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.[24]

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.[24]

Although the primary end point of PFS was not significantly different, patients who received FOLFIRI/bevacizumab had a significantly better OS (28.0 months vs. 19.2 months; P = .037; HR for death, 1.79; 95% CI, 1.12–2.88).

In the Hurwitz study, patients with previously untreated metastatic colorectal cancer were randomly assigned to either IFL or IFL/bevacizumab.[29]

In the Hurwitz study, patients with previously untreated metastatic colorectal cancer were randomly assigned to either IFL or IFL/bevacizumab.[29]

The patients randomly assigned to the IFL/bevacizumab arm 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).[29]

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 NCCTG-N9741.[21] Subsequently, in a randomized phase III study, 1,401 patients with untreated, stage IV colorectal cancer were randomly assigned in a 2 × 2 factorial design to CAPOX versus FOLFOX4, then to bevacizumab versus placebo. PFS was the primary end point.[30][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 NCCTG-N9741.[21] Subsequently, in a randomized phase III study, 1,401 patients with untreated, stage IV colorectal cancer were randomly assigned in a 2 × 2 factorial design to CAPOX versus FOLFOX4, then to bevacizumab versus placebo. PFS was the primary end point.[30][Level of evidence B1]

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).

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 NCCTG-N9741.[21] Subsequently, in a randomized phase III study, 1,401 patients with untreated, stage IV colorectal cancer were randomly assigned in a 2 × 2 factorial design to CAPOX versus FOLFOX4, then to bevacizumab versus placebo. PFS was the primary end point.[30][Level of evidence B1]

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 NCCTG-N9741.[21] Subsequently, in a randomized phase III study, 1,401 patients with untreated, stage IV colorectal cancer were randomly assigned in a 2 × 2 factorial design to CAPOX versus FOLFOX4, then to bevacizumab versus placebo. PFS was the primary end point.[30][Level of evidence B1]

The median PFS (intention-to-treat analysis) was 8.0 months in the pooled CAPOX-containing arms versus 8.5 months in the FOLFOX4-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.[30,31]

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 NCCTG-N9741.[21] Subsequently, in a randomized phase III study, 1,401 patients with untreated, stage IV colorectal cancer were randomly assigned in a 2 × 2 factorial design to CAPOX versus FOLFOX4, then to bevacizumab versus placebo. PFS was the primary end point.[30][Level of evidence B1]

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

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

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

Patients randomly assigned to FOLFOX/bevacizumab experienced a statistically significant improvement in PFS compared with patients assigned to FOLFOX alone (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).[32][Level of evidence A1]