Chemotalk Newsletter, Vol. 54: October 1, 2012
Starting out with a question I asked Dr. Gail Roboz, Associate Professor of Medicine at Weill Cornell Medical College, The New York Presbyterian Hospital. Dr. Roboz is treating Robin Roberts ("Good Morning America"). I explained that I write a newsletter about chemotherapy, and was hoping that Dr. Roboz would give her opinion on whether or not it's safe for someone who has had stage 4 cancer that has been gone for years, to consider donating stem cells, or blood.
Here is her reply:
"Cancer patients can sometimes safely donate blood if they are cancer-free for at least 12 months, but the specific circumstances and clinical history should be reviewed at the time of donation. Stem cell collection is not performed on patients with stage 4 cancers due to potential risks to both the patient and the donor."
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Good start to October ...
NEW DRUG BEATS BACK TREATMENT-RESISTANT BREAST CANCER
By Mark Hollmer
A skin cancer drug developed by Roche's Genentech appears to beat back BREAST CANCER cells resistant to tamoxifen, a standard course of treatment, researchers from Ohio have discovered. They also figured out how those cells resistant to tamoxifen both grow and multiply.
Bhuvaneswari Ramaswamy and Sarmila Majumder of the Ohio State University Comprehensive Cancer Center made the finding, which is detailed in the journal Cancer Research. It turns out that tumors in 30% of patients with estrogen-sensitive breast cancer eventually resist tamoxifen treatment. And the research team proceeded to figure out why.
Those cells, it seems, depend on the hedgehog and PI3K/AKT signaling pathways for growth. But the researchers determined that the Roche/Genentech drug Erivedge (vismodegib) may be a solution. The drug, which gained regulatory approval last year as a treatment for advanced BASAL CELL CARCINOMA, blocks the hedgehog pathway, for one thing. And in animal tests, it stopped tamoxifen-resistant human breast tumors from growing.
On a hopeful note, the scientists think the drug could work well against tamoxifen-resistant breast cancer tumors as part of a combination targeted therapy that relies on both hedgehog and PI3K inhibitors, with no need for subsequent chemotherapy. Chemo is a typical fall-back option for tamoxifen-resistant tumors, but patients suffer from plenty of side effects.
While this option may be a long way from tests in humans, the notion that Erivedge/vismodegib could work as a treatment for tamoxifen-resistant breast cancer is tantalizing. After all, at least 30% of patients who take tamoxifen become resistant to it in 5 years, the researchers note, leaving them with chemotherapy as their only option. Those patients could certainly use another weapon for their cancer fight.
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ONCOLYTICS EXPANDS ENROLLMENT FOR CANCER DRUG LATE-STAGE TRIAL
Oncolytics Biotech Inc said it expanded enrollment in a late-stage study testing its HEAD AND NECK CANCER drug to determine its effects on two distinct patient groups.
The company, which is testing the drug, Reolysin, in combination with carboplatin and paclitaxel, doubled the number of patients enrolled in the trial to 160 following discussions with the U.S. FDA.
Oncolytics said it found patients for whom only metastatic disease was being measured were responding differently to the treatment, compared to patients who had local regional head and neck disease.
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For once, I have two pieces on MS:
NEW MS DRUG SHOWS PROMISE
A chemical that can be used as a food additive, caused serious skin infections after people sat on sofas treated with it and was approved as a psoriasis treatment in Germany 15 years ago, may prove to be a viable treatment option for people with the RELAPSING-REMITTING MULTIPLE SCLEROSIS.
Biogen Idec has announced the publication of new clinical data supporting the strong potential of BG-12.
Data from the phase III trials Define and Confirm have appeared in the New England Journal of Medicine, showing that the dimethyl fumarate therapy was able to deliver significant and clinically meaningful reductions in MS relapses and brain lesions. The therapy is intended for patients with RELAPSING-REMITTING forms of MS and is currently under review by regulatory authorities in Europe, the US, Australia, Canada and Switzerland.
