Monday, February 25, 2008

Of The Rack

That's right. This here post concerns hooter health, mine and everylady's.

Last week I had an ultrasound guided needle aspiration of a breast cyst. Everything is just fine, garden variety cyst, but since nothing is too personal to blog about, I wanted to share the experience with my devoted reader.
My boob was pumped full of Novacain so I didn't feel anything, and was able to watch the whole procedure on the ultrasound monitor. The doctor sucked the cyst fluid out with a syringe, and then because of some indistinguishable gray blobs on the screen, took some tissue samples, too. When I did look down at the end, gah, glad I didn't look down before because it was bloodier than I thought it would have been and also the implement the doc used to take the tissue samples looked like a caulk gun.

The coolest part was watching the needles, which appeared like a thin white line on the monitor, pierce the wall of the black blob of a cyst, and deflate it in the blink of an eye. The cysts walls stay, and though there's a chance that it will fill up again, the good news is that it will always be benign. I felt just the littlest bit sick when he showed me the teeny worms of tissue floating in a jar and the syringe full of yellowish fluid to be sent off to the lab. All that remains is a small puncture wound surrounded by a bruise and that, as they say, is that.

A day after this, the FDA approved the use of Avastin for breast cancer. Already approved for colorectal and lung cancer, Avastin brought in 2.3 billion last year in the United States alone for its creator, Genentech. So far sounds like good news for women, especially those living with breast cancer, waiting for the next drug. But there's a slight catch: the FDA approved the drug against the recommendation of its own advisory panel. In studies, Avastin had slowed the growth of tumors, but not increased survival rates. Here's the text from the committee:

Many committee members agreed that Progression Free Survival is a clinically meaningful endpoint but had issues with how best to measure this endpoint. Although the overall survival (OS) endpoint was not met, most felt that no progression is better than progression in the minds of patients. The committee also reaffirmed that if PFS is to be used then studies must also be powered for survival to ensure that benefit out way the risks. One committee member mentioned that an overall survival requirement in 1st line breast cancer is difficult to achieve due to
challenges with monitoring.

Please see the transcript for detailed discussion.

2. Summary results:
• Estimated 5.5 month improvement in median PFS claimed by Genentech
• No improvement in OS
• Increased toxicity/toxic death
• No effect on PFS or OS in 2nd and 3rd line MBC

Are the data provided sufficient to establish a favorable risk/benefit analysis for the use of bevacizumab plus paclitaxel for first-line treatment of patients with metastatic breast cancer ? (Voting Question)

Vote : Yes=4 No = 5 Abstain = 0

Not all advocacy groups are pleased with this new option. The National Breast Cancer Coalition opposes the move, saying that the FDA has "lowered the bar" by approving a drug that is not shown to be effective or safe. You can read NBCC's thoughts about Avastin here.

This is a tricky one. Even if the drug approval is ultimately pulled, as was the case with AstraZeneca’s lung cancer drug, Iressa, when trials showed it did not prolong survival, Genentech stands to makes buckets of money from the increased prescriptions that will accompany expanded FDA approval. But, it also means that many more women will have another treatment option available to them, since many insurers will not pay for "off label" prescriptions.

Of course what lies at the very root of this issue is that the American health care system does not meet the needs of most Americans, the line between science and industry is way too permeable and neither Clinton, who offers mandated insurance with penalties for those that don't comply, nor Obama, whose refusal to mandate health insurance could still see more than 15 million people uninsured, seem to offer options that are really what we need, truly universal healthcare.

Happy Monday!


Anonymous said...

Melissa - so glad to hear all is benign!!

I feel compelled to offer another POV on Avastin (disclosure: I work at Genentech!) and the FDA...see WSJ article below.

Also, as I understand it, two members of the advisory board may have changed their votes following the second study that came out earlier this month.


