FDA Approves Avastin For Breast Cancer
17 CommentsBy Ed Silverman // February 22nd, 2008 // 4:32 pm
This decision could represent a major shift in standards for assessing the effectiveness of cancer meds. In granting approval, the FDA rejected the recommendation of its advisory panel, which last December voted 5-4 against the drug, because the benefit in slowing tumor growth wasn’t believed to be worth the added risk of serious side effects, including high blood pressure and death.
At issue was whether slowing tumor growth - known as progfession-free survival - for an additional 5-1/2 months in metastatic breast cancer merits approval, even though Avastin wasn’t shown to extend life. The question, of course, resonates far beyond any one drug as the agency grapples with increasingly vocal cancer patients and their advocates, who insist any benefit is important.
For drugmakers, the approval is an important signal, because it can be expensive to conduct the lengthy trials needed to prove a drug can extend life. The approval also bolsters an industry tactic called label expansion, which is used to squeeze additional revenue out of a medication. In the case of Avastin, which is already approved to treat colon and lung cancer, Genentech may reap an additional $1.3 billion a year in revenue.
“We felt this is an effective drug for breast cancer,” Richard Pazdur, director of the agency’s Office of Oncology Drugs, tells Bloomberg News, adding that the FDA still believes survival is the “gold standard” for cancer drugs, and if further Avastin studies don’t demonstrate a benefit, the agency may require another advisory panel.
The FDA’s decision may now open the door for other cancer meds to be approved if studies find the meds can shrink tumors, although some docs worry patients may not really benefit. “If FDA sets a precedent of approving a drug based on progression free survival, people are afraid they may stop looking at survival as the most important endpoint,” Kay Dickersin, director of the Center for Clinical Trials at Johns Hopkins University, tells the Associated Press.
“The FDA has lowered the bar on the approval of breast cancer therapies. At a time when many questions are being raised about how the FDA approves drugs for market, today’s decision is a victory for drug companies, but not for patients,” Breast Cancer Action executive director Barbara Brenner says in a statement headlined ‘Patients Lose, Genentech Wins.’
Another patient advocate disagrees. “The benefits we’re looking at with Avastin matter because they give patients hope,” Margaret Kirk, president of Y-Me Breast Cancer Organization. “Without disease progression they may survive to see a discovery that can help them in the future.” But what do you think?
Was the FDA correct to approve Avastin to treat breast cancer?
- No (58%, 96 Votes)
- Yes (42%, 70 Votes)
Total Voters: 166
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“There is no cure for metastatic breast cancer so it is important to control the disease as early and for as long as possible,” Kathy Miller, associate professor of Medical Oncology, Indiana University School of Medicine and lead investigator on the E2100 trial that was reviewed by the agency, says in a statement.
MyPharmalotID
Why doesn’t the FDA just do away with advisory committees?!
It ignored the overwhelming votes on safety (17-0) and efficacy (14-3) leading to a recommendation for approval in the case of Dendreon’s Provenge for end stage prostate cancer (March 29, 2007), and then, approved Avastin after an advisory committee voted against the drug.
Talk about a waste of taxpayer money!
Gregory D. Pawelski
This mirrors the statin debacle. Drug companies didn’t have to prove that lowering cholesterol did anything positive for patients, just that it lowered cholesterol.
The Breast Cancer Action executive director says the FDA has lowered the bar on the approval of breast cancer therapies.
Well, the validation standard private insurance companies are accepting from molecular profiling tests is accuracy and not efficacy. That bar has been instantly lowered. No longer will it be essential to prove that the use of a test improves clinical outcomes, all they have to do for these molecular profiling tests is prove that the test has a useful degree of accuracy.
So we’re back to square one again. Instead of showing a drug can increase survival, all they have to do is show that it can shrink a tumor. Didn’t we just come from that neanderthal moment?
Paul
Tell patients that they can’t get a drug that lowers the chances of their cancer progressing by 50%.
And Ms. Brenner is representing a patient advocacy group?
ol cranky
I know this will sound harsh, but problem is that too many people an advocacy groups want to have their cake an eat it too. We have people/groups who think they have the right to treatment with investigational medications (not necessarily limited to those who have terminal ailments and not within the confines of a clinical trial) and yet there is still an expectation that these drugs do an will work with an exceptional safety profile. People may say they’re willing to take a risk to get a drug that is not yet proven (because they believe the drug will save their life or the life of a loved one) but they will go on the offensive when expectations aren’t met.
GK
It’s PROGRESSION FREE SURVIVAL, not PROFESSION. MBC patients, for the most part, have a terminal disease. That, coupled with multiple lines of therapy, will always confound OVERALL SURVIVAL, and make PFS the only true surrogate endpoint. This (Avastin approval for MBC), is a good thing for patients; too bad the FDA didn’t get it right the first time. How many patients missed the benefit in the meantime?
Lucy
Although Avastin slowed tumor growth for an additional 5-1/2 months in metastatic breast cancer Avastin hasn’t been shown to extend life.
In granting approval of Avastin, the FDA rejected the recommendation of its advisory panel, which last December voted against the Avastin, because the benefit in slowing tumor growth wasn’t believed to be worth the added risk of serious side effects, including high blood pressure and death.