Dr Katherine Dawson, senior medical director at Biogen Idec's neurology research and development unit, said: "We are working closely with regulatory authorities across the globe with the aim of making the review of dimethyl fumarate as quick as possible."
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The following story also provides a bit of insight into the Research and Development side of drug companies:
FDA OK FOR ORAL MS DRUG AUBAGIO, PRICES AT $45,000
Sanofi won a badly needed FDA approval for its oral NULTIPLE SCLEROSIS drug Aubagio (teriflunomide). And soon after the news hit a representative for Sanofi subsidiary Genzym said that the MS treatment will be priced at $45,000 a year.
"The price of Copaxone is 7% more," the rep added. "The price of Avonex is 8% more and the price of Gilenya is 28% more than the price of Aubagio." The new treatment was filed for approval by Sanofi's biologics arm, Genzyme, which will now handle the marketing.
"In a clinical trial, the relapse rate for patients using Aubagio was about 30 percent lower than the rate for those taking a placebo," commended Dr. Russell Katz, director of the Division of Neurology Products in the FDA's Center for Drug Evaluation and Research. "Multiple sclerosis can impair movement, sensation, and thinking, so it is important to have a variety of treatment options available to patients."
"We'll stack up quite well with what's out there," says David Meeker, the CEO at Genzyme. All of the drugs available carry warnings about significant side effects. And the injectables on the market present an added burden for the population that oral drugs can eliminate.
"I do predict movement," he added about the patients and physicians considering treatment regimens. "There's going to be a significantly increased willingness to try new things." And after Lemtrada makes it through the approval process on MS, where it's given a good shot at an approval, the Genzyme MS franchise will grow. "These new drugs will be highly complementary, providing meaningful choices."
In the next step, Sanofi will work to steal a march on Biogen Idec, which has won the spotlight on MS with its experimental MS drug BG-12.
R&D hasn't always been easy at Sanofi. Weeks after Genzyme filed its application for Lemtrada as a new treatment for multiple sclerosis, regulators handed the NDA back, telling the biologics arm of Sanofi that it needs to complete a rewrite before they can properly assess it. But the Aubagio sign-off follows an important approval for its cancer division. Just days ago Sanofi got its first green light for Zaltrap, a cancer drug developed with Regeneron. It's a second-line approval, in a market already dominated by Roche's Avastin and Bristol-Myers Squibb's Erbitux. But it's a step forward after a couple of oncology setbacks.
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FDA APPROVES NEW DRUG FOR METASTATIC COLORECTAL CANCER
Only three months after nabbing FDA fast-track review status for regorafenib, Bayer's top cancer prospect, the agency handed out a speedy approval as a new treatment for METASTATIC COLORECTAL CANCER. The double-quick regulatory OK completes Bayer's quick sprint through the late-stage development process, paving the way to commercialization work expected to generate peak sales of $1.25 billion a year or more.
The newly-approved drug will be marketed as Stivarga. And the FDA's release was careful to note that the agency's approval comes more than a month ahead of the agency's accelerated PDUFA date.
"Stivarga is the latest colorectal cancer treatment to demonstrate an ability to extend patients' lives and is the second drug approved for patients with colorectal cancer in the past two months," said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in FDA's Center for Drug Evaluation and Research.
The approval for regorafenib, a multi-kinase inhibitor sometimes referred to as "son of Nexavar" also marks the start of a new revenue stream for Onyx Pharmaceuticals, which gained $160 million upfront and a commitment of a hefty 20% royalty stream from Bayer after filing a lawsuit to pursue its ownership claims.
