FDA Approves Aflibercept for Advanced Colorectal Cancer

Aflibercept, an angiogenesis inhibitor, has been approved as a second-line treatment for metastatic colorectal cancer in combination with the FOLFIRI chemotherapy regimen, the Food and Drug Administration announced on Aug. 3.

The indication is for patients whose tumors are resistant to, or have progressed after, an oxaliplatin-containing chemotherapy regimen, according to the FDA statement. The FOLFIRI regimen comprises folinic acid (leucovorin), 5-fluorouracil, and irinotecan.

Approval was based on the phase III VELOUR study of 1,226 patients with metastatic colorectal cancer whose disease progressed during treatment with oxaliplatin-based combination chemotherapy or whose tumor was surgically removed but recurred within 6 months after treatment with oxaliplatin-based combination chemotherapy. Patients continued treatment until cancer progression or unacceptable adverse effects.

The addition of aflibercept was associated with improvements in median overall survival and response rate and with a delay in tumor progression and growth: Overall survival reached a median of 13.5 months among those treated with aflibercept and FOLFIRI, vs. 12 months among those treated with placebo and FOLFIRI. Tumor size was reduced in 20% of those on the combination regimen and 11% of those receiving FOLFIRI plus placebo. In addition, median progression-free survival among patients given aflibercept and FOLIRI was 6.9 months, compared with 4.7 months in the placebo group.

Leucopenia, diarrhea, mouth ulcers, fatigue, hypertension, proteinuria, weight loss, decreased appetite, abdominal pain, and headache were among the most common side effects associated with treatment. A boxed warning covers the increased risk of severe and sometimes fatal bleeding, including gastrointestinal bleeding, GI perforations, and impaired wound healing.

Aflibercept targets the vascular endothelial growth factor (VEGF) and is also referred to as VEGF Trap. It will be marketed as Zaltrap by Sanofi-Aventis in collaboration with Regeneron Pharmaceuticals.

Another VEGF-specific angiogenesis inhibitor, bevacizumab (Avastin), was previously approved as a first- or second- line treatment of patients with metastatic colorectal cancer, in combination with intravenous 5-fluorouracil–based chemotherapy.

"This approval demonstrates the benefits of adding a biological agent, Zaltrap, to a commonly used chemotherapy drug regimen, FOLFIRI," Dr. Richard Pazdur, director of the office of hematology and oncology products in the FDA’s Center for Drug Evaluation and Research, Silver Spring, Md., said in the FDA announcement.

Click here to see a discussion of the VELOUR trial results in the journal Community Oncology.

Click here for prescribing information from the FDA.

Aflibercept, an angiogenesis inhibitor, has been approved as a second-line treatment for metastatic colorectal cancer in combination with the FOLFIRI chemotherapy regimen, the Food and Drug Administration announced on Aug. 3.

The indication is for patients whose tumors are resistant to, or have progressed after, an oxaliplatin-containing chemotherapy regimen, according to the FDA statement. The FOLFIRI regimen comprises folinic acid (leucovorin), 5-fluorouracil, and irinotecan.

Approval was based on the phase III VELOUR study of 1,226 patients with metastatic colorectal cancer whose disease progressed during treatment with oxaliplatin-based combination chemotherapy or whose tumor was surgically removed but recurred within 6 months after treatment with oxaliplatin-based combination chemotherapy. Patients continued treatment until cancer progression or unacceptable adverse effects.

The addition of aflibercept was associated with improvements in median overall survival and response rate and with a delay in tumor progression and growth: Overall survival reached a median of 13.5 months among those treated with aflibercept and FOLFIRI, vs. 12 months among those treated with placebo and FOLFIRI. Tumor size was reduced in 20% of those on the combination regimen and 11% of those receiving FOLFIRI plus placebo. In addition, median progression-free survival among patients given aflibercept and FOLIRI was 6.9 months, compared with 4.7 months in the placebo group.

Leucopenia, diarrhea, mouth ulcers, fatigue, hypertension, proteinuria, weight loss, decreased appetite, abdominal pain, and headache were among the most common side effects associated with treatment. A boxed warning covers the increased risk of severe and sometimes fatal bleeding, including gastrointestinal bleeding, GI perforations, and impaired wound healing.

Aflibercept targets the vascular endothelial growth factor (VEGF) and is also referred to as VEGF Trap. It will be marketed as Zaltrap by Sanofi-Aventis in collaboration with Regeneron Pharmaceuticals.

Another VEGF-specific angiogenesis inhibitor, bevacizumab (Avastin), was previously approved as a first- or second- line treatment of patients with metastatic colorectal cancer, in combination with intravenous 5-fluorouracil–based chemotherapy.

"This approval demonstrates the benefits of adding a biological agent, Zaltrap, to a commonly used chemotherapy drug regimen, FOLFIRI," Dr. Richard Pazdur, director of the office of hematology and oncology products in the FDA’s Center for Drug Evaluation and Research, Silver Spring, Md., said in the FDA announcement.

Click here to see a discussion of the VELOUR trial results in the journal Community Oncology.

Click here for prescribing information from the FDA.

Aflibercept, an angiogenesis inhibitor, has been approved as a second-line treatment for metastatic colorectal cancer in combination with the FOLFIRI chemotherapy regimen, the Food and Drug Administration announced on Aug. 3.

The indication is for patients whose tumors are resistant to, or have progressed after, an oxaliplatin-containing chemotherapy regimen, according to the FDA statement. The FOLFIRI regimen comprises folinic acid (leucovorin), 5-fluorouracil, and irinotecan.

Approval was based on the phase III VELOUR study of 1,226 patients with metastatic colorectal cancer whose disease progressed during treatment with oxaliplatin-based combination chemotherapy or whose tumor was surgically removed but recurred within 6 months after treatment with oxaliplatin-based combination chemotherapy. Patients continued treatment until cancer progression or unacceptable adverse effects.

The addition of aflibercept was associated with improvements in median overall survival and response rate and with a delay in tumor progression and growth: Overall survival reached a median of 13.5 months among those treated with aflibercept and FOLFIRI, vs. 12 months among those treated with placebo and FOLFIRI. Tumor size was reduced in 20% of those on the combination regimen and 11% of those receiving FOLFIRI plus placebo. In addition, median progression-free survival among patients given aflibercept and FOLIRI was 6.9 months, compared with 4.7 months in the placebo group.

Leucopenia, diarrhea, mouth ulcers, fatigue, hypertension, proteinuria, weight loss, decreased appetite, abdominal pain, and headache were among the most common side effects associated with treatment. A boxed warning covers the increased risk of severe and sometimes fatal bleeding, including gastrointestinal bleeding, GI perforations, and impaired wound healing.

Aflibercept targets the vascular endothelial growth factor (VEGF) and is also referred to as VEGF Trap. It will be marketed as Zaltrap by Sanofi-Aventis in collaboration with Regeneron Pharmaceuticals.

Another VEGF-specific angiogenesis inhibitor, bevacizumab (Avastin), was previously approved as a first- or second- line treatment of patients with metastatic colorectal cancer, in combination with intravenous 5-fluorouracil–based chemotherapy.

"This approval demonstrates the benefits of adding a biological agent, Zaltrap, to a commonly used chemotherapy drug regimen, FOLFIRI," Dr. Richard Pazdur, director of the office of hematology and oncology products in the FDA’s Center for Drug Evaluation and Research, Silver Spring, Md., said in the FDA announcement.

Click here to see a discussion of the VELOUR trial results in the journal Community Oncology.

Click here for prescribing information from the FDA.