New Drug Combinations Effective on Colon Cancer

CHICAGO — Genentech Inc. reported Sunday that its experimental drug Avastin prolonged the survival of colon cancer patients by one-third over those on chemotherapy alone, providing the first successful clinical trial results of a new class of drugs designed to starve tumors of blood supply.

Two other studies released at a medical conference here provided more promising news for patients with colon cancers. Researchers at the Mayo Clinic in Minnesota reported that a cocktail of existing chemotherapy drugs was as effective in treating colon cancer as the combination used in the Avastin trial, a result that came as a surprise.

A third study showed that the controversial ImClone Systems drug Erbitux, which sparked insider trading investigations involving Martha Stewart and others, succeeded in shrinking tumors in patients with otherwise untreatable colon cancer.

Taken together, the studies mean cancer patients may soon have more effective treatment options. Colon cancer is the second-leading cause of cancer death in the United States, after lung cancer.

The most anticipated news at the annual meeting of the American Society of Clinical Oncology was the findings on Genentech’s drug. The Avastin results were in line with what the South San Francisco company led analysts to believe two weeks ago, and were strong enough for the drug to obtain Food and Drug Administration approval, doctors and analysts said.

But the unexpected results of the cocktail of existing chemotherapy drugs stole some of the thunder from Genentech’s report. In fact, some analysts predicted a sell-off in Genentech shares today by investors, who had driven the stock 65% higher on expectations that Avastin would prove a breakthrough drug in colon cancer.

Fariba Ghodsian of Castle Creek Life Sciences Partners, a hedge fund in Beverly Hills, said Wall Street’s excitement about Avastin’s near-term prospects would be damped, given that the new chemo combination for colon cancer patients was currently available and was likely to be cheaper than a biotech drug such as Avastin.

“This will definitely dilute enthusiasm,” she said. “I can see a sell-off in Genentech shares.”

Investors have added $11 billion to Genentech’s market value since May 19, when the company announced that its test of Avastin in 900 newly diagnosed colon cancer patients exceeded its expectations. But Genentech did not provide results until Sunday’s meeting of the American Society of Clinical Oncology.

The biotech company said that patients on Avastin along with conventional chemotherapy lived an average of 20.3 months, almost one-third longer than the 15.6 months for patients on chemotherapy alone. Avastin must be used in combination with chemotherapy drugs because it is not powerful enough to destroy tumors on its own. And in its study, Genentech used a standard combination of three drugs: 5-fluorouracil, leucovorin and irinotecan.

The study led by Mayo researchers, which involved 795 colon cancer patients, pitted the same chemotherapy combination used in the Genentech trial against 5-fluorouracil, leucovorin and oxaliplatin. Patients on the latter cocktail also lived 20 months. It was the first large trial in newly diagnosed colon cancer patients using oxaliplatin since the drug, from French firm Sanofi-Synthelabo, was approved last summer.

Researchers cautioned against using the two studies to compare treatment regimens.

“They appear to be similar,” said Mace L. Rothenberg of the Vanderbilt-Ingram Cancer Center in Nashville. “But until we do head-to-head trials, we won’t know the subtle differences in how they perform in patients.”

Also Sunday, researchers said ImClone’s drug Erbitux combined with irinotecan shrank tumors in 22.9% of patients. The FDA rejected the drug’s marketing application two years ago, prompting an outcry for the medication from desperate patients. The company’s stock subsequently crashed and its founder, Samuel Waksal, has pleaded guilty to insider trading.

Genentech, the nation’s first biotech company, has spent 15 years developing Avastin. The drug is the first to block formation of blood vessels that feed tumors, a promising yet difficult area that until now has seen nothing but failure.

The field attracted widespread attention in 1998, when Judah Folkman of Boston’s Children’s Hospital discovered promising drugs that eradicated tumors in mice. Researchers have been trying for 30 years to develop a drug that could cut off the blood supply to tumors in people, but have not been successful until Avastin. The intravenous medication prunes the tangled network of blood vessels that feed tumors, opening a pathway for chemotherapy drugs to reach the cancer.

Gwen Fyfe, Genentech’s vice president of oncology, said the clinical trial was designed to show that Avastin could increase a patient’s chance of survival on any given day by 33%. The drug, in fact, improves patients’ chances by 50%, she said.

“We are the first to demonstrate that if you block the growth of blood vessels, you can help cancer patients. And we improved survival, which is the hardest thing to do,” she said.

The lead investigator in the Avastin trial, Herbert Hurwitz of Duke University Medical Center, said the drug offered “a meaningful improvement in survival.”

Hurwitz also cautioned against directly comparing results of the Avastin trial with those of the oxaliplatin study. But he noted that the two trials “are benchmarking very closely.”

Investors have been looking to Avastin to drive Genentech’s future growth, with analysts forecasting that the drug would have annual sales in excess of $1 billion for colon cancer alone.

On Sunday, Ghodsian of Castle Creek Life Sciences said substantial sales were still possible if Avastin turns out to be useful in other types of cancer.

Much of the excitement over Avastin two weeks ago arose from the fact that it had succeeded in a difficult category.

Seven other highly touted drugs had failed to effectively block blood supply to tumors in clinical trials. Avastin itself did not help breast cancer patients in an earlier human test.

Although the Genentech results are strong enough for the drug to obtain FDA approval, few people offered predications Sunday on how it might fare in the marketplace against a chemotherapy combination that is likely to be less costly for patients and their insurers.

The two treatment regimes have serious side effects, though doctors said they are manageable.

Based on the data alone, “there is no rational reason to choose one or the other,” Rothenberg said.

Genentech spokesman Neil Cohen said Sunday that the company got caught in the fast-changing standard of care for colon cancer patients. When Genentech started its Avastin trial more than two years ago, oxaliplatin was not an approved drug. By the time it was approved last summer, Genentech’s clinical trial was well underway, he said.

The National Cancer Institute is testing Avastin with oxaliplatin in cancer patients, and Genentech believes that study should extend survival of patients further, Cohen said. In addition, Genentech is testing Avastin in other cancers, including kidney, where early tests have shown promise.

Alain Herrara, vice president of Sanofi’s global oncology business, also expects the addition of Avastin to the oxaliplatin combination to extend patient survival.

“I think we will have an effective treatment with Avastin,” he said. “I think we can expect to see more than 20 months.”