The two companies have been teamed for years on Nexavar and Onyx claimed that Bayer scientists had quietly gone to work developing a close therapeutic companion of their partnered drug. Regardless, the two companies made up after the legal scrap and are still married at the hip on the cancer front, so much so that speculation over a potential Bayer buyout has percolated for months. The buyout buzz can only grow louder with the approval news
The excitement about regorafenib's prospects has a lot to do with its effectiveness in Phase III colorectal cancer studies. Investigators reported in early January that the treatment improved the median overall survival rate of metastatic patients by 29%, with the drug arm demonstrating a 6.4 month overall survival rate while advanced patients who had already failed standard therapy survived a median average of 5 months on a placebo. Metastatic patients in the drug arm also experienced high rates of fatigue, skin reactions and diarrhea.
For Bayer, the approval marks an eagerly sought after expansion of its cancer drug franchise, which so far has relied on Nexavar, which earned $1.08 billion worldwide last year. And there's more ahead. Bayer filed applications in late August, looking for regulatory approval to market the drug for GASTROINTESTINAL TUMORS.
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Finally, I try to present as many promising pieces on cancers OTHER than breast cancer, as possible. But sometimes, a story is so important that it should be disseminated as widely as possible. This, from The New York Times, is one of them:
STUDY RESHAPING WAYS OF TREATING BREAST CANCER
FOUR TYPES IDENTIFIED
Genetic Analysis Finds Drugs Already In Use May Be Helpful
By Gina Kolata
In findings that are fundamentally reshaping the scientific understanding of BREAST CANCER, researchers have identified four genetically distinct types of the cancer. And within those types, they found hallmark genetic changes that are driving many cancers.
These discoveries, published online in the journal Nature, are expected to lead to new treatments with drugs already approved for cancers in other parts of the body and new ideas for more precise treatments aimed at genetic aberrations that now have no known treatment.
The study is the first comprehensive genetic analysis of breast cancer, which kills more than 35,000 women a year in the United States. The new paper, and several smaller recent studies, are electrifying the field.
"This is the road map for how we might cure breast cancer in the future," said Dr. Matthew Ellis of Washington University, a researcher for the study.
Researchers are patient advocates caution that it will still take years to translate the new insights into transformative new treatments. Even within the four major types of breast cancer, individual tumors appear to be driven by their own sets of genetic changes. A wide variety of drugs will most likely need to be developed to tailor medicines to individual tumors.
"There are a lot of steps that turn basic science into clinically meaningful results," said Karuna Jaggar, executive director of Breast Cancer Action, an advocacy group. "It is the 'stay tuned' story."
The study is part of a large federal project, the Cancer Genome Atlas, to build aps of genetic changes in common cancers. Reports on similar studies of LUNG and COLON cancer have been published recently. The breast cancer study was based on an analysis of tumors from 825 patients.
"There has never been a breast cancer genomics project on this scale," said the atlas's program director, Brad Ozenberger of the National Institutes of Health.
The investigators identified at least 40 genetic alterations that might be attacked by drugs. Many of them are already being developed for other types of cancer that have the same mutations. "We now have a good view of what goes wrong in breast cancer," said Joe Gray, a genetic expert at Oregon Health & Science University, who was not involved in the study. "We haven't had that before."
The study focused on the most common types of breast cancer that are thought to arise in the milk duct. It concentrated on early breast cancers that ha not yet spread to other parts of the body in order to find genetic changes that could be attacked, stopping a cancer before it metastasized.
The study's biggest surprise involved a particularly deadly breast cancer whose tumor cells resemble basal cells of the skin and sweat glands, which are in the deepest layer of the skin. These breast cells form a scaffolding for milk duct cells. This type of cancer is often called triple negative and accounts for a small percentage of breast cancer.
But researchers found that this cancer was entirely different from the other types of breast cancer and much more resembles OVARIAN cancer and a type of lung cancer.
"It's incredible," said Dr. Jaes Ingle of the Mayo Clinic, one of the study's 348 authors, of the ovarian cancer connection. "It raises the possibility that there nay be a common cause."
