Bevacizumab

After bevacizumab was approved, the BICC-C trial was amended, and an additional 117 patients were randomly assigned to receive FOLFIRI/bevacizumab or mIFL/bevacizumab.

After bevacizumab was approved, the BICC-C trial was amended, and an additional 117 patients were randomly assigned to receive FOLFIRI/bevacizumab or mIFL/bevacizumab.

Although the primary end point of PFS was not significantly different, patients who received FOLFIRI/bevacizumab had a significantly better OS (not yet reached with a median follow-up of 22.6 months vs. 19.2 months, P = .007).

Patients with previously untreated metastatic colorectal cancer were randomly assigned to either IFL or IFL/bevacizumab.[68][Level of evidence A1]

Patients with previously untreated metastatic colorectal cancer were randomly assigned to either IFL or IFL/bevacizumab.[68][Level of evidence A1]

The patients randomly assigned to IFL/bevacizumab experienced a significantly better PFS (10.6 months in the IFL/bevacizumab arm compared with 6.2 months in the IFL/placebo arm; HRdisease progression, 0.54; P < .001) and OS (20.3 months in the IFL/ bevacizumab arm compared with 15.6 months in the IFL/placebo arm; HRdeath , 0.66; P < .001).[68]

Despite the lack of direct data, in standard practice, bevacizumab was added to FOLFOX as a standard first-line regimen based on the results of the NCCTG-N9741 trial.[69] Subsequently, in a randomized phase III study, patients with untreated, stage IV, colorectal cancer were randomly assigned in a 2 × 2 factorial design to CAPOX versus FOLFOX-4, then to bevacizumab versus placebo. PFS was the primary end point.

Despite the lack of direct data, in standard practice, bevacizumab was added to FOLFOX as a standard first-line regimen based on the results of the NCCTG-N9741 trial.[69] Subsequently, in a randomized phase III study, patients with untreated, stage IV, colorectal cancer were randomly assigned in a 2 × 2 factorial design to CAPOX versus FOLFOX-4, then to bevacizumab versus placebo. PFS was the primary end point.

In this trial, 1,401 patients were randomly assigned, and the median PFS was 9.4 months for patients who received bevacizumab and 8.0 months for the patients who received placebo (HR, 0.83; 97.5% CI, 0.72–0.95; P = .0023).[70][Level of evidence B1]

Despite the lack of direct data, in standard practice, bevacizumab was added to FOLFOX as a standard first-line regimen based on the results of the NCCTG-N9741 trial.[69] Subsequently, in a randomized phase III study, patients with untreated, stage IV, colorectal cancer were randomly assigned in a 2 × 2 factorial design to CAPOX versus FOLFOX-4, then to bevacizumab versus placebo. PFS was the primary end point.

The median OS was 21.3 months for patients who received bevacizumab and 19.9 months for patients who received placebo (HR, 0.89; 97.5% CI, 0.76–1.03; P = .077).

Despite the lack of direct data, in standard practice, bevacizumab was added to FOLFOX as a standard first-line regimen based on the results of the NCCTG-N9741 trial.[69] Subsequently, in a randomized phase III study, patients with untreated, stage IV, colorectal cancer were randomly assigned in a 2 × 2 factorial design to CAPOX versus FOLFOX-4, then to bevacizumab versus placebo. PFS was the primary end point.

The median PFS (intention-to-treat analysis) was 8.0 months in the pooled CAPOX-containing arms versus 8.5 months in the FOLFOX-4-containing arms (HR, 1.04; 97.5% CI, 0.93–1.16), with the upper limit of the 97.5% CI being below the predefined noninferiority margin of 1.23.[70,71]

Despite the lack of direct data, in standard practice, bevacizumab was added to FOLFOX as a standard first-line regimen based on the results of the NCCTG-N9741 trial.[69] Subsequently, in a randomized phase III study, patients with untreated, stage IV, colorectal cancer were randomly assigned in a 2 × 2 factorial design to CAPOX versus FOLFOX-4, then to bevacizumab versus placebo. PFS was the primary end point.

The effect of bevacizumab on OS is likely to be less than what was seen in the original Hurwitz study.[68]

Investigators from the Eastern Cooperative Oncology Group randomly assigned patients who had progressed on 5-FU/leucovorin and irinotecan to either FOLFOX or FOLFOX /bevacizumab.

Investigators from the Eastern Cooperative Oncology Group randomly assigned patients who had progressed on 5-FU/leucovorin and irinotecan to either FOLFOX or FOLFOX /bevacizumab.

Patients randomly assigned to FOLFOX/bevacizumab experienced a statistically significant improvement in PFS (7.43 months vs. 4.7 months, HR, 0.61; P < .0001) and OS (12.9 months vs. 10.8 months, HR, 0.75; P = .0011).[72][Level of evidence A1]