Whereas in the case of Provenge just last May, the FDA decided counter to the overwhelming approval recommendation of its own Advisory Committee and delayed a safe and effective therapy from reaching the terminally diseased where there are no superior alternative forms of treatment.
The decision by the FDA to not make a decision on Provenge… is a decision. The absence of a decision regarding Provenge is the continuation of the status quo. Which begs the question, if the status quo is satisfactory, then why the Fast Track designation by the FDA? Is breast cancer anymore important that prostate or any other cancer?
If survival is truly the “gold standard”, then why is Avastin receiving FDA approval while safe drugs like Provenge are being delayed? This is compete bureaucratic hypocrisy!
david egilman
Patients on the drug live the exact same amount of time as those who do not take the drug. Patients who take the drug will have more bad things happen to them than patients who do not take the drug. No one will survive “long enough” to get a new miracle drug.
A patient advocate (like say a doctor) would not recommend such a drug.
Kyoto27
If Dr Richard Pazdur really wants to make a contribution to America’s war on cancer he should resign.
Instead, he is resigning America to sit through more of this ongoing farce called ‘science-based decision-making’ at the FDA.
Pazdur’s statement on Avastin—as ‘an effective drug for breast cancer’ is a slap in the face to every prostate cancer patient battling AIPC who hoped they would be able to benefit from Dendreon’s Provenge. And Dr Pazdur knows it.
And unlike Avastin, two major phase-3 trials for HRPC showed that Provenge extended survival more than twice as long as the current standard of care, Taxotere. At 36 months, more than 33% patients treated with Provenge were still alive comparing to about 15% or less on placebo. Many treated patients stayed alive and well after more than five and six years.
Other trials in the earlier disease stage, ADPC or Androgen-Dependent Prostate Cancer, also indicated that Provenge was efficacious, conforming with the general knowledge that a treatment effective in a late stage cancer would often work even better earlier when the disease has not had a chance to ravage the patient’s body.
That Pazdur/FDA went out of their way to block Provenge approval –while embracing Avastin now, is a decision made even more unfathomable now given that it went against the approval recommendation of an Advisory Committee of world-renowned scientists that the FDA, itself, convened.
While Margaret Kirk can celebrate the fact that Avastin will give breast cancer patients hope…it is my hope that organizations like Y-Me Breast Cancer realize that the FDA’s Provenge decision doomed too many desperate prostate cancer patients to die needlessly while waiting for further statistical confirmation of a treatment that has been adequately proven efficacious and known to be safe.
It’s time for the girls and the Margaret Kirk’s to join hands with prostate cancer patients and demand that the FDA start acting like a science based agency and not Richard Pazdur’s hobbyhorse.
Kerry
Well said Kyoto.
The Avastin decision was supported and received approval in part because, Richard Pazdur lobbied for it, instead of against it as he did with Provenge. The support of Pazdur for Avastin should be taken by the FDA’s Jesse Goodman to be a slap in his face. Goodman was tricked and bullied by Pazdur into not approving Provenge.
Mr. Goodman, you know CBER did not give Provenge conditional approval only because Pazdur worked so hard to sabotage it. If you did not understand that before please look at his comments before and after Prvovenge including his statements about Avastin. His comments now mirror what the prostate cancer advocacy groups have ben saying about Provenge.
Mr. Goodman now has the opportunity to use Pazdur’s own words agianst him. Goodman has the power to give approval to Provenge if he wants and he can do it now. The FDA Counsel even says so in their appellate brief now available on http://www.caretolive.com lawsuit news page.
Mr. Goodman you have the CTL Petition. Do the right thing. Do not let Pazdur intimidate you any longer.
Further review of the FDA appellate brief will demonstarte how Pazdur speaks from two sides of his mouth. In the brief Pazdurs attorneys trot out the argument that the TTP endpoint was missed even though a survival benefit was seen in Provenge. They also ignore all 17 experts opinion that Provenge is safe and try to trick the Court into thinking there are legitimate safety issues as to Provenge. There are not.
Richard Pazdur likes breasts but could do without a prostate. I don’t think he wants to face the music from the breast cancer advocactes who are admittedly much more powerful then the prostate cancer advocates.
I agree that even if drugs such Avastin are not 100% sure to work, where there are no alternative treatments and are safe, you at least give hope to those dying patients who have access. But why not give hope to AIPC patients as well.
Pazdur has already set immunotherapies back by years by waht he did to Provenge. If Provenge was being used now it would be tried in combination with other treatments and oncologists would be well on their way to determining the most efective way to use Provenge. Sitting on a shelf just means tomorrows treatments will always stay available…tomorrow.
Years from now we will look back and everyone will understand the enormity of the delay in Provnenge.
Dr. Goodman….Do the right thing and do it now!!
Steve B. RPh
How can the FDA justify this hyspocrisy? Only 1 treatment for prostate cancer and they couldn’t approve Provenge after an overwhelmingly positive advisory committe vote yet they approve a drug that gets a negative vote. Breast cancer patients have many alternatives in their treatment. There is only 1 drug for late stage PCa and the side effects might kill you before the cancer does. FDA PLEASE SAVE FACE AND APPROVE PROVENGE NOW! Call the DSMB and ask about the trials and then approve it…Please! Mens lives count too!
