By Randall Osborne

NEW YORK - The dominant paradigm for cancer treatment is changing, as it must, from drugs that shrink tumors to those that provide longer survival by slowing their growth, said Stephen Evans-Freke, CEO of Sugen Inc.

"It's going to require new thinking across the board," Evans-Freke told an audience at the Biotechnology Industry Organization's CEO and Investor Conference here.

Evans-Freke said conventional cytotoxic agents, proven in clinical trials to reduce tumor size, are giving way to cytostatic drugs, which "take some patients who would otherwise die and turn cancer into not a curable disease, but a manageable disease."

His remarks came during an investors session titled "Solid Tissue Tumors: New and Emerging Anti-Cancer Therapies," at which he cited as an example South San Francisco-based Sugen's small-molecule SU101, a platelet-derived growth factor inhibitor being studied in a major Phase III study for refractory glioma, or brain cancer.

The drug has been used in patients who were "very much end-stage, given life expectancy measured in weeks, not months," who were "back at work, driving cars, etc.," after two or three years of SU101 therapy. Their treatments must continue weekly, and only in some did researchers note "an objective response, 50 percent tumor shrinkage or more."

Cytostatic Agents To Hit The Mainstream, Says CEO

Evans-Freke said cytostatic agents are "the mainstream of cancer therapy going forward," and will be used "right up in the front line, in combination with existing therapies, and then potentially carrying on prophylactically in patients in remission." Oral formulations would be important, he added.

Cytostatic agents are not miracle drugs - but then, neither is chemotherapy, he said.

"It's unrealistic to ask of a cytostatic drug heroic rescue in patients that are out of all other options," he told conference attendees. "They block the growth of tumors; they don't eliminate tumors like butter in the sun. Disease-free progression is what we should be asking of these drugs in clinical development, although, at the moment, the institutional frame of reference for cancer drugs does not accept disease-free progression as a very legitimate endpoint."

Typically, Evans-Freke said, companies take cancer drugs into Phase II single-agent studies in patients who have already failed best-accepted therapy.

"By definition, you're in end-stage patients that have gone through the period when they will be most likely to benefit from a cytostatic agent," he said. Cytostatics should be used in combination with chemotherapy, "just as Herceptin [South San Francisco-based Genentech Inc.'s breast-cancer drug] ended up being in a combination study" used as the basis for its FDA filing.

"They tried to develop it as a single agent, and they couldn't do it," he said.

Like tumor shrinkage, "median time to disease progression" can be a misleading standard for cytostatics, Evans-Freke said.

"Median time to disease progression you can get by two different routes," he said. "You can give most of your patients another 60 days of disease-free survival, or you could give a small minority of your patients one- or two-year survival. I personally think the latter is worth an awful lot more than the former. But, of course, median time to disease to progression doesn't capture that."

Aside from new technologies - such as Sugen's, which focuses on signaling pathways - companies will need to come up with new designs for their trials, in order to gather data that is acceptable to regulatory authorities, "without trying to pretend that your cytostatic drug is a cytotoxic drug, because it isn't," Evans-Freke said.

"If you go to survival as your endpoint in earlier-stage patients, you have to run studies for many years," he said.

Analyst Projects $70B Cancer Therapy Market By 2030

Anthony Butler, an analyst with Lehman Brothers in New York, said that, of the 1.4 million new cases of cancer each year, about 60 percent do not represent an "addressable need."

The market is strong for cancer treatments, and will only get stronger, he said.

"While $6 billion may encompass 1998 numbers for overall market application of cancer therapy, we view it to move to just under $70 billion by 2030," Butler said.

Joseph Bertino, chairman of the Memorial Sloan-Kettering Cancer Center in New York, acknowledged the need for new approaches.

"There's a lot to do in cancer treatment," he said, noting the "tremendous fear" among patients of chemotherapy and its side effects. He said he had seen a patient recently with advanced Hodgkin's disease who "had been treating herself with herbs and unorthodox medicines for six months" before coming to Sloan-Kettering.

"Once entered into the program, she responded very nicely, but she was near death," he said.

The conference, sponsored by the Biotechnology Industry Organization and investment banking firms, including Lehman Brothers, continues through Friday.

No Comments