Oct. 27, 2010 -- An experimental drug is showing promise as a targeted treatment for lung cancer patients with a specific genetic abnormality.

In an early clinical trial, nearly 57% of patients with very advanced non-small-cell lung cancer (NSCLC) treated with the drug crizotinib for two months saw their tumors shrink and 33% saw their tumors stabilize.

Most had failed at least one previous round of traditional chemotherapy and some had undergone three or more previous rounds.

Only about 10% of patients with advanced lung cancer respond to approved second-line chemotherapy regimens.

The findings, which appear today in the New England Journal of Medicine, raise hopes that targeted treatments will transform cancer treatment in the future, experts say.

“These are really exciting findings, and I don’t say that about all that many studies,” American Cancer Society Deputy Chief Medical Officer Len Lichtenfeld, MD, tells WebMD. “This really has the potential to be a game changer for a select group of patients with a disease that is very difficult to treat.”

A Visual Guide to Lung Cancer
About 5% of Patients Could Benefit

Crizotinib works by blocking the anaplastic lymphoma kinase (ALK) protein, a genetic abnormality believed to promote tumor growth found in about 5% of non-small-cell lung cancer patients. The abnormality is most common in nonsmokers and younger patients.

About 10,000 of the 222,000 Americans diagnosed with non-small-cell lung cancer each year could be expected to have the genetic abnormality.

In the newly published early-phase trial, researchers identified 82 lung cancer patients with the mutation out of 1,500 screened.

When these patients were treated with the experimental drug, 47 (57%) saw their tumors shrink, and tumor growth stopped in 27 (33%) others.

Sixty-three patients continued on the drug past the trial assessment period, and some have remained on it for more than two years.

Unlike chemotherapy, there were few side effects with the targeted treatment. And many patients experienced improvement in symptoms related to their cancer after just a few weeks on the drug, researchers report.

“This therapy is allowing patients to function without pain or a constant cough,” researcher Eunice Kwak, MD, PhD, of Massachusetts General Hospital, says in a news release. “The most rewarding thing about treating patients with this drug is watching them change from being completely controlled by their cancer to resuming a very normal life.”
Larger Crizotinib Trials Under Way

Kwak says the responses were all the more remarkable because the early trial was designed to examine the drug’s safety, not its efficacy.

But despite the enthusiasm, Kwak tells WebMD that many of the patients enrolled in the early trial have developed resistance to the drug.

Acquired drug resistance has been a problem with many other targeted cancer drugs.

“Cancer cells are smart,” she says. “They tend to develop resistance to the therapies we give.”

Drug maker Pfizer, which is developing the drug, is conducting larger trials specifically designed to test its effectiveness in previously treated patients with ALK-positive tumors. A Pfizer spokesman tells WebMD that the company hopes to submit data to the FDA during the first half of next year in its bid to win approval.

It remains to be seen if the drug is as effective in patients with less advanced disease who have not been treated with chemotherapy or if combining it with chemotherapy will improve outcomes, American Cancer Society’s Lichtenfeld says.

Lung cancer researcher Roman Perez-Soler, MD, says the findings show the promise of targeted treatments for certain cancers.

Perez-Soler is chief of the Division of Medical Oncology at the Montefiore-Einstein Center for Cancer Care in the Bronx, New York.

“This is one more example of how understanding the individual characteristics of a tumor at the molecular level can help us treat the disease,” he says.

But he does not believe targeted treatments will one day be available for all cancers.

“I wish this were the case, but my feeling is that it isn’t,” he tells WebMD. “We now know that targeted therapies can work. But that doesn’t mean we will find them for all cancers.”