SAN DIEGO - Researchers say that a new type of drug can help prevent advanced breast cancer from worsening, potentially providing an important new treatment option for women and a blockbuster product for Pfizer.
In a clinical trial, the drug cut in half the risk that cancer would worsen, or progress, researchers said in San Diego on Sunday. The median time before the disease progressed or the woman died was 20.2 months for those who received the drug, compared with 10.2 months for the control group.
“The magnitude of benefit we are seeing is not something commonly seen in cancer medicine studies,” said Dr. Richard Finn, a principal investigator in the study. Finn, an oncologist at the University of California, Los Angeles, called the results “quite groundbreaking.”
Breast cancer is the most common form of cancer in women, killing an estimated 40,000 a year, according to the National Cancer Institute. Hormone receptor-positive forms of the disease are typically treated by blocking hormone production in the body. When that doesn’t work, the tumor cells can begin to grow and spread, requiring chemotherapy to kill them.
Patients “don’t often do well with chemotherapy,” said Judy Garber, an oncologist at the Dana-Farber Cancer Institute in Boston and a past president of the American Association for Cancer Research. “You often feel like you’re giving more and more toxicity and less and less activity,” she said. The drugs are a promising option, she said.
Pfizer’s drug, known as palbociclib, also appeared to prolong survival, but not by a statistically significant amount. Those who received the drug lived a median of 37.5 months compared with 33.3 months for those in the control group.
The results from the Phase 2, or midstage, study were presented Sunday at the annual meeting of the American Association for Cancer Research. They are being closely watched on Wall Street, because palbociclib is considered a jewel in Pfizer’s product pipeline, with analysts predicting annual sales of billions of dollars.
Strong as the results were, it is possible they will be a bit of a letdown to some investors.
That is partly because they were not quite as good as interim results presented about halfway through the trial. At that point, the difference in median progression-free survival was 26.1 months for those taking palbociclib versus 7.5 months for the control group.
The lack of a statistically significant survival benefit could also give investors pause.
Finn said, however, that a statistically significant survival benefit should not have been expected at this point because only 61 of the 165 patients in the trial had died. Also, patients can use other drugs after leaving the trial, which can dilute any effect of palbociclib.
Palbociclib slows the runaway proliferation of cancer cells by inhibiting the activity of two related enzymes involved in cell division - cyclin-dependent kinases 4 and 6.
Breast cancer specialists not involved in the study were encouraged but somewhat cautious. “These results are strikingly positive and with a large potential impact to patients,” Dr. Jose Baselga said in a speech at the conference discussing the results.
But Baselga, who is the physician-in-chief at the Memorial Sloan-Kettering Cancer Center, said the results might have been biased because the study investigators, who determined whether tumors had progressed, knew which patients were getting palbociclib.
Dr. Eric Winer, chief of women’s cancers at the Dana-Farber Cancer Institute in Boston, said larger studies were still needed.
“This is a small Phase 2 trial - not tiny, but not the kind of study that would typically lead to a change in practice,” he said.
The study, sponsored by Pfizer, involved 165 post-menopausal women who were receiving their initial treatment for recurring or metastatic breast cancer. The cancers were estrogen receptor-positive, meaning their growth was fueled by that hormone, but negative for Her2, a different protein.
About 60 percent to 65 percent of breast cancers fit that description, according to Dr. Dennis Slamon of UCLA, another investigator in the study. Analysts at the ISI Group, an investment research firm, estimate that about 50,000 American women a year would be eligible for palbociclib.
All the women in the trial took letrozole, a drug that blocks the synthesis of estrogen. Such drugs are standard initial therapy for this type of breast cancer. About half the women also received palbociclib, which was taken orally once a day for three out of every four weeks.
The biggest side effect, experienced by about three quarters of patients, was a decreased white blood cell count. But that did not lead to infections as it usually does, according to Finn, who said that the drug was generally well tolerated.
Still, many patients had their doses reduced because of side effects, and 13 percent of patients who received palbociclib dropped out of the study because of side effects, compared with 2 percent in the control group.
A big question is whether Pfizer will be able to win approval of the drug based on this study. The Food and Drug Administration normally requires larger Phase 3 studies, but sometimes makes exceptions for drugs for cancers and other life-threatening illnesses.
If Pfizer can get early approval, the drug could probably reach the market next year. If the company must complete a Phase 3 study, which is already underway, approval might be delayed a couple of years, according to the ISI Group.
Dr. Mace Rothenberg, chief medical officer for Pfizer’s oncology division, said Thursday that the company was in discussions with the FDA and had not yet decided whether to seek approval now.
In 2008, the FDA granted accelerated approval to Genentech’s Avastin as a treatment for breast cancer based on a single trial in which the drug delayed disease progression by about 5 1/2 months.
But the women who got Avastin did not live significantly longer, and subsequent studies showed a smaller effect in delaying progression. In 2011, the FDA revoked approval of Avastin for breast cancer treatment.
While Pfizer is in the lead to bring this new class of drugs to market, Novartis has begun late-stage testing of its own CDK 4/6 inhibitor. Eli Lilly’s drug, bemaciclib, aided 61 percent of patients with metastatic, hormone-sensitive breast cancer, meaning the size of their tumors shrunk by 30 percent or didn’t increasefor 24 weeks.
Lilly’s drug was studied in a Phase 1 trial of 132 people with five types of tumors, including 36 with hormone receptor-positive breast cancer. The breast cancer patients in the trial had advanced disease and had tried about seven other treatments before Lilly’s.
Of those, tumors shrank in 25 percent of patients and stayed the same size in 55 percent. Eighteen are still taking the drug, and one has been alive almost two years after beginning therapy, according to the company. Progression-free survival, a measure of how long patients’ disease didn’t get worse, was 9.1 months.
It’s too early to know exactly how the drugs compare, though Lilly’s drug appears potent, said Mark Schoenebaum, an analyst with ISI Group in New York. One difference is that Lilly’s drug can be given continuously, Schoenebaum said, while patients using the Pfizer drug may need to break from treatment every three weeks.
The most common side effect was neutropenia, low rates of a type of white blood cell, in 11 percent of patients. Other side effects included nausea, throwing up and fatigue. About 2 percent of patients quit the drug.
“What we think we have here is an oral drug that helps prevent the growth of cancer cells, that has good single-agent activity and that you can continuously dose with low discontinuation rates,” said Richard Gaynor, senior vice president of oncology development at Lilly. The Indianapolis-based company’s drug is moving into late-phase testing, bypassing a mid-stage study.
Information for this article was contributed by Andrew Pollack of The New York Times and by Drew Armstrong of Bloomberg News.
Front Section, Pages 1 on 04/07/2014