Bevacizumab exposure beyond first disease progression in patients with metastatic colorectal cancer: analyses of the ARIES observational cohort study.
OBJECTIVE
This analysis from Avastin® Registries: Investigation of Effectiveness and Safety (ARIES) examined the association between exposure to bevacizumab after disease progression (PD) and postprogression survival (PPS) in bevacizumab-exposed metastatic colorectal cancer (mCRC) through the application of time-dependent and time-fixed analytical methods.


METHODS
Patients with mCRC who were treated with first-line bevacizumab and who survived first PD (PD1) were included. A time-dependent Cox regression model was fitted to assess the effect of cumulative bevacizumab exposure on PPS, while controlling for potential confounders. In addition to support findings from previous studies, a modified intent-to-treat (mITT) analysis compared PPS in patients who received bevacizumab beyond disease progression (BBP) with those who did not (No-BBP).


RESULTS
Of 1550 patients, 1199 survived PD1 and had a median PPS of 13.4 months. Cumulative bevacizumab exposure was associated with improved PPS (p = 0.0040). After adjusting for confounders, the hazard ratios (HRs) for PPS decreased, on average, by 1.2% (range, 1.1-1.3%) with each additional dose of bevacizumab. In the mITT analysis, the median PPS for BBP (n = 438) was 14.4 months vs 10.6 months with for No-BBP (n = 667). BBP was found to be independently associated with longer PPS in a multivariable Cox regression analysis (HR, 0.84; 95% confidence interval, 0.73-0.97). Protocol-specified adverse events suspected to be associated with bevacizumab occurred in 13.0% of patients with BBP.


CONCLUSIONS
This analysis supports the observation that bevacizumab exposure after PD1 is associated with longer PPS in mCRC.
Mayo Clinic, Medical Oncology, Rochester, MN, USA.
Axel
A
Grothey
E Dawn
ED
Flick
Allen L
AL
Cohn
Tanios S
TS
Bekaii-Saab
Johanna C
JC
Bendell
Mark
M
Kozloff
Nancy
N
Roach
Yong
Y
Mun
Susan
S
Fish
Herbert I
HI
Hurwitz
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D016016:Proportional Hazards Models; D015996:Survival Rate; D013997:Time Factors; D055815:Young Adult
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab
bevacizumab; colorectal cancer; cumulative exposure; observational study; pharmacoepidemiology; treatment beyond progression; treatment patterns