIONS Conatumumab , but not ganitumab , plus FOLFIRI was associated with a trend toward improved PFS . Both combinations had acceptable toxicity .
58734
Intervention_Control
placebo-controlled
58735
Intervention_Pharmacological
ganitumab or conatumumab
58736
Intervention_Pharmacological
bevacizumab
58737
Intervention_Pharmacological
aflibercept .
58738
Intervention_Pharmacological
conatumumab
58739
Intervention_Pharmacological
ganitumab
58740
Intervention_Pharmacological
fluoropyrimidine- and oxaliplatin-based chemotherapy
58741
Intervention_Pharmacological
intravenous FOLFIRI plus conatumumab 10 mg/kg ( Arm A ) , ganitumab 12 mg/kg ( Arm B ) , or placebo
58742
Outcome_Other
efficacy
58743
Outcome_Other
safety
58744
Outcome_Mortality
progression-free survival ( PFS ) .
58745
Outcome_Mortality
Median PFS
58746
Outcome_Mortality
median overall survival
58747
Outcome_Other
objective response rate
58748
Participant_Condition
mutant KRAS metastatic adenocarcinoma of the colon or rectum refractory
58749
Participant_Sample-size
155