The diagnosis was Stage 4 breast cancer. The prognosis: grave. "I got the impression that it was just like, 'Well, you're going to come here for chemo every week … kind of until you die,' " Erin Howarth said with a sardonic laugh. That was in November 2008. Howarth was just 31, and she was not ready to give up. She found a new doctor, and a new drug, Avastin. Patients take it in addition to standard chemotherapy. Within seven months Howarth's cancer was in remission. Today, Howarth is still alive, still on Avastin, still cancer-free. But now, she has a new worry: The Food and Drug Administration is poised to declare Avastin unsuitable to treat her disease.
To FDA regulators armed with studies and statistics from hundreds of patients, the debate surrounding Avastin is a question of risk vs. reward.
But for Howarth and tens of thousands of breast cancer patients like her, the controversy is decidedly more personal: What will happen if they can no longer use the drug they credit for their survival?
The FDA is scheduled to decide Avastin's fate on Sept. 17.
"It's going to be a landmark decision," said Howarth's physician, Dr. Susan Minton, an oncologist at the Moffitt Cancer Center in Tampa. "I am frightened about the impact the potential decision could have on future research."
• • •
Howarth's prognosis was bleak because the cancer had spread to her spine, skull, pelvis and right leg. Still, she balked at the pessimism of her Orlando doctors.
So Howarth went home to Chardon, Ohio, a 30-minute drive from the Cleveland Clinic Cancer Center.
That's where doctors told her about Avastin.
"I was ready for anything, hoping that anything would work," Howarth said. "I didn't care that it was new."
Now that Howarth is in drug-induced remission, she and her husband, Adam Howarth, have returned to their home in Florida.
Though they live in Orlando, Howarth receives all her treatments at Moffitt, where she found the doctors more supportive. She's decided to continue treatment indefinitely, just to be on the safe side.
"For me, I handle it pretty well," Howarth said. Side effects from her treatment come and go: fatigue, hair loss, rashes and mouth sores. "We'll see what happens, but for now, I'm definitely not going to say, 'Take me off of it.' "
• • •
The theory behind Avastin is pretty simple: starve cancer cells of what they need in order to grow, blood. In 2008, the New York Times called Avastin "a wonder drug." Doctors initially hoped that the drug would become the magic bullet that would defeat cancer for good.
Since Avastin's debut in 2004, it's become one of the most popular cancer drugs in the world. More than 700,000 patients with advanced colon, lung, kidney or brain cancer have used it.
In 2005, the company that manufactures Avastin, Genentech, sponsored a trial to test its effect on metastatic breast cancer — cancer that spreads to other parts of the body. In the trial, some women were given conventional chemotherapy alone. Others, like Howarth, were treated with a combination of chemotherapy and Avastin.
Avastin extended "progression-free survival" — the amount of time that tumors do not grow or worsen — from a median 5.8 months on chemotherapy alone to 11.3 months with the use of Avastin.
In the fight against breast cancer, results like that were a very big deal. As it stands, four out of five women with Stage 4 breast cancer die within five years.
So the FDA gave Avastin an audition, of sorts. In February 2008, it granted accelerated approval for Avastin to be used to treat metastatic breast cancer.
• • •
Howarth got her diagnosis eight months later.
She is now one of 90,000 people around the world who use Avastin to treat metastatic breast cancer.
Dr. Don Luong, a hematologist and medical oncologist at Gulfcoast Oncology Associates in Largo, said that Avastin is a preferred choice for many of his patients who qualify for the drug. The effects may be modest — it's certainly not a cure — but for women with Stage 4 breast cancer, there are few targeted therapies available, he said.
"It's been a great drug to have in our arsenal," Luong said.
Howarth, who calls herself the "poster child" for Avastin, said she couldn't agree more.
"It's worked really well for me," she said.
• • •
Even as Avastin helped keep Howarth's cancer at bay, researchers conducted more clinical trials. If the new trials were as impressive as the first, the FDA would grant the drug permanent approval.
But the results shocked the drug's supporters.
Where the first trial delayed cancer growth by 5.5 months, the new results showed a much smaller median improvement, between 0.8 and 2.9 months.
And when it came to actually prolonging life — the FDA's gold standard for cancer drug testing — Avastin failed.
In both the initial and second-round trials, difference in overall survival when patients used Avastin was practically nothing.
Side effects were another problem. Some patients experienced excessive bleeding, difficulties with wounds healing, abdominal perforation and high blood pressure.
On July 20, an FDA advisory committee voted 12–1 to recommend that the agency remove metastatic breast cancer from the list of approved uses for the drug.
That recommendation was a major blow to Genentech, whose sales of the drug reached $6 billion worldwide in 2009. Charlotte Arnold, a spokeswoman for Genentech, said the most serious side effects are exceedingly rare. More common side effects, such as high blood pressure, do not affect patients' quality of life and can usually be managed by physicians.
"Oncologists have years of experience using Avastin, and they know what to expect," Arnold said.
Howarth thinks it's ridiculous to worry about Avastin's side effects.
"People are like, 'Oh, it's such a dangerous drug,' " Howarth said. "Yeah, well, we have Stage 4 cancer. What's our choice?
• • •
One factor clouding the debate over Avastin is money. On average, a year's worth of treatment costs about $96,000. Standard chemotherapy for breast cancer patients costs about $12,000 per year.
"I think that was obviously the elephant in the room," said Dr. Gabriel Hortobagyi, one of the experts brought in to testify at the FDA advisory committee meeting in July. He is the chairman of the Department of Breast Medical Oncology at the University of Texas MD Anderson Cancer Center. "The FDA is not allowed to address that … but that was clearly in the background of everyone's mind."
The high cost of Avastin and the drug's modest clinical trial results raise a difficult question: How expensive is too expensive for treatments that offer little added benefit over existing therapy?
Hortobagyi contended that less-than-miraculous results are difficult for the FDA to justify when insurance companies pay exorbitant prices.
"I wonder if the outcome would have been the same if the drug cost $100 a month instead of $100,000 a year," Hortobagyi said.
If the FDA removes metastatic breast cancer treatment from Avastin's list of approved uses in September, doctors will still be allowed to prescribe the drug "off label" to breast cancer patients as they see fit.
But in that case, insurance companies might not provide reimbursement for the treatment. Few people would be able to pay out of pocket.
Natalie Compagni Portis, a clinical psychologist from Oakland, Calif., was a member of the FDA advisory committee who voted against Avastin. For her, she said, the disappointing clinical trial results made the question of cost moot. Who cares how much it costs if it doesn't work?
The Wall Street Journal disagrees. In its lead editorial on Aug. 18, the Journal blasted Portis and other panel members who voted against the drug, arguing that the latest trial results still showed some improvement. It labeled those who voted against the drug " … government-anointed medical patriarchs substituting their own subjective view of Avastin's risks and costs for the value that doctors and patients recognize. If Avastin is rescinded, thousands of dying women will lose more than proverbial false hope in the time they have left. They will lose a genuinely useful medicine.''
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In Hortobagyi's mind, the FDA expectations for a "successful" drug are simply too high.
"The reality is that we have very few home runs in oncology," Hortobagyi said. "There are only small, incremental improvements, but the aggregate of those small, incremental improvements add up, and those are important."
Hortobagyi said he fears that the FDA will be jumping the gun if it revokes its approval of Avastin. New drugs need time to show their stuff, he said.
"Unless we are willing to accept modest degrees of efficacy as a first signal," Hortobagyi said, "we're going to kill some perfectly good drugs that might have been helpful if we had given them enough time."
But Portis countered that viewpoints like Hortobagyi's are just too optimistic. As much as doctors and patients want to believe in this drug, the numbers simply aren't behind them.
"We're all sitting in this room talking to these expert doctors, and I'm asking myself, 'How can these very smart people not see what's here in front of them?' "
But Portis doesn't blame them. Fifteen years ago, she had breast cancer. She knows what it is to want to believe in a wonder drug.
"I want to offer patients hope, and I think everybody wants that," Portis said. "But as a patient, I don't just want be offered 'something.' I want to be offered something that could make a difference."
Martine Powers can be reached at firstname.lastname@example.org or (727) 445-4224.