FDA approves second-line bevacizumab plus chemo for metastatic colorectal cancer

Bevacizumab plus FOLFOX4 resulted in a 25% reduction in the risk of death, a 33% improvement in overall survival, compared with FOLFOX4 alone.

Issue: July 1, 2006

The FDA has approved bevacizumab (Avastin, Genentech) with IV 5-fluorouracil-based chemotherapy for second-line metastatic colorectal cancer. Bevacizumab is also approved as a first-line treatment of metastatic colorectal cancer with IV 5-fluorouracil-based chemotherapy. Bevacizumab is a therapeutic antibody designed to inhibit vascular endothelial growth factor.

“Avastin is the only biologic therapy with a demonstrated survival benefit in colorectal cancer, and this new indication offers colorectal cancer patients who have received a previous treatment regimen a new option to help fight their disease,” said Hal Barron, MD, senior vice president of development and chief medical officer at Genentech, in a prepared statement. “Avastin used in combination with chemotherapy has become an important component of care for patients with metastatic colorectal cancer.

Approved [drawing] “Researchers are examining bevacizumab in both the adjuvant and metastatic settings and have launched phase-3 trials in kidney, breast, pancreatic, non–small-cell lung, prostate and ovarian cancers in the hope that we may be able to help patients with other cancers as well,” he said

The approval is based on results of a randomized, controlled, multicenter phase-3 trial (E3200) of 829 patients with advanced or metastatic colorectal cancer who had received previous treatment with irinotec- an and 5-fluorouracil (5-FU) as initial therapy for metastatic disease or as adjuvant therapy.

The study showed that patients who received bevacizumab plus the 5-FU-based chemotherapy regimen FOLFOX4 (oxaliplatin, Eloxatin, Sanofi Aventis, 5-FU and leucovorin) had a 25% reduction in the risk of death (HR=0.75), a 33% improvement in overall survival, compared with patients who received FOLFOX4 alone. Median survival for patients receiving bevacizumab plus FOLFOX4 was 13 months, compared with 10.8 months for those receiving FOLFOX4 alone.

“Colorectal cancer is the second leading cause of cancer death in the United States, so we are encouraged by new treatments and options that are leading to increased survival for patients,” said Amy E. Kelly, co-founder and executive director of the Colon Cancer Alliance. “We believe Avastin is an important advance that offers hope for prolonging survival for patients, including those who have already been through first-line treatment.”

In the E3200 study, the most common acute adverse events, which occurred at a higher incidence of at least 2% in the bevacizumab plus FOLFOX4 arm, compared with the FOL- FOX4 alone arm, were diarrhea, nausea, vomiting, dehydration, ileus, sensory neuropathy, other neurologic events, fatigue, abdominal pain, headache, hypertension and hemorrhage.

The trial was sponsored by NCI, and was conducted by a network of researchers led by the Eastern Cooperative Oncology Group (ECOG). Genentech supported the trial.