Racial differences in advanced colorectal cancer outcomes and pharmacogenetics: a subgroup analysis of a large randomized clinical trial.
OBJECTIVE
Racial disparities in colorectal cancer (CRC) survival are documented, but there are few data on comparative response to chemotherapy. A subgroup analysis of a multisite National Cancer Institute-sponsored trial (N9741) was performed comparing outcomes of black and white patients with metastatic CRC receiving uniform treatment.


METHODS
Adverse events (AEs), response rate (RR), time to progression (TTP), overall survival (OS), and dose-intensity were examined as a function of self-reported race in 1,412 patients treated with irinotecan/fluorouracil, fluorouracil/oxaliplatin, or irinotecan/oxaliplatin. Pharmacogenetic analysis was performed on 486 patients with blood available for germline DNA analysis.


RESULTS
OS was 1.5 months shorter and TTP was 0.6 months shorter in black than white patients (OS: hazard ratio [HR] = 1.13; 95% CI, 0.90 to 1.42; TTP: HR = 0.91, 95% CI, 0.73 to 1.13); neither difference was statistically significant. RR was significantly higher in whites (41%) than blacks (28%; P = .008). Grade 3 or greater AEs were also higher in whites (48%) than blacks (34%; P = .004). These relationships were maintained in multivariate models adjusting for arm, age, sex, and performance status. There was no difference in dose-intensity of delivered therapy. Significant racial differences in prevalence of pharmacogenetic variants were observed, although small sample size precluded investigating the relationship between treatment, race, and genotype.


CONCLUSIONS
OS and TTP are similar in black and white patients treated per protocol with standardized therapy for metastatic CRC. However, RR and AEs vary considerably by race. The marked racial differences in relevant pharmacogenetics, a potential explanation for differing RR and AEs, are worthy of future study.
Sanoff
Hanna K
HK
Department of Medicine, Division of Hematology/Oncology, University of North Carolina, Chapel Hill, NC 27599-7305, USA.
Sargent
Daniel J
DJ
Green
Erin M
EM
McLeod
Howard L
HL
Goldberg
Richard M
RM
D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000208:ethnology* / Q000235:genetics / Q000401:mortality / Q000556:secondary; D004247:DNA / Q000097:blood; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D016016:Proportional Hazards Models; D018570:Risk Assessment; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics*; D055815:Young Adult
D009944:Organoplatinum Compounds; D004247:DNA; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin