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Avastin – When Science and Emotion Collide

The recent controversy leading up to and resulting from the FDA’s Oncologic Drugs Advisory Committee’s decision to withdraw its approval of Roche/Genentech’s drug Avastin for the treatment of some advanced breast cancers, seems to me, to be a perfect example of what sometimes happens when science and emotion collide.

And as so often is the case in collisions, the real victims are innocent people, in this case women with advanced HER2-negative breast cancer.

First some very basic background.

In February 2008, the FDA granted accelerated approval for the use of Avastin in treating certain advanced breast cancers. Since then it’s primarily been used in combination with paclitaxel (commonly used chemotherapy drug) for the treatment of advanced HER2-negative breast cancer.

This accelerated approval was in and of itself not without controversy. Dissenters claimed insufficient data existed to properly establish that benefits outweighed the risks.

Wasn’t this an immediate red flag?

Avastin’s use for the treatment of certain advanced breast cancers none-the-less moved forward offering hope to patients with few options remaining on the table for them.

Notably, Avastin is one of the most expensive and widely marketed cancer drugs in the world, bringing in around $6 billion annually. Roche stands to lose $1 billion of this figure if sales of Avastin for breast cancer treatment are suspended.

Avastin is the trade name for Bevacizumab and is generally given to a patient to stop or slow tumor growth by preventing formation of new blood vessels which feed the tumor. It also inhibits the function of a natural protein called vascular endothelial growth factor, or  VEGF-A, which stimulates new blood vessel growth as well as healing and repairing of the vascular system. Avastin has been used to treat other metastasized cancers such as colon and lung since 2004 when it was first approved.

This leads us to one of the greatest problems/side effects of Avastin, that being interference with normal function of blood vessels. Inhibiting  growth is good in regard to tumors, but not when it inhibits normal growth and maintenance of blood vessels throughout the body. This can lead to coronary heart disease as well as a host of other problems.

Other adverse side effects include hypertension, heightened risk of bleeding and bowel and nasal perforation to name a few.

Some such side effects have been extreme, even resulting in death.

Another issue with Avastin is the data has been inconclusive as to what exactly is benefiting the patient, the Taxol or the Avastin.

Does the Avastin boost Taxol’s effectiveness?

Who cares about any of this you might ask, especially if you are a woman living with stage IV HER2-negative breast cancer and presently taking Avastin?

What do you do when you have no other options?

This is where the recent emotional testimonies came into play. Women pleaded, some with tearful testimony, trying to make the case for keeping Avastin an option for them. Heartbreaking stories were told; stories from real women, stories about life, death and few other options.

This is where separating painful testimonial and scientific fact becomes excruciatingly difficult.

The main fact coming into play in this case was that Genentech/Roche was unable to prove patients’ overall survival (OS) or quality of life improved, not just progression-free survival (PFS), meaning tumor growth was slowed. 

Admittedly, this part bothers me. Should short-term PFS be enough?

Apparently, weighing this fact and others, together with the serious potentially deadly side effects, was enough for the FDA to withdraw its approval for Avastin.

Shouldn’t the FDA know what’s best? I sure hope so.

The manner in which all of this has been handled makes me skeptical, but ultimately, I do support this decision. I have to side with science. 

In my opinion, there is also potential danger here in parading patients around, who may or may not be in a vulnerable state of mind, in front of the media to promote a position. I think there is danger of patient exploitation here. It’s a fine line.

A couple of important points seem to be missing from the recent conversations. One being that a patient and his or her doctor can still opt to use Avastin regardless of the ruling. Also, Medicare has said it will continue covering the cost, at least for the time being, for women already on the drug.

These are important points, because no matter what, the final decision regarding continuing to use Avastin or not must be made on an individual basis by the patient and her doctor.

But, what about the women who want to continue on Avastin and are not on Medicare? Will insurance companies continue to cover this cost? Again, I’m skeptical, although with pressure being put on them to do so, they may be forced to. I hope so.

