ASCO: Avastin Activity Detected in Lung and Colorectal Cancers

ATLANTA, June 5 ? Adding Avastin (bevacizumab) to either standard chemotherapy or Tarceva (erlotinib) may improve progression-free survival in advanced non-small-cell-lung cancer (NSCLC), according to a phase II study reported here today.

In this six months analysis, the Avastin plus chemotherapy arm was associated with a 34% reduction in the risk of cancer progression or death, while the combination of Avastin and Tarceva reduced the risk of cancer progression or death by 28% compared with standard chemotherapy, said Alan B. Sandler, M.D., of the Vanderbilt-Ingram Cancer Center in Nashville.

The NSCLC study was one of several studies reported at the American Society of Clinical Oncology meeting that suggested, as John L. Marshall, M.D., of Georgetown University Hospital in Washington put it, "every cancer goes better with Avastin."

Dr. Marshall presented a colorectal cancer study that reported benefit for adding Avastin to a FOLFIRI (Camptosar [irnotecan HCL injection] plus 5FU/LV) regimen for treatment of metastatic colorectal cancer.

The 120-patient NSCLC trial randomized 39 patients to the Avastin-Tarceva arm, 40 patients to the Avastin chemotherapy arm, and 41 patients to chemotherapy plus placebo. Tarceva is approved for NSCLC while Avastin is not. Chemotherapy agents were either Alimta (permetrexed) or Taxotere (docetaxel).

The patients in the study had all failed at least one previous chemotherapy arm, Dr. Sandler said. As a result the positive results reported in this trial are measured in days and weeks not months or years.

Among the findings:

• Median progression-free survival was 4.8 months in the Avastin-plus-chemotherapy arm.
• Median progression-free survival was 4.4 months in the Avastin-plus-Tarceva arm.
• Median progression-free survival was 3.0 months in the chemotherapy-plus-placebo arm.

Dr. Sandler described the results as a "proof of principle" but said the principle is important: Avastin improved outcome. "And when the two targeted agents, an anti-angiogenesis agent, Avastin, and Tarceva, an inhibitor of epidermal growth factor receptor, are combined they are on a par with Avastin plus chemotherapy."

But the Avastin-Tarceva duo is less toxic and is easier to administer because Avastin is an injection rather than infusion and Tarceva is a pill.

Dr. Sandler said Genentech, which markets both drugs, is going forward with a larger randomized Phase III study in more than 600 patients comparing Tarceva with Tarceva and Avastin as second-line therapy.

The colorectal cancer trial was an open label multi-center study that randomized 430 patients with metastatic colorectal cancer to FOLFIRI, bolus Camptosar plus bolus 5FU/LV, or Camptosar plus Xeloda (capecitabine an oral 5FU).

The patients in all arms were additionally randomized to receive either Celebrex (celecoxib) or placebo because at the time the study was initiated the Cox-2 inhibitors were considering promising agents "to boost the efficacy of chemotherapy and to treat chemotherapy-related symptoms."

About halfway through the trial "Avastin became available so we added it to the FOLFIRI arm and the bolus Camptosar arm," he said.

Dr. Marshall said there are three important findings from the trial:

• Celebrex neither helps nor harms patients undergoing chemotherapy for metastatic colorectal cancer. There were no excess cardiovascular events among patients taking Celebrex.
• FOLFIRI is the superior Camptosar regimen with a median progression free survival of 8.2 months which was significantly better than other regimens (P=0.01). Median overall survival with FOLFIRI was 23.1 months.
• Avastin plus FOLFIRI is clearly superior with a one-year survival of 87%, a median progression-free survival of 9.9 months, and median overall survival not yet reached.

Asked about the surge of interest in Avastin, Dr. Marshall said "oncologists love it because you can have a patient with aggressive disease but when you give them Avastin, the tumor stops growing-right away."

But he added that while the drug is generally well tolerated it does have a number of rare, yet dangerous, toxicities-arterial thromboembolic events, intestinal perforation, and complications with wound healing.