Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer: trial

Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer

N = 813

Population

Previously untreated metastatic colorectal cancer

Design

Randomised trial in previously untreated metastatic colorectal cancer. Patients received irinotecan, bolus fluorouracil and leucovorin (IFL) plus bevacizumab 5 mg per kilogram every two weeks, or IFL plus placebo. The primary endpoint was overall survival.

Primary endpoint

Arms

IFL plus placebo (control, n = 411): Irinotecan, bolus fluorouracil and leucovorin (IFL) plus placebo
IFL plus bevacizumab (experimental, n = 402): IFL plus bevacizumab 5 mg per kilogram every two weeks

People

Hurwitz H

OSHR 0.66Δ median OS+4.7 monthsPFSHR 0.54Δ median PFS+4.4 monthsΔ ORR+10 pointsDORHR 0.62

Show the numbers

Results reported for Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer
Endpoint	Analysis	IFL plus bevacizumab	IFL plus placebo	Effect
OSAll randomised patients (analysis population not stated in the abstract)	primaryHurwitz 2004	median 20.3 months	median 15.6 months	HR 0.66P<0.001The abstract gives no confidence interval for the hazard ratio for death.
PFSAll randomised patients (analysis population not stated in the abstract)	primaryHurwitz 2004	median 10.6 months	median 6.2 months	HR 0.54P<0.001Hazard ratio for disease progression; no confidence interval in the abstract.
ORRAll randomised patients (analysis population not stated in the abstract)	primaryHurwitz 2004	44.8%	34.8%	P=0.004
DORAll randomised patients (analysis population not stated in the abstract)	primaryHurwitz 2004	median 10.4 months	median 7.1 months	HR 0.62P=0.001Hazard ratio for progression of responding patients; no confidence interval in the abstract.

Results reported for Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer
Endpoint	Analysis	IFL plus bevacizumab	IFL plus placebo	Effect
OSAll randomised patients (analysis population not stated in the abstract)	primaryHurwitz 2004	median 20.3 months	median 15.6 months	HR 0.66P<0.001The abstract gives no confidence interval for the hazard ratio for death.
PFSAll randomised patients (analysis population not stated in the abstract)	primaryHurwitz 2004	median 10.6 months	median 6.2 months	HR 0.54P<0.001Hazard ratio for disease progression; no confidence interval in the abstract.
ORRAll randomised patients (analysis population not stated in the abstract)	primaryHurwitz 2004	44.8%	34.8%	P=0.004
DORAll randomised patients (analysis population not stated in the abstract)	primaryHurwitz 2004	median 10.4 months	median 7.1 months	HR 0.62P=0.001Hazard ratio for progression of responding patients; no confidence interval in the abstract.

Illustrative — modelled from reported values, not trial data. OS, primary.

Show curves

IFL plus placebo (control)
IFL plus bevacizumab (experimental)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	IFL plus placebo	IFL plus bevacizumab
0	100.0%	100.0%
13	56.1%	64.2%
25	32.9%	42.6%
38	18.5%	27.3%
51	10.4%	17.5%

Illustrative — modelled from reported values, not trial data. PFS, primary.

Show curves

IFL plus placebo (control)
IFL plus bevacizumab (experimental)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	IFL plus placebo	IFL plus bevacizumab
0	100.0%	100.0%
7	45.7%	63.3%
13	23.4%	42.7%
20	10.7%	27.0%
27	4.9%	17.1%

Appears in

2004 Bevacizumab added to first-line irinotecan-based chemotherapy

Sources

Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350(23):2335-42.
PubMed DOI