There are immediate therapeutic implications. The study gives a biologic reason to try some routine treatments for ovarian cancer instead of a common class of drugs used in breast cancer known as anthracyclines. Anthracyclines, Dr. Ellis said, "are the drugs most breast cancer patients dread because they are associated with heart damage and LEUKEMIA."
A new type of drug, PARP inhibitors, that seems to help squelch ovarian cancers, should also be tried in basal-like breast cancer, Dr. Ellis said.
Basal-like cancers are most prevalent in younger women, in African-Americans and in women with breast cancer genes BRCA1 and BRCA2.
Two other types of breast cancer, accounting for most cases of the disease, arise from the luminal cells that line milk ducts. These cancers have proteins on their surfaces that grab estrogen, fueling their growth. Just about everyone with estrogen-fueled cancer gets the same treatment. Some do well. Others do not.
A genetic analysis divided these cancers into two distinct types. Patients with luminal A cancer had good prognoses while those with luminal B did not, suggesting that perhaps patients with the first kind of tumor might do well with just hormonal therapy to block estrogen from spurring their cancers while those with the second kind night do better with chemotherapy in addition to hormonal therapy.
In some cases, genetic aberrations were so strongly associated with one or the other luminal sub-type that they appeared to be the actual cause of the cancer, said Dr. Charles Perou of the University of North Carolina, who is the lead author of the study. And he called that "a stunning finding."
"We are really getting at the roots of these cancers," he said.
After asal-like cancers, and luminal A and B cancers, the fourth type of breast cancer is what the researchers called HER2-enriched. Breast cancers often have extra copies of a gene, HER2, that drives their growth. A drug, Herceptin, can block the gene and has changed the prognosis for these patients from one of the worst in breast cancer to one of the best.
Yet although Herceptin is approved for every breast cancer patient whose tumor makes too much HER2, the new analysis find that not all of these tumors are alike. The HER2-enricked should respond readily to Herceptin; the other type night not.
The only way to know is to do a clinical trial, and one is already being planned. Herceptin is expensive and can occasionally damage the heart. "We absolutely only want to give it to patients who can benefit" Dr Perou said.
For now, despite the tantalizing possibilities, patients will have to wait for clinical trials to see whether drugs that block the genetic aberrations can stop the cancers. And it could be a vast undertaking to get all the drug testing done. Because there are so many different ways a breast cancer cell can go awry, there any have to be dozens of drug studies each focusing on a different genetic change.
One of Dr. Ellis's patients, Elizabeth Stark, 48, has a basal-type breast cancer. She has gone through three rounds of chemotherapy, surgery and radiation over the past four years Her disease is stable now and Dr. Stark, a biochemist at Pfizer, says she knows it will take time for the explosion of genetic data to produce new treatments that might help her.
"In 10 years it will be different," he said, adding emphatically, "I know I will be here in 10 years."
EDITOR'S NOTE: The focus of this study on patients whose breast cancers hadn't spread put me over the top of my frustration level. I found Dr. Perou's email address and sent the following message:
"I don't usually respond viscerally to studies about breast cancer, no matter how relevant they may be to my particular case. But today, as soon as I read in The New York Times that the study focused on cancers that hadn't spread, I erupted: When are "they" (whoever they are, who control these studies) going to invest in studies on breast cancer that HAS metastasized? We're the ones who will die of this, but most studies focus on learning how to prevent cancer from getting to that point.
The Komen people are only now beginning to recognize the need to focus research on metastatic breast cancer. Please. Please encourage researchers to focus on it, too. We need the results of research into mets tomorrow. Down the road won't do many of us any good, we'll be dead."
I didn't really expect a conversation, but turns out Dr. Perou is already on the case. Here's his reply:
"Rest assured we are working on metastatic cancers as well. This has been a large focus of my past, present, and future research as I agree with you 100%. CHUCK"
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Here's to a rainy fall! See you next month.
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And if you have any thoughts of how this newsletter could be improved, please email me directly, at Elaine@elainejesmer.com.