Experimental Drug Shows Promise for Drug-Resistant Lung Cancer
WEDNESDAY, March 26, 2014 -- A new drug may help lung cancer patients when they become resistant to the first-line medication crizotinib, researchers find.
Although crizotinib (brand name Xalkori) causes regression of a specific type of lung cancer, patients become resistant to it within about a year. But the new drug, ceritinib (FDA approved under brand name Zykadia on April 29, 2014), seems effective against this type of lung cancer -- called advanced ALK-positive non-small cell lung cancer -- according to the results of early trials.
"Ceritinib is even effective after the first-generation drug crizotinib has stopped working," said lead researcher Dr. Alice Shaw, an associate professor of medicine at Harvard Medical School in Boston.
Preliminary results from this study led the U.S. Food and Drug Administration to give ceritinib a "breakthrough therapy" designation and led the drug's manufacturer to recommend accelerated approval, she said. "It is possible that ceritinib may become another standard therapy for patients with ALK-positive lung cancer," she said.
Patients with this form of cancer carry a genetic change in the ALK gene and account for 3 percent to 7 percent of non-small-cell lung cancer cases, Shaw said.
"Given the large number of cases each year, this small percentage actually translates into a large number of ALK patients -- roughly 40,000 new cases each year worldwide," Shaw explained.
In this study, ceritinib was effective in patients already treated with crizotinib and in untreated patients. "In particular, in patients who had already failed on previous crizotinib, ceritinib was able to re-induce remission in the majority of patients," Shaw said.
After seven months of treatment, however, most patients developed resistance to ceritinib.
The report, published March 27 in the New England Journal of Medicine, was partially funded by Novartis Pharmaceuticals, the maker of ceritinib.
Dr. Roman Thomas, author of an accompanying journal editorial, called the findings "good news for patients with ALK-rearranged lung cancer, who may benefit from another line of treatment with a new drug."
It is likely that patients will live longer if treated with both drugs, added Thomas, who works in the department of translational genomics at the University of Cologne in Germany.
"Ceritinib can overcome resistance to crizotinib, but no drug has so far been developed that can overcome resistance to ceritinib. The most likely sequence of therapy is crizotinib first, followed by ceritinib," Thomas said.
For the study, researchers gave 59 patients daily doses of ceritinib ranging from 50 milligrams to 750 milligrams to find the highest dose they could tolerate.
"The side effects of ceritinib include nausea, vomiting, diarrhea, liver function-test abnormalities and abdominal pain," Shaw said. "These side effects are usually mild and manageable, and they are reversible, but we do often need to reduce the dose of ceritinib to minimize side effects."
In a second phase of the study, another 71 patients were given ceritinib for as long as the drug was effective with dose adjustments to reduce side effects.
About 60 percent of patients saw tumors reduced in size and number.
Those who continued to respond to ceritinib have stayed on it, some for as long as two years, the researchers said.
Because ceritinib is not yet approved by the FDA, pricing hasn't been established, Shaw said. However, as with most new drugs, it is likely to be expensive.
Crizotinib, approved in 2011, costs around $12,000 for 30 pills or about $144,000 a year.
For more information on lung cancer, visit the U.S. National Cancer Institute.
Posted: March 2014
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