How long will sorting all this out take? 

Many patients taking Avastin don’t have the luxury of having lots of time to spare.

I don’t think this controversy is ending any time soon. The final decision will be made by FDA Commissioner Margaret Hamburg, MD, who as I understand it, can support or reject the committee’s recommendation.

In my opinion, this whole process of getting a new drug to the patient needs improvement, including better accountability, so this kind of fiasco doesn’t happen when a new drug comes down the pipeline.

We need more and better research, including more and better designed clinical trials. We need heavier emphasis on safety and the development of treatments with less debilitating side effects.

We need more and better everything for women with metastatic breast cancer.

We need to do better.

Cancer patients deserve better.

We all deserve better.

Have you taken Avastin, or do you know someone who has?

How much weight, if any, should patient testimonial have in making such decisions?

Should insurance companies continue covering the costs for women already taking Avastin and opting to continue?

 

38 thoughts on “Avastin – When Science and Emotion Collide

  1. Hi Nancy,

    Thank you for such a comprehensive and informative post. You are right, cancer patients deserve better.

    You said it so well: “… this whole process of getting a new drug to the patient needs improvement, including better accountability, so this kind of fiasco doesn’t happen when a new drug comes down the pipeline.

    We need more and better research, including more and better designed clinical trials. We need heavier emphasis on safety and the development of treatments with less debilitating side effects.”

    So well-said and very true.

    1. Beth, Thank you so much for reading and commenting. This whole Avastin thing got more than a bit ‘messy’ didn’t it? And now after the fact, so to speak, it gets even messier. Things should have been done right from the beginning, again more accountability across the board is needed.

  2. Nancy this topic is of great interest to me. I have recently done some research on availability in Australia. As a person with mets I have to ask my self to what lengths I am prepared to go to give me time?
    At this point in time, I have no answers, however, I understand the emotion involved in the decision making.
    Considering the radiation damage done to my chest wall, I am unsure about having a port inserted to simplify the delivery of Paclitaxel.
    Your Post has me thinking that it does not matter in which country I live, the choice of drugs is left in the hands of government. How much consideration is actually given to the patient’s safety?
    Love and gratitude Chez xo

    1. Chez, I so appreciate you taking time to comment as you struggle with your own personal situation. I hope if you do decide to get the port, they are beyond gentle with you. You’re right, sometimes it does seem the patient’s best interest gets lost in the shuffle doesn’t it? Good luck with all your decsions, Chez. Thinking of you.

  3. Nancy,

    Thanks for this comprehensive post. I completely agree with your points about what has been missing from the discussion. Also, I think the lesson here is that slowing tumor growth is not a valid marker for judging the success of a drug for MBC. That means we need to change trials and find out what DOES translate to success for MBC.

    Katie

    1. Katie, Thanks for commenting on this important topic. I agree, slowing tumor growth is not a valid marker for judging success of a drug. We need to do better in many areas. We have let the MBC community down for too long.

  4. For years I have commented on the very low level of success for cancer drugs. If a drug gets someone 2-3 months more of less disease burden, it is approved and applauded.
    I keep thinking that all that effort should be spent/used to produce MORE and BETTER drugs with LESS toxicity.
    I mean what the HECK is really going on?
    We can take drugs, get sick, live a little longer, take another drug, get toxicity, live a little longer. but is that the VERY BEST that BIG PHARMA can DO for US?
    I don’t think so. Let’s ASK FOR MORE!

    I am the founder of the all-volunteer http://www.annieappleseedproject.org and we offer info on natural therapies, lifestyle issues, complementary and alternative treatments. Some stuff works to enhance chemo and reduce those adverse effects. Why isn’t it WELL KNOWN?

    1. Annie, Thank you so much for commenting. I’m with you. Let’s ask for more! Let’s demand more. In the Avastin case, as I understand it, one of the biggest problems was OS vs PFS coupled with quality of life issues. I really feel the way some patients are being (or will be) jerked around is inexcusable. I also hope insurance companies will keep covering costs for those who want to stay on Avastin, but I’m skeptical here. Thanks for sharing about your project which is another valuable resource for sure.

