Comorbidity, age and overall survival in cetuximab-treated patients with advanced colorectal cancer (ACRC)--results from NCIC CTG CO.17: a phase III trial of cetuximab versus best supportive care.
BACKGROUND
the interplay between comorbidity, age and performance status (PS) as predictors of outcome in advanced colorectal cancer (ACRC) is poorly understood. We examined these factors as predictors of treatment toxicity and outcome in cetuximab-treated patients with ACRC.


METHODS
comorbidity was independently evaluated using the Charlson Comorbidity Index (CCI), a validated measure of comorbidity based on the presence of medical conditions weighted according to their effect on mortality. CCI score was correlated with clinical and outcome data.


RESULTS
five hundred and seventy-two patients were included; 41% were ≥ 65 years and 25% had comorbidities at randomization. In multivariate analysis (MVA) of all covariates, only older age was associated with greater comorbidity (P = 0.008). Overall survival (OS) was significantly better for patients with greater comorbidity in univariate analysis (P = 0.047). Conversely, better PS was associated with better OS in MVA (hazard ratio 1.92 for PS = 2 versus PS = 0, P < 0.0001). Age was not associated with OS (P = 0.13). Elderly patients had significantly less grade ≥ 3 vomiting (P = 0.034) but more dyspnea (P = 0.005). Patients with greater comorbidity had significantly less grade ≥ 3 vomiting (P =  0.002) but more non-neutropenic fever (P = 0.005).


CONCLUSIONS
better PS was associated with improved OS. For patients with good PS, restricting cetuximab use in the setting of significant comorbidity does not appear justified.
Asmis
T R
TR
Department of Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada. Electronic address: tasmis@ottawahospital.on.ca.
Powell
E
E
Department of Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada.
Karapetis
C S
CS
Department of Medical Oncology, Flinders Medical Centre, Bedford Park, South Australia, Australia.
Jonker
D J
DJ
Department of Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada.
Tu
D
D
NCIC-Clinical Trials Group, Kingston, Ontario, Canada.
Jeffery
M
M
Oncology Department, Christchurch Hospital, Christchurch, New Zealand.
Pavlakis
N
N
Department of Medical Oncology, Royal North Shore Hospital, Sydney, New South Wales, Australia.
Gibbs
P
P
Department of Medical Oncology, Royal Melbourne and Western Hospital, Melbourne, Victoria, Australia.
Zhu
L
L
NCIC-Clinical Trials Group, Kingston, Ontario, Canada.
Dueck
D-A
DA
Department of Medical Oncology, Thunder Bay Regional Health Sciences Centre, Thunder Bay, Ontario, Canada.
Whittom
R
R
Department of Medical Oncology, Hopital du Sacre-Coeur de Montreal, Montreal, Quebec, Canada.
Langer
C
C
Bristol-Myers Squibb, Lawrenceville, NJ, USA.
O'Callaghan
C J
CJ
NCIC-Clinical Trials Group, Kingston, Ontario, Canada.
D000367:Age Factors; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000628:therapy*; D015897:Comorbidity; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D010166:Palliative Care / Q000379:methods*; D012307:Risk Factors; D015996:Survival Rate
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068818:Cetuximab