Sonja[a]
In fight for life, insurer no help
Victoria Colliver, Chronicle Staff Writer
Sunday, February 12, 2006
When Neal Almgren´s glioblastoma -- the most aggressive of all brain tumors -- reappeared, he wanted his best shot at survival.
If the Mill Valley man were to rely on approved therapies, he was told his chances of suppressing the tumor were less than 10 percent. So Almgren, a 51-year-old fire-protection engineer, opted to follow the recommendation of his physician at UCSF and go an unproven route. In October, he started taking Avastin, Genentech´s colon cancer chemotherapy drug that has had some impressive results treating glioblastomas, but has been used to date in only a small number of cases.
For Almgren, the gamble has paid off. With a combination of surgery and Avastin, his tumor has shrunk to microscopic size. Although it could start growing again, the results so far are encouraging. It´s been 20 months since his condition was diagnosed. The median survival rate is 15 months.
Now Almgren faces another battle. His health insurer, Blue Shield of California, paid for the first treatment but has refused to cover the drug since.
Almgren, whose main source of income is disability insurance, has received bills totaling $196,000 and counting. The Avastin treatments, which he began receiving in October, cost about $10,000 every other week. CPT-11, a therapy given in combination with Avastin, runs $18,000 more per treatment. So far, he hasn´t paid the bills.
Blue Shield officials say there´s no hard evidence that Avastin is effective for glioblastoma patients. In fact, they fear it could be dangerous.
The insurer´s line in the sand highlights a growing conflict over whether new therapies that show promise but haven´t been formally approved should be covered, especially for patients with terminal conditions.
Almgren doesn´t have time to wait for clinical trials. And he isn´t worried about possible side effects.
"With the low number of brain tumor drugs they have, you have to go at these kinds of treatments because they´re providing the best hope we have," said Almgren, who has lost peripheral vision in the right sides of both eyes, but otherwise appears healthy. Prescribing drugs for unapproved purposes is a legal, but controversial practice known as "off-label" usage. Prescribing drugs approved by the U.S. Food and Drug Administration for unauthorized purposes is common and potentially lifesaving in some cases. But drug companies are prohibited from marketing their products for off-label use.
In some cases, off-label usage of a particular drug accumulates a solid case history and becomes standard practice. In other cases, the effectiveness and safety of a treatment is based primarily on anecdotal evidence.
The uncertain status of off-label drugs presents real dilemmas to patients and insurers. It´s a conundrum that will become increasingly common as expensive, new-generation therapies, many the products of cutting-edge biotechnology research, come on the market.
Avastin is an example of what´s known as a "targeted" therapy, a class of medications that block specific cancer mechanisms. It was approved by the FDA in February 2004 to treat colon cancer as the first drug to inhibit malignancies by choking off the blood supply to tumors.
Scientists immediately heralded the drug´s potential to treat other forms of cancer. Clinical trials of Avastin with lung and breast cancer are already in Phase III studies, the last stage before regulatory approval.
Studies involving glioblastoma patients are still in early stages. Dr. Henry Friedman, a Duke University neuro-oncologist, recently completed a Phase II study, but he has not yet published his findings in a peer-reviewed journal. Friedman said as many as two-thirds of the patients in his early-phase trial responded to the therapy.
Duke, UCSF and several other institutions are participating in a new trial sponsored by Genentech that will begin in about four months. According to Friedman, at least 100 glioblastoma patients nationwide are taking Avastin, and many are covered by private insurance. In addition to Almgren, several other patients at UCSF are receiving the treatment and are covered by various insurers including Health Net, Kaiser and the state Medi-Cal program for the poor and disabled.
Blue Shield officials say they are unaware of any clinical trials for Avastin and glioblastoma patients. Without solid evidence, such as peer-reviewed articles about the drug´s efficacy and safety, they say they can´t approve it.
Blue Shield´s decision was supported by an independent medical review requested by the Almgren family.