  5. This was such an avoidable mess all the way around. Who is minding the store here? I think it’s possible to have accelerated drug approval, but everyone needs to be scrupulous about the process all the way along, and that didn’t seem to happen here.

    Once again, it points up the lack of meaningful research into effective treatments for metastatic disease. And those who have it are those who suffer.

  6. Nancy asked me to weigh in here because she knows I’m very vocal about the Avastin study.
    As a former patient of Avastin treatment I would like to put my two cents in. I am one of those who would be paraded in front of a panel, but not by the pharmaceutical gurus,nor the oncologist, but I would be a parade of one, ME…. my choice. Do I have concerns about it? Yes, but tell me what drugs never have issues. Even something as simple as an aspirin can eat a hole in my stomach. Yes, even one aspirin. It depends on the chemistry of my body and I how react to it. Did I have trouble while on Avastin? Yes. So Why would I promote it? Because in combination with my docetaxel, the first load of chemo “killed” my 2cm triple negative high grade tumor. One month it’s there, quite palpable to the touch, visible on the imaging, and next month it’s …..gone. I highly doubt that docetaxel alone worked that well.
    My troubles were some mild hypertension that I learned to control with meditation. I did seven rounds of Avastin infusion in my normal chemo loads. There was no Avastin in my last load because I did neo-adjuvant chemo, meaning my chemo came before my surgery. This means that I must be off the Avastin at least one month before undergoing surgery. Avastin affects the ability to clot. All went well with surgery and because of the success of my infusions I was able to receive a lumpectomy rather than a mastectomy. This is the goal of the oncology community, to spare the body of harsh surgery.
    I did 35 days of radiation, and then immediately began Avastin afterward, one infusion every 3 weeks(like my chemo) and was to continue for 10 rounds. I halted it after 3 loads because I was experiencing nose bleeds and I just wanted to get on with my life, get my port out and move on. I ended the study much to the disappointment of my oncology staff. I was a great success. Now my success won’t be counted in the study. It’s sad, but Avastin still should get some credit for my ability to return to my life, and for giving me the hope I received after that first round of chemo.
    I wasn’t alone. I did meet other women who had the same success as I did with Avastin. One woman had a rather large tumor in breast, and two smaller ones in chest wall, and she also has similar results.
    If I had the chance to do it all again I wouldn’t change anything. If my cancer returns(and we all know the chance of triple neg. cells returning) I will beg for Avastin. The only thing that may prevent me from getting it again? The almighty dollar. If Avastin is rejected from breast cancer treatment my insurance company will not pay for it. It cost my insurance company approx. $13,000 PER INFUSION. I sometimes wonder if the whole issue ISN’T about how effective the drug is, rather is it WORTH it. Who should decide? The FDA or me? The cost is excessive and something should be done about it, but to say that those of us who have gone before the FDA or anywhere else to speak out in favor of Avastin are being used in a supposed “vulnerable state of mind” is just wrong. The only vulnerability here is our physical health, NOT our mental health.

    1. Cheryl,
      Thank you so much for sharing about your personal experience with Avastin. Your passion comes through in your words. I do not dispute the effectiveness of Avastin for some women. If women presently taking the drug find it to be helping them, the decision to continue should be between her and her doctor. Insurance companies should not be able to opt out “after the fact,” in my opinion. That seems to border on cruelty. I do not know what the precident is here… I think the whole insurance angle is a seperate issue. I do think drugs need to come down the pipeline in a much more responsible manner. There were problems with the trials here and ultimately Roche/Genentech was unable to prove OS rates improved. There were also serious questions about quality of life/side effect issues. I do think we should demand better throughout the process. I hope Roche and the FDA did not rush the process because of the dollars involved, but like you, I do wonder… Cheryl, I wasn’t suggesting you or any of the women speaking out in this particular case are or were in a vulnerable state of mind. I was speaking more generally about the potential for exploitation that I do think exists, exploitation from both sides of the aisle. In my opinion, there is danger in that. Ultimately, we just need to do better on so many fronts. Women with mets have been livinig on the edge for too long. And 2% being spent on mets research is just plain deplorable. Thanks again for commenting, Cheryl.

