Researchers have released a study of Genentech's experimental drug Avastin, which showed the drug modestly lengthened survival — notable in a field where even inch-by-inch improvement can be hard to document — by cutting off a tumor's blood supply.
And a study presented Sunday at the American Society of Clinical Oncology, doctors concluded Erbitux worked just as well as an earlier company-sponsored study said it did.
Genentech shares jumped Monday, as did those of ImClone Systems. It was the FDA certification process for Erbitux that got ImClone into an insider trading scandal.
Research on treatment targeting a tumor's blood supply was developed around the idea that cancer needs a growing network of blood vessels to survive — a theory championed by Harvard University's Dr. Judah Folkman. According to the theory, shutting down the process, called angiogenesis, should arrest tumors and even obliterate them.
After decades of obscurity, Folkman's theory became front-page news in 1998 with reports his angiogenesis-blocking drugs cured mice. Some predicted he was on the verge of curing human cancer, too.
"This is a landmark announcement," said Dr. William Li, head of the nonprofit Angiogenesis Foundation. "It's the first true validation in a well-designed clinical trial that cutting off a tumor's blood supply can improve cancer survival."
The treatment is an antibody aimed against vascular endothelial growth factor, or VEGF, one of the more than 20 chemicals that help tumors' blood vessels grow and survive.
The study, directed by Dr. Herbert Hurwitz of Duke University, involved 925 colon cancer patients who all received a standard chemotherapy cocktail of irinotecan, 5-fluorouracil and leucovorin. They were also randomly given either Avastin or a dummy placebo.
Those on Avastin survived an average of 20 months, compared with nearly 16 months in those getting only standard treatment. The results were a surprise, since an earlier study found no benefit of Avastin against breast cancer.
Dr. Mace Rothenberg of Vanderbilt said when he was in medical school, such patients typically survived just six months. "This improves median survival by about 30 percent," he said. "When you put it in those terms, it is very meaningful to patients."
In another major cancer study, this one involving ImClone's drug Erbitux, questions that led to the Food and Drug Administration's December 2001 rejection of the drug's approval appear to have been answered.
Erbitux is one of a new class of cancer medicines designed to work with pinpoint accuracy against the molecule-level defects that make the disease flourish. It is an antibody that jams up cancer's complex interplay of chemical growth signals.
In ImClone's initial study, Erbitux was tested on people with advanced colon cancer who had already failed to respond to irinotecan. Researchers believed Erbitux could restore some of the chemotherapy's punch.
Usually, studies are designed to test an experimental drug against the standard medicines. But in this case, doctors reasoned since the patients had already failed on irinotecan alone, any improvement with the combination could be attributed to Erbitux, so no comparison group was needed.
While the data showed nearly a quarter of patients responded to the combination, the FDA turned back ImClone's application for approval, saying Erbitux alone might have worked just as well. It also questioned whether all the patients had truly failed on chemotherapy.
The new study was conducted on 329 colon cancer patients who had clearly failed to respond to irinotecan, based on strict definitions. They were given either Erbitux alone or in combination with irinotecan.
It found 23 percent getting the combination and 11 percent taking Erbitux alone responded to treatment, meaning their tumors shrank by at least half. However, the effect was typically brief. Median survival was nearly nine months for those on the combination and seven months for patients getting only Erbitux.
Doctors who led the latest study said they felt frustrated U.S. cancer patients may have been denied a drug for years that could have helped them.
"We had desperate e-mail from patients who wanted to move to Europe to receive the drug. It was a great loss for cancer patients," said Dr. David Cunningham of Royal Marsden Hospital in England, who directed the new study and presented the findings Sunday.
Despite doubts by other cancer specialists, Dr. Robert Mayer, head of gastrointestinal cancer at Boston's Dana-Farber Cancer Institute, who was not involved in the study, contended the study demonstrates beyond doubt that Erbitux can fight cancer.
"For those who were skeptical about Erbitux, perhaps influenced by all the financial shenanigans, this clearly shows that the drug is active," he said.
ImClone's former chief executive, Dr. Samuel Waksal, pleaded guilty to securities fraud and other charges and will be sentenced June 10. He tried to sell 80,000 shares of company stock and advised his daughter to unload her holdings before news of the FDA's unfavorable decision became public. His friend, the home design celebrity Martha Stewart, is under investigation for her own sale of nearly 4,000 ImClone shares the day before the FDA announcement.
Genentech shares have surged 82 percent since the company surprised the industry and the market May 19 by reporting that Avastin, which previously had been written off as a failure in treating breast cancer dramatically extended the lives of some of the sickest colon cancer patients.