CINDY SANDERS

Avastin® by Genentech, Inc. (NYSE: DNA), a therapeutic antibody that interferes with a tumor’s blood supply, recently received accelerated approval from the FDA for use in combination with paclitaxel chemotherapy for the first-line treatment of metastatic HER2-negative breast cancer.

The approval was granted based on positive results from the E2100 study, a Phase III clinical trial, which showed that the combination of Avastin (bevacizumab) and paclitaxel resulted in a 52 percent reduction in the risk of disease progression or death compared to those treated with paclitaxel alone. The dual delivery almost doubled a patient’s time for progression-free survival (PFS) from 5.8 months (paclitaxel alone) to 11.3 months (combination).

E2100 was a multi-center, randomized and controlled trial of 722 patients with previously untreated, locally recurrent or metastatic breast cancer. An independent, blinded review of patient scans confirmed the findings and echoed the beneficial results initially presented by the Eastern Cooperative Oncology Group at the 2005 American Society of Clinical Oncology meeting.

“In order for the accelerated approval to be converted to full approval, Genentech will have to provide the FDA with the results of two other larger studies in breast cancer: RIBBON 1 and AVADO,” said Kristina Becker, senior manager of product communications for Avastin. “We’ve communicated that we will submit those results by mid-2009.”

Dr. Denise Yardley, program director for breast cancer research at the Sarah Cannon Research Institute in Nashville, has been heavily involved in the RIBBON 1 and RIBBON 2 trials.

“From a physician standpoint,” she said, “since we don’t have a cure for metastatic breast cancer, my feeling is it’s important to control the disease as early as you can for as long as you can.”

While E2100 looked solely at Avastin in combination with paclitaxel, Yardley said that RIBBON 1 offered oncologists the option of using the biologic with a variety of standard chemotherapy drugs and combinations. Yardley added that the randomized, placebo-controlled trial was also more heavily weighted to Avastin using a 2:1 ratio “so it gave a lot more variety and breadth of combinations with Avastin.”

Of the results from E2100 and her own experience prescribing Avastin, Yardley said, “For cancer patients, it really has demonstrated slowing the tumor growth and the progression of the disease. You’re giving these women more options and longer time on their therapy with something that’s really very tolerable.”

She added that the doubling of PFS was significant. “In cancer therapies, that’s quite a substantial time to maintain a patient before someone experiences progression and growth.”

Yardley noted that survival rates get very confounded in advanced cancer cases as patients sometimes opt not to move on to second- and third-line treatments or cannot tolerate additional therapies. For that reason, she believes that the FDA looks at progression-free survival as a valid endpoint.

Becker of Genentech noted that Avastin has shown efficacy even in triple negative breast cancer, in which a patient is both HER2-negative and hormone receptor negative. Yardley said that the positive results to date for Avastin in combination with chemotherapy has led to additional studies looking at earlier interventions with the drug.

“It’s important to note,” said Becker, “Avastin is not a cure for metastatic breast cancer.” However, she continued, “By moving Avastin into earlier stages of disease, it’s our goal to help patients become cancer survivors.”

Like many new therapies, Avastin carries a high price tag. With the FDA’s accelerated approval comes the opportunity to apply for the Avastin Patient Assistance program. Becker said that only patients using Avastin for FDA-approved indications could be considered for the program, so the new approval opens the doors for advanced breast cancer patients. Healthcare providers should call the Genentech Access Solution line at 888-249-4918 for more information on eligibility requirements.

“The program caps the cost of Avastin at $55,000 per year — regardless of who is paying for it (individual or health plan) — which is comparable to the annual cost of Avastin in colon cancer,” said Becker.

Avastin has been designed to specifically inhibit the vascular endothelial growth factor (VEGF) protein, a major source of angiogenesis. Initial FDA approval was for the treatment of metastatic colorectal cancer (first- and second-line treatment) followed by approval for advanced non-squamous-, non-small-cell lung cancer. The current breast cancer indication is for advanced HER2-negative, which accounts for approximately 75 percent of metastatic breast cancers.

“From an oncologist’s standpoint, the three leading causes of cancer deaths in the U.S. — colorectal cancer, non-small-cell lung cancer and now breast cancer — have shown a treatment advantage with the addition of Avastin, the first anti-angiogenesis therapy approved by the FDA,” said Yardley.

In addition to its current indications, there are more than 300 clinical trials worldwide studying the drug’s effect on 20 different tumor types. Becker said her company announced earlier this year that they would apply to the FDA in the third quarter of 2008 for approval for Avastin as a treatment option with renal cell cancer. Additionally, Genentech has just announced it is seeking accelerated approval for use of Avastin with glioblastoma.


May 2008