  7. I totally agree with you on the mets research issue, Nancy. It seems the money and research time goes to the early stage cancers. Are researchers/donors wanting to feel better about themselves, get that pat on the back faster, easier, cheaper by choosing to research treatments for early stage vs mets? I don’t know and I sure hope not, but it makes me wonder.
    Going back to the Avastin… I wonder how many people were in my shoes and also halted the study before completion and didn’t get counted to raise the positive outcome percentage?

    1. Cheryl, Thanks for continuing to add to this discussion. It’s such an important topic. Sometimes one does have to question the motives of researchers/donors; it just seems so illogical such little attention is given to the stage of the disease that is actually deadly. You raise an interesting question here, Cheryl, about who was or was not counted in the studies. Lots of unanswered questions remain I’m afraid.

  8. This is a great synopsis of the situation, Nancy.

    There is certainly a need to fast-track certain treatments that have evidence of promise for patients who have very few other options. Yet it would be very dangerous for the FDA to weaken its standards of approval to cater to drug companies that have a lot to lose financially, or to make decisions on the basis of what insurance companies may or may not do.

    In the case of a drug that, with follow-up study, did not show adequate efficacy or had undue harm there must be a way for FDA to revoke its approval in a way that enables continued study and support for people who gained value from the treatment. Perhaps another phase of study, with more limited approval would even be appropriate so that those who may benefit from the drug can be studied further.

    In the meantime, the central problem that keeps emerging about the Avastin issue concerns the price tag and whether insurance companies will cover it. In this scenario, why aren’t advocates lobbying Pharma and insurance companies instead of the FDA?

    1. PRB, Excellent points. Your idea of continued studies and support for people who did and continue to gain value from treatment sounds totally logical. Limited approval might be a good option for the FDA to consider. I agree the point that keeps coming up, in my mind anyway, is about cost and insurance coverage. It seem unethical to me that insurance companies might be able to simply “bow out” from covering people who are benefiting. I hope some organization is on top of this issue. Thanks so much for adding to this discussion.

  9. Ditto to PRBs comment above. If we’re going to do better on developing drugs to specifically developing drugs to treat metastatic breast cancer, as opposed to drugs that are tested on mets patients, but meant for a wider market, then we’re barking up the wrong tree. We don’t need tumor shrinkage, we need to stop existing mets tumors and prevent new tumors from forming. Trouble is success at clinical trial is based on existing tumor shrinkage, so mets prevention drugs are destined to fail. So we’re left with choices like Avastin, which was such a poor choice for the women who didn’t respond and later died. We can’t lose sight of that fact. See this letter from Michael Fernandes for more information on the tumor shrinkage vs prevention issue. Eye opening! http://www.nytimes.com/2011/06/02/opinion/l02avastin.html?_r=3&ref=todayspaper

    1. Anna, You raise a very good point in your comment. The focus needs to not simply be on tumor shrinkage, but on preventing new tumor growth and metastisization. The letter from Michael Fernandes is a very good one and eye opening indeed. Thank you for sharing it.

  10. Nancy,
    Your recap of the issues surrounding Avastin is most impressive. In many respects, it’s a hard topic to get a handle on because of the emotional sides to this argument. Avastin has translated into hope, regardless of whether the science is behind it or not, and when ever our hope is taken away from us, the warrior in us is released.

    The drug companies are only to happy to use that to their advantage: They don’t want to lose a billion dollars and breast cancer women don’t want to lose hope so neither side feels like they’re being used by the other.