A panel of three general oncologists, convened by the state Department of Managed Health Care, sided with the insurer in a 2-1 vote. The Almgrens object to the decision, primarily because neuro-oncologists, not general oncologists, treat brain cancer patients.
"We´re not here to stand in the way of people to get safe and effective treatments. In this particular case, there is nothing that really supports this as a safe and effective treatment," said Dr. Eric Book, chief medical officer for Blue Shield of California, which is based in San Francisco.
The FDA has reported cranial bleeding as a potential side effect of Avastin. Book said he questions the drug´s safety, especially for use with brain tumor patients.
Book acknowledged that there´s a gray area between when physicians believe a treatment is promising and when there´s actual knowledge that it´s safe and effective. "In this particular case, we´re not even there yet," he said.
Some other experts agree.
"To say insurance companies should pay for stuff that is completely unproven is asking a lot from insurance companies," said David Magnus, director of the Stanford Center for Biomedical Ethics.
Magnus said it´s hard to tell from early-phase clinical trials whether a treatment really works. "The field is littered with things that looked incredibly promising but, when exposed to harsh light of clinical trials, failed," he said.
Insurers are quick to point to pressures they faced in the 1990s to cover an expensive therapy that combined high-dose chemotherapy with bone marrow transplantations for late-stage breast cancer patients.
Fearing lawsuits, bad press and potential legal mandates, many insurers agreed to cover the expensive treatment. But subsequent studies found the therapy was more toxic but not more effective than conventional chemotherapy.
"It is an increasingly common circumstance where we have yet-to-be-proven therapies that offer a ray of hope, sometimes without a (scientific) basis," said Dr. Sharon Levine, associate executive director of the Permanente Medical Group in Northern California, Kaiser´s physician organization.
Levine declined to comment directly on the case, but acknowledged difficulties in making such choices. "It is entirely possible everyone in this situation has behaved with complete integrity, but has come to different conclusions," she said.
Neither Levine nor other Kaiser officials would disclose the number of Kaiser members with Almgren´s diagnosis being treated with Avastin. Levine said the health maintenance organization´s policy is to cover the therapy recommended by the treating physician.
Especially devastating to patients is the lack of consistency among insurers in handling such life-and-death decisions, said Almgren´s physician, Dr. Michael Prados, professor of neurosurgery and director of the neuro-oncology clinical and laboratory research program at UCSF.
"Some companies are saying ´fine,´ and some are not. That´s very hard for patients to deal with. It´s not fair," said Prados, who confirmed that Health Net, Kaiser and Medi-Cal are paying for the treatment. He noted that some patients have been unable to receive the therapy because their insurer would not cover it and they didn´t have the money to pay for it.
Christopher Ohman, executive director of the California Association of Health Plans, acknowledged that companies handle such decisions differently. But he said the state´s medical review process is designed to help insurers and patients resolve conflicts.
Almgren was treated with surgery, approved chemotherapy and radiation when he was first diagnosed. After the tumor returned five months later, he received surgery and a clinical trial drug. For eight months, he remained tumor-free. On Sept. 6, 2005, a scan showed it was back.
"They (Almgren and his wife, Peggy) asked me what I thought was the best treatment I knew of, and I told them. The truth is this is the best known treatment I´ve seen for recurrent disease," said Prados, who called response rates to the drug "amazing." He cautioned, however, that he did not know how the Avastin therapy would perform in the long run.
He said the level of toxicity and side effects are lower for Avastin than many more conventional chemotherapy regimens.
Henry Friedman, the neuro-oncologist from Duke University, had harsh words for Blue Shield and other insurance companies that have denied reimbursement for the therapy.
"Why would anyone who cares about this patient deny him this intervention?" Friedman said. "These companies are terrific at taking somebody´s money when they´re well. They become substantially less terrific when they need to pay it out."
Blue Shield´s Book denied that the company´s decision was based on money.
For her part, Peggy Almgren says she tries to concentrate on the fact that her husband feels good and is responding to the therapy.
"I´d rather have it work and not be covered, than have it covered and not be working," she said.