Taking Better Aim At Cancer

New studies point the way to more effective use of lung cancer drugs

The future of cancer treatment almost certainly lies in a new generation of targeted drugs that can knock out tumor cells without harming healthy tissue. And yet, the few such drugs developed so far have been disappointing. They work in only a small percentage of patients, who rarely live longer than they would on standard chemotherapy, and it's often unclear which patients will be helped. Three new breakthrough reports may radically improve the outlook for these drugs and revolutionize the way cancer therapies are administered.

In two of the studies, released on Apr. 29, scientists report that they have figured out how to identify which lung cancer patients will respond to Iressa, a targeted drug from AstraZeneca PLC (AZN ) that was approved last year. These two studies follow an announcement that Tarceva, an experimental drug similar to Iressa, can extend the lives of some lung cancer patients by at least one to two months. That may not seem like much, but these patients were in final stages of the disease with less than six months left. And, there have been no new, life-extending therapies for lung cancer in decades. "The events of the last couple of weeks have been nothing short of amazing," says Dr. Mark G. Kris, chief of the lung cancer service at Memorial Sloan-Kettering Cancer Center in New York. "We see people living longer, and we know why."

The why was answered by the two Iressa studies. Iressa blocks a protein called the epidermal growth factor receptor (EGFR), which tumors need to fuel their rapid spread. Although EGFR is a primary driver behind lung cancer, only about 10% of patients respond to Iressa. Research teams at Dana-Farber Cancer Institute and Massachusetts General Hospital, both in Boston, noticed that the best responders were nonsmokers, women, and Japanese. They screened the DNA of tumor tissue from patients in Iressa clinical trials and found that some cancer cells had mutations in their EGFR that made the tumor particularly aggressive -- and particularly susceptible to Iressa. Both teams reported that almost all patients with the EGFR mutation had a strong response to Iressa, while those without it gained little or no benefit. "You don't find such a clear response pattern in clinical medicine very often," says Dr. Bruce E. Johnson of Dana-Farber, a co-author of one of the studies.

"STRIKING ADVANCE". The discovery could make cancer treatment far more rational, particularly if similar genetic defects are found that correspond to other targeted therapies. A hospital could extract some of a patient's tumor cells, screen them for genetic mutations, and then determine when and if it makes sense to administer Iressa or some other drug. "This is the most striking advance in lung cancer therapy in decades," says Dr. Vincent A. Miller, a lung cancer specialist at Sloan-Kettering.

It is not yet clear how many people will be helped, or whether they will live longer. Genentech Inc. (DNA ) and OSI Pharmaceuticals Inc. (OSIP ), co-developers of Tarceva, will not release the full details of their survival trial until June. Without that data, oncologists can't properly evaluate the results.

Still, cancer specialists speculate that since Tarceva and Iressa both attack EGFR in the same way, a similar mutation may predict effectiveness for both drugs. If so, these treatments, which have minimal side effects, could be given as a first-line therapy to patients with the mutation, avoiding toxic chemotherapy. They might even prevent cancer from recurring -- at least for a while. "After surgery, patients could take a daily pill," says Dr. Daniel A. Haber, director of Mass General's cancer center. That's not a cure, but any advance is welcome.

By Catherine Arnst in New York

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