    I read somewhere that one of the other problems with drugs like Avastin is the drug companies may now be a little gun shy to move forward with new approaches to curing breast cancer for fear of losing a battle with the FDA. I was on the board of directors of a public company that we ultimately sold to a big pharma. We were kicked to the curb by the FDA and left with only costly recourses, so we had no choice but to bow to them. They are powerful and have nearly unlimited resources to defend their position which makes it nearly a no win situation for even the big pharmas.

    1. Brenda, Thanks for sharing your insights. Yes perhaps I should have called this piece when emotion, science and dollars collide! That probably would be more accurate. Perhaps the FDA is powerful, but I don’t want pharma having even more.

  11. Nancy, you have raised some excellent points here. Much food for thought.

    I have never taken Avastin, but I worked for Genentech, the manufacturer, for over 20 years as a patent attorney. Understandably, I don’t feel in a position to comment on the merits of the FDA decision, but I did work with someone who said her sister was alive only because of Avastin.

    I don’t think that patient testimonials should outweigh the objective scientific findings. I’m not a super emotional person (after all, I was a patent attorney, a very task- and science-oriented position), so I can’t really buy all the anecdotal evidence merely because someone voices an emotional opinion.

    But I do believe insurance companies should do the right thing and continue covering the costs for women already taking Avastin and opting to continue. Private insurance companies tend to follow Medicare in making their decisions, and I hope they do so in this situation. It’s called compassion.

    I appreciate your raising this discussion to increase our desire to decipher what clinical trials should be about.

    XOXO,
    Jan

    1. Jan, Thank you for commenting and you add a lot of insight with your experience with Genentech. I agree that insurance companies should not be allowed to just stop covering women already on Avastin and benefiting from it. Where are the advocates and lawyers taking on this cause? I hope there are some willing to tackle this part of the mess if it becomes necessary.

  12. Nancy, are you taking a stand? You seem to be agreeing with each point, which is rather confusing.

    Avastin has been effective enough so that it should remain on the market for women who will benefit, as decided by their physicians. Of course when the FDA pulls it it will not be covered by insurance. Why would an insurance company want to pay almost 100k a year for what is now considered an unproven or off-label treatment? They aren’t in business to be “nice,” and we aren’t on a playground – they are in business to be profitable.

    The truth is, metastatic women are not studied as mentioned above. Most cancer therapy is done to prevent women from getting mets. Once we do, there are only the traditional therapies out there, nobody is really looking at us.

    Some people are not understanding the statistics either. Avastin may extend survival by “only” a few months, but in reality, for any individual person, it might be extended for years. That stat is a collective stat. I recommend reading the book “Know your Chances” to understand medical statistics.

    Europe sees this quite differently, and not only are continuing to use Avastin, but have expanded its use. “The available data have convincingly shown to prolong progression-free survival of breast cancer patients without negative effect on the overall survival.”

    Any time the government decides to take something away from us “for our own good” I get concerned. The truth is, Avastin has serious side effects, as does every single chemotherapy agent out there. The truth also is, it is very effective for some women, allowing them to live many years longer than they might have. And, the final truth is that it is only used on metastatic women who have no other choice, and who are fully informed before hand. At this point, this is a decision best left to a doctor and patient. Once the government takes this choice away, women will die or be forced to shell out ungodly amounts of money.

    There are times when I’m glad I’m HER2+.

    I take exception to your saying you felt women were being “paraded” at the hearings. Nobody was forced to attend, it was voluntary, and I think women who feel passionately enough about a subject to speak in public about it should not be denigrated with terms of diminishment. They should be celebrated. I admire those women and am glad they joined the “parade.”