The Wall Street Journal (print and online) – February 21, 2008

Opinion: A Moral Test For The FDA

Some 40,000 women died from breast cancer in 2007. Almost unbelievably, the federal government may block one of the disease's more promising therapies for no other reason than the Food and Drug Administration's obsolete, even antimodern, regulations and approval models. Since the lives of terminally ill patients are in the balance, this is fundamentally a moral test – and one, true to type, that the FDA may well flunk.

At issue is the biologic medicine Avastin, which interferes with the growth and spread of tumors through the body by choking off their blood supply. Manufactured by Genentech, Avastin was approved for colorectal cancer in 2004 and lung cancer in 2006, and it's been shown effective for treating recurrent or metastatic breast cancer. But in December, the FDA's Oncologic Drugs Advisory Committee voted 5-4 against approval. The FDA is not bound by such decisions but usually follows them, and a final ruling is expected by Saturday.

A denial in this case would not only be unscientific but unethical. It's not as though the panel or the larger FDA bureaucracy don't recognize or acknowledge Avastin's real benefits. Rather, the FDA's lords of medicine may conclude that those benefits don't matter. And they don't matter, as the panel argued, because they don't fall into the categories that the FDA generally uses to evaluate the safety and efficacy of a drug.

In clinical trials, Avastin demonstrated the longest reported "progression-free survival" for patients with advanced breast cancer. That means they live longer before their disease spreads or worsens. An initial study submitted to the FDA showed that Avastin in combination with Taxol (another cancer therapy) delayed the growth of tumors by about 11 months – some five and half months longer than Taxol alone. Additionally, more than twice as many patients experienced significant tumor shrinkage.

In February, Genentech also released the preliminary findings of a more rigorous follow-up study, including the FDA's "gold standard" of randomized and placebo-controlled clinical trials. It again confirmed that Avastin improves progression-free survival, though the full results have not yet been made public.

In other words, dying patients live nearly twice as long on average before their disease gets worse, and maybe longer. It translates into an improvement in quality of life by delaying the onset of symptoms. But only in a few isolated contemporary cases has the FDA deemed progression-free survival as a relevant "end point" for approval. There's no reason besides the FDA's complacency and archaic procedures; a recent review by the agency's own Science Board concluded that "evaluation methods have remained largely unchanged over the last half-century."

Extending life is the FDA's acid test for any anticancer agent, but studies designed to prove it take years and thousands of patients to get large average effects. In the Avastin study, women lived slightly longer, a median of 26.5 months compared with 24.8 with Taxol alone. But those results weren't proved statistically significant to FDA satisfaction. Advanced therapies, however, often prove more effective among targeted populations and in some patients over others. Perhaps that's why, as the Journal's Marilyn Chase reported yesterday, even two members of the oncology panel may recant their nay votes.

At the very least, approval criteria should be broadened beyond crude mortality rates. Between the 1950s and early 1980s, when the treatments for cancer were far more limited, the FDA considered the response of tumors to treatment adequate to make judgments. Some of the most important chemotherapy drugs for cancer and autoimmune diseases gained approval during that period – cyclophosphamide, tamoxifen and others. Many are still used today, including to treat breast cancer. But it took years, sometimes decades, to learn how to use and dose them effectively once they were on the market.

No doubt thousands of lives were saved or improved by such trial and error, which is another name for medical progress. That's precisely what the FDA's bureaucratic culture, led by oncology drug chief Richard Padzur, is now obstructing. Another major culprit is political pressure from Congress, where Members know they can always get headlines by calling for a crackdown on Big Pharma or exploiting public safety anxieties. Never mind patient interest.

Patients with limited options shouldn't be denied drugs that may improve what life they have left, even if it doesn't extend life in the end. Thousands of breast-cancer sufferers, on the advice of their oncologists, are currently taking Avastin "off label," and an adverse FDA decision this week will make it far more difficult for them to do so. It would also be the latest moral indictment of everything that's wrong with the FDA.

Professional Critic said...

Thanks for sharing this!