Pfizer's experimental breast cancer drug stopped progression of an incurable form of the disease for more than two years in a study, a dramatic delay for those with the second deadliest cancer in women.
Patients were given the medicine, called PD 0332991, along with Novartis's Femara. The findings, reported Wednesday at the San Antonio Breast Cancer Symposium in Texas, showed no tumor progression for a median of 26.1 months, compared with 7.5 months in those who received Femara alone. Results were from the second of three stages of testing normally needed for U.S. approval.
The medicine is the first in a new class of agents that works by blocking a protein critical in the cancer cell cycle, said lead researcher Richard Finn. It's also among the most promising in New York-based Pfizer's drug development pipeline, with the potential for generating $5 billion in annual sales for breast and other tumor types, Andrew Baum, an analyst at Citigroup in London, wrote in a note to investors.
"This magnitude of benefit is probably one of the largest with any new agent in breast cancer, or perhaps any solid tumor," Finn, an associate professor of medicine at the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, said in a telephone interview. "It's dramatic to see this level of benefit with a new agent."
The findings are noteworthy because of the size of the benefit and comparative safety of the experimental treatment, said Claudine Isaacs, an oncologist and professor of medicine at Georgetown Lombardi Comprehensive Cancer Center in Washington. The study, involving 165 patients with metastatic disease, was small and must be confirmed in larger trials, she said.
The study included women with tumors fueled by the hormone estrogen, the most common type of breast cancer. All had metastatic disease, which had spread to other parts of the body and is no longer considered curable.
Breast cancer is the most common tumor in women. Almost 230,000 women in the United States will be diagnosed with it this year, and more than 39,900 will die from it, according to the American Cancer Society. Lung cancer is the deadliest form of the disease for women.
"It does make you stop and look," Isaacs said in a telephone interview. The results are "much more marked than we typically see. It's hard to ignore that," she said. "It's not something that is changing practice today, but it's definitely something to keep one's eye on."
Investors have overlooked the drug's "mega-blockbuster potential," said Baum, the Citigroup analyst. Pfizer is at least two years ahead of its closest competitors, Eli Lilly & Co. and Novartis, with similar cancer drugs in development, he said in his Nov. 29 investment note.
Pfizer rose 1.9 percent to $25.64 at 4 p.m. New York time. The shares have gained 29 percent in the past 12 months. Onyx Pharmaceuticals Inc., which licensed rights to the experimental drug to Pfizer, rose 3.4 percent to $77.05.
The results presented Wednesday stem from an interim review of the data and come on top of potent treatment, Finn said.
Forty-five percent of patients given the drug combination responded to therapy, compared with 31 percent given Femara alone. When the researchers included women who had stable disease for six months or more, 70 percent given both drugs benefited, compared with 44 percent of those given Femara.
Pfizer is moving the compound into the final stage of testing needed for approval as quickly as possible, with an international trial in the same type of cancer slated to begin next year, said Mace Rothenberg, senior vice president of clinical development in the company's oncology unit. Additional research is examining other types of tumors, he said.
The company is also talking to regulators to determine what kind of information will be needed to win marketing approval of the medicine, he said in a telephone interview. While the Food and Drug Administration typically requires two studies confirming the benefits of an investigational agent, it has leeway to expedite the process for promising drugs.
About one in three patients needed to have their dose of the experimental drug lowered during the study. Side effects included low levels of infection-fighting white blood cells, anemia and fatigue, though there weren't any serious cases of fever tied to the low white blood cells.
The first 66 patients were post-menopausal women with estrogen-receptor positive cancer. The second 99 patients also had tumors that were fueled by estrogen, though they had genetic alterations the researchers hoped could further identify people who would benefit from the therapy.
About half the women were initially diagnosed with advanced disease and hadn't gotten previous drug treatment. The other half had previously received chemotherapy or treatment after surgery to remove the tumor, Finn said. Laboratory work conducted before the study began suggested the Pfizer medicine was particularly potent against estrogen-receptor positive cancers.
There were no differences in response among women with the biomarkers and those who didn't have them, Finn said. Both sets of patients had a significant benefit.
"The drug obviously hits a critical pathway in estrogen- receptor positive breast cancer," he said. "If we took triple negative breast cancer, we wouldn't expect this result."
Pfizer is reaching out to cancer experts to help devise the most efficient studies to answer questions about when and how the drug should be given, and what other medicines should be given with it to maximize the benefit, Rothenberg said.
"It's an irony of having a drug moving forward as quickly as we can," Rothenberg said. "There will be gaps in our knowledge of how to give it and when. We're trying to move forward with a thoughtful, methodical approach."
The study targeted women who were newly diagnosed with metastatic, or spreading, breast cancer. There are several other effective treatments available even after the experimental compound stops working, Finn said.
"The magnitude of this benefit I don't think should be underestimated," Finn said. "These are patients who have incurable breast cancer. A lot of drugs in oncology have been approved or are getting a lot of traction because of improvements that last weeks to a few months. We have gone from 7 months to 26 months. That's groundbreaking."