Philip Rudnick
Progression free survival time means no evidence of tumor growth during that specified period, NOT that you will live longer than someone who doesn’t take the drug. With Avastin, Genetech has no evidence to show that you live longer by taking the drug. Rather, the current evidence is that you don’t.
Genetech has announced its projected price for breast cancer treatment- $100,000 per year. The cost to patients will obviously depend on how long they live to take the drug.
1)Patients who cannot afford it and have no insurance to cover this price will not get it.
2) Patients who receive it will either
a) pay for it out of pocket
b) be covered to some degree by their heath insurance carrier, who will pass on the drug cost in the form of increased premiums to all its clients.
Avastin’s anti-cancer mode of action is by anti-angiogenesis, but not in a safe way - reported side effects include bleeding, kidney malfunction, reduced white cell count, gastrointestinal perforation and death. Animal studies in the scientific and medical literature (principally Medline)have documented the safe anti-angiogenic activity of the following, readily available, nutraceuticals(non-inclusive list):
Aged garlic extract(or AGE, non-odorous)from Kyolic
Alkylglycerols (in shark liver oil)
Bupleurum (herb)
EGCG from green tea
Fish oil
Flaxseed lignans (using freshly-ground flaxseeds)
Genistein (from soy protein extract)
Melatonin ~ 10-20 mg/day
Noni(available in juice form)
Pomegranate juice (available at Trader Joe’s)
Resveratrol (in grape seed/grape skin powder)
Reishi (mushroom)
Silymarin (in milk thistle herb powder)
Tocotrienols(in mixed-tocopherol,mixed-tocotrienol NATURAL vitamin E, ~100 mg/day
The eventual development of chemoresistance through genetic mutation is a virtual certainty of all direct-cancer-attacking chemo agents. Anti-angiogenesis is
a potent activity against virtually ALL types of cancer, including breast and prostate cancer. Also, because it represents an indirect attack on the cancer cell, there is rarely the development of cancer-cell resistance to this mode of action.
Someone
This was a very political decision not doubt - but it was about breast cancer. Hate to say it, but breast cancer is the most “sexy” marketable disease at the moment. If you do the tally you will find that the money being raised in the name of breast cancer research isn’t going where it is supposed to be going.
It is becoming a money making rip off.
Shame on the FDA but bigger shame to the drug company - they are playing with patients emotions in order to scam a few bucks from sick and dying patients. How pathetic…
Jack2
A) I wouldn’t connect this issue to the Provenge issue. Two wrongs don’t make a right, so why should the FDA just make the same wrong decision again?
B) Many drugs are approved on the basis of a marker, and then subsequently, the proof comes that these drugs do increase survival. Look at all the AIDS meds that get approval for lowering viral load. Subsequent data proves they can increase total lifespan. If you wait for that data many people who could benefit from the drug will not receive it and will die in the meantime.
C) Was there a trend towards increased survival in Avastin-treated patients?
someone
Jack2:
It is very discouraging to compare cancer therapies with AIDS drug. On the other hand this is the shortcoming with these targeted cancer drugs. The fact that they do not destroy the cancer causing stem cells means that eventually mutations develop that render these drugs ineffective.
Speaking of stem cells it is appalling that so much money is being wasted on drug therapies while our congress blocks important access to stem cell research. One would have to wonder if pricing could be limited to be pro rated to the actual effectiveness of the drug. Perhaps that would provide the necessary spark to fire up innovation, something that is completely missing at the moment.
The studies showed that patients did not survive any longer either with or without the drug. However, the studies for the Prostate cancer drug did show longer PFS in at least 1/3 of the patients….
Jack2
I understand there was no statistically significant difference in survival. I want to know if people lived longer in the bevacizumab group - outside of the statistical analysis. Specifically, I personally (outside of the ramifications of FDA approval) wonder if the study was underpowered to detect a difference.
Sorry to discourage you and compare AIDS and cancer(?). Cancers can develop resistance to non-targeted treatments too (eg, upregulate PgP).
Gregory D. Pawelski
No matter how reliable a drug appears to be, there’s simply little hard evidence it would make a long-term difference in a person’s prolonged survival.
Drugs are tested to show they are safe and effective before being approved by the FDA. But a clinical study is not the real world, and just because a drug leads to a statistically significant improvement doesn’t guarantee that the desired effect will follow.
There are molecular and cellular tests available to weed out those cancer patients that chemotherapy wouldn’t have any benefit, what chemotherapy works the best for those that chemotherapy would benefit, and further monitor treatment success or disease progression.
There is no proof beyond reasonable doubt for any approach to treating advanced cancer today. In life or death situations, one must make judgements based upon preponderance of available evidence as opposed to proof beyond reasonable doubt.
Bizmology » Blog Archive » Genentech wins big with Avastin approval, but will patients lose?
[...] scored a huge regulatory victory recently when the FDA approved its cancer drug Avastin as a treatment for breast cancer. The approval came as a surprise: An agency advisory committee had [...]