A small number of patients with ovarian cancer respond to AstraZeneca's lung cancer drug Iressa, according to research published by scientists at the Fox Chase Cancer Center and Roswell Park Cancer Institute.
The findings, presented last week at the American Association for Cancer Research in Anaheim, Calif., could be significant because previously the drug had only appeared to be effective in a subset of patients with non-small cell lung cancer.
There are approximately 25,000 new cases of ovarian cancer each year, but the researchers don't know the proportion of those that are associated with a mutation in the tyrosine-kinase domain of the epidermal growth factor receptor, which is the mutation that Iressa targets, said Russell Schilder, a Fox Chase medical oncologist and the study's lead researcher.
His group found an overall frequency of tyrosine kinase-domain mutations in two of 56 ovarian adenocarcinomas examined in a preliminary retrospective study of 24 tumors, and a small prospective study of 32 tumors.
"We ran a Phase II trial through our gynecologic oncology group looking at whether or not Iressa had activity in chronic ovarian cancer," said Schilder. In 27 patients, "there was one possible responder and three other patients who had very prolonged, stable disease," he said. "At that level of clinical response, the trial closed."
In 2004, Schilder's groups read two studies, in Science and the New England Journal of Medicine, respectively, that showed that that non-small cell lung cancer patients responding to Iressa had tyrosine kinase mutations in their tumors' EGFR genes. "So we had these samples, we knew what the clinical data were, so we thought we'd look to see if it were true for ovary," Schilder said.
When Schilder's group took another look at the Phase II trial's samples, they designed a blinded trial for the small patient population. "And when it turned out there was one mutation, we said, 'Wouldn't it be funny if that turned out to be the one real responder?'" said Schilder. "We were informed later on by the GOG statistical office that, in fact, that is what happened," he added.
Iressa's clinical activity against ovarian cancer appears "relatively low, at about 4 percent," but with further targeting of mutated EGFR, its indications might be more broad than previously realized, said Schilder. "Even though the numbers are small, they do seem to track with response," he said.
Developing methods to make Iressa more useful in treating cancer "is a matter of getting the methodology geared up to handle clinical specimens right now they're all done in research laboratories," Schilder said.
The group has not yet discussed its results with AstraZeneca or other pharmaceutical companies or diagnostic companies, said Schilder.
The portion of responders from among a general patient population is too small to warrant a typical, large Phase II clinical trial, Schilder said.