    1. Ann, Thank you for commenting and for voicing your opinions. First and foremost, I am appalled by the lack of attention to research for mets as you probably know if you have been following my blog. I have posted about that quite a few times. The lack of attention is deplorable, in my opinion. I don’t think that fact can be stated enough. I do think the FDA jumped the gun on approving Avastin and for sure Roche wasn’t ready with the proof to back up the efficacy of this drug in regard to OS and quality of life. I don’t really take a side here because I AM on both sides, but if forced to, I side with the science. That’s what the FDA must do as well. If we start muddying the standards for drug approval, the flood gates are opened up for drugs that may or may not be effective for OS while also possibly having herendous side effects. Ultimately, we need drugs less focused on tumor shrinkage and more focused on stopping mets from happening in the first place. No woman should be forced to stop Avastin now, after the fact, that’s wrong and I don’t think that will happen. Patient and doctor decisions are off limits in my book. Again, insurance companies will hopefully be forced to continue coverage. I think the suggestion by Pink Ribbon Blues to keep studying women presently on it, is a good one. Medicare has said it will continue coverage, so insurance companies hopefully will follow suit, especially if pressure is put on them to do so. Finally, I was not speaking specifically about these particular women being paraded around. I was speaking generally. I do think there is danger of exploitation from all sides in that. Again, as difficult as it is, science has to outweigh anecdotal evidence, but after the fact, as in this case, other considerations must be made. Thanks for the book recommendation and for your important thoughts, Ann. I really appreciate hearing from you on this emotionally charged topic. It should have been handled better. I think we all agree on that.

  13. Thank you, ButDoctorIHatePink!!!!! You’ve touched on the things I’ve been trying to say in my head, but just couldn’t get out.

  14. A couple more points…

    The FDA doesn’t take cost into consideration when making their decisions. Or personal stories. That is not their business.

    I think anyone who has a beef with this should have a beef with insurance companies and genentech. The FDA is in the business of reviewing evidence and making decisions based on science.

    Doctors can still prescribe it. If genentech is so convinced of its effectiveness, it could provide avastin for compassionate use. If they are choosing not to do that, then that’s on them, NOT on the FDA.

    Katie

  15. Oops. That was only one point.

    Ann, I don’t think it’s fair to call Nancy out for taking “sides.” She, like all of us in the bc community, wants what’s best for women with cancer. We all want a cure. I think it’s important not to lose sight of that and try to turn us against each other.

    Katie

    1. Katie, Thank you for your additional comments on this topic. I agree with your points about who the “beef” should be with and in this case I think it’s Genentech and also with the insurance companines, if they do not extend coverage. It’s a difficult situation and it’s too bad it came to this. Like my post title implies, it was a collision waiting to happen. And again, we need better emphasis on researching for drugs that do more than shrink tumors, but that actually prevent new tumor growth. The women presently on Avastin should be able to stay on if that’s their decision. They can be studied futher by Genentech. Who pays? I think the burden should fall on Genentech. Ultimately, it’s their drug, they didn’t research thoroughly enough and they are the ones who have profited and will profit further.

  16. If Avastin really is a miracle drug that is safe enough to be launched on the WIDER breast cancer population, then Genetech should be chomping at the bit to continue to study the women who are currently on the drug and should also be wiling to foot the bill. $100k/year for the number of women who are actually experiencing a response to a drug combination which includes Avastin, is small potatoes compared to the billions Genetech stands to lose with the FDA withdrawing approval. Extending financial coverage to these patients seems like good business sense to me. Keep the patients on the drug with their informed consent, study them and collect the evidence and resubmit for approval.

    1. Anna, Thank you for sharing your thoughts here. I totally agree. Genentech would benefit in the long run for sure if they did what you suggest and I think it sounds quite reasonable. Huge amounts of dollars are at stake for them. I hope someone is looking into this angle before the FDA reaches its final conclusion.

  17. Great post, Nancy. Thanks for sharing. I especially enjoyed reading all the thoughtful comments. I, too, am interested in the FDA commissioner’s decision. With how the hearing went down, I am certainly led to believe she will rule against Avastin. The FDA has surprised us before, though. Elizabeth

  18. Hello
    Has anyone experienced any severe side effects from Avastin? My mother did, so im trying to find out is there anyone else or has a family member that has experienced any severe side effects. My mother was totally independent and now she is 24/7 dependent.

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