A new drug is showing remarkable promise in treating lung cancer patients who have a rare genetic mutation. The drug, crizotinib, stabilized or improved the disease in 90 percent of patients in an early stage clinical trial, according to study results released Wednesday in the New England Journal of Medicine (NEJM).
“Some of our patients will notice improvement of their symptoms within a few days or a week,” said Dr. Alice Shaw, one of the drug’s lead investigators. “These responses are dramatic.”
The drug targets a genetic mutation found in 3 to 4 percent of non-small cell lung cancer patients, typically non-smokers. The mutation, called anaplastic lymphoma kinase or ALK, triggers cancer cells to grow. Crizotinib, developed by the drug company Pfizer, inhibits the mutation and essentially shuts down new cancer cell growth.
Lung cancer
“When you turn it off they actually stop growing and many of these cells die,” Shaw said.
Crizotinib is not a cure. On average, the treatment provides patients another six to 12 months of good quality life, although some patients are still alive two years after first responding well to the drug. 57 percent of patients in the study experienced a significant reduction in the size of their tumors. The tumors shrank less in an additional 33 percent of patients who still saw their disease stabilize.
But a team of doctors led by Young Lim Choi of the University of Tokyo reported on a patient who developed two independent mutations that made the tumor resistant to crizotinib.
The appearance of resistance is not surprising, Dr. Hiroyuki Mano of the University of Tokyo said in a telephone interview. Other so-called ALK inhibitors have the same problem to some degree.
“The news is both good and bad,” said Mano. “It’s bad in that there may be some refractory population. But it’s good that we know the resistant mutations, so the next generation of ALK inhibitors will use that information to make a less refractory drug in the very near future.”
Pfizer said it planned to start submitting data for approval of the drug to the U.S. Food and Drug Administration early next year.
The experimental drug works against cells that have turned cancerous when two genes fuse to form a new gene called EML4-ALK. Although only about 3 percent to 5 percent of people with non-small-cell lung cancer fall into this category, that translates into nearly 10,000 cancer patients in the United States.
Lung cancer
Nearly all the volunteers in that study had already undergone one round of treatment with cancer drugs.
Second-round chemotherapy typically only works in about 10 percent of such cases, Bengt Hallberg and Ruth Palmer of Umea University in Sweden said in a Journal commentary.
Side-effects such as nausea and diarrhea were reported to be mild to moderate and seen in 40 percent of patients.
The medical journal also reported that the drug, sometimes designated PF-02341066, helped a 44-year-old man with a rare inflammatory myofibroblastic tumor that had the ALK mutation.
A younger patient without the mutation did not benefit from the treatment, according to a team led by Dr. James Butrynski of the Dana-Farber Cancer Institute in Boston.
Cancer cells
Existing cancer pills like AstraZeneca’s Iressa and Roche’s Tarceva are already known to be effective against cancer in patients with a mutation activating the epidermal growth factor receptor (EGFR).
Lung cancer is the most common cancer killer, with 1.61 million cases worldwide, according to the International Agency for Research on Cancer and it kills 1.2 million of them.
