Final Word on Avastin, and Why We Need Better Physicians

Today’s breaking breast cancer news is on Avastin. The FDA has just announced, formally, that it will rescind approval for the drug’s use in people with metastatic breast cancer. Commissioner Dr. Margaret Hamburg writes this her statement:

I know I speak on behalf of the many physicians that have been involved with this issue here at the Food and Drug Administration and elsewhere in saying that we encourage patients, and those who support them, to ask hard questions and demand explanations concerning the drugs that are recommended to treat serious illnesses.

On this much I agree with Dr. Hamburg – that patients and others, including doctors who prescribe treatments to patients with likely incurable illnesses, and all medical conditions, for that matter, should ask hard questions.

Others have already, immediately expressed that the FDA did the right thing. Because they think the FDA’s decision was rational, and it was. Likely there’ll be an editorial in the paper I usually read, celebrating the victory of reason over anecdote. The WSJ, whose words tend to align more with business interests, will likely be critical. Opponents of health care reform will, inappropriately and mistakenly, use this as an example of rationing, which it isn’t.

The fact is that many, and possibly most, medical treatments are given in the absence of studies to justify their use. So you might ask, instead, why give chemotherapy to most stage IV cancer patients. Or why give it in the adjuvant setting? Apart from some tumors, like some kinds of lymphoma and leukemia, and common breast and testicular cancers, and a few others, when carefully measured the benefit is often slim.

What I think is that Avastin is a scapegoat of sorts, a costly drug not particularly worse than many others, nor better, and that helps a small minority of women with a lethal disease for reasons their doctors can’t predict or explain.

We experiment, on insurance and Medicare dollars, with so many costly treatments. Bone marrow transplants, at a cost of hundreds of thousands of dollars per patient, for example, are given to some with little formal proof of benefit for the approved indications. But there’s a lobby for these treatments. Support comes from hospitals profiting from transplant procedures and, more subtly, from academic physicians who’ve built careers in that field and write papers about their benefits, complications and management. I might cite other complex, costly and unproved examples in oncology, surgery and other fields of medicine, but that’s not the real point for today.

What I wonder is, ironically, because the data on Avastin were collected so carefully, that its lack of effectiveness over a population of women was better-documented than has been the lack of evidence for other drugs and regimens. Besides, there’s no group of hospitals and doctors whose profit and livelihood, respectively, depends on giving Avastin to just a few people with metastatic breast cancer. There was just Genentech, an easy big-Pharma target, and a few women, pleading for continued access to a drug that’s helped to keep them alive.

(I wonder, also, had those patients who testified been men, would their words have been taken more seriously?)

Meanwhile, doctors can keep giving Avastin to patients with other forms of cancer, for which its efficacy is not so different as you might think. Like any drug, this drug’s response varies from patient to patient for every tumor type that it might be given. And the physicians can still give Avastin, as the commissioner points out in her decision, to women who can pay for it, by circumstances of their particular insurance, or good fortune of wealth. But some of these women’s families will be hurt hard by this FDA decision. Most are in the 99%.

And so maybe what we really need are better doctors, not only in oncology, who would carefully monitor patients when they give any and every medical treatment and stop it if it’s not working, and continue only if it helps, and would communicate and obtain informed consent through meaningful discourse.

If we had that, we’d save a lot of money, and get better care.

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Breast Cancer Avastin Update

This afternoon Ed Silverman of Pharmalot reports that Roche has proposed a compromise to the FDA over Avastin’s use in women with metastatic breast cancer. The drug would be approved for use only in combination with paclitaxel (Taxol), for which the data are strongest, and with special warnings.

He writes:

The deal includes revised labeling in which Avastin would be recommended only for patients displaying “aggressive disease” and who have the fewest treatment options. Roche also suggests a Risk Evaluation and Mitigation Strategy, or REMS, as well as a Medication Guide.

This sounds like a reasonable solution. As I have considered elsewhere, the FDA commissioner’s decision is pending.

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Patients’ Words, Unfiltered, Medical Journalism and Evidence

Yesterday’s post was not really about Avastin, but about medical journalism and how patients’ voices are handled by the media.

L. Husten, writing on a Forbes blog, cried that the press fawned, inappropriately, over patients’ words at the FDA hearing last week, and that led him to wonder why and if journalists should pay attention to what people with illness have to say, even if their words go against the prevailing medical wisdom.

There’s a fair amount of controversy on this. For sake of better discussion in the future, I think it best to break it up into 3 distinct but inter-related issues:

1. About health care journalism and patients’ voices:

A general problem I perceive (and part of why I started blogging) is how traditional medical journalists use patients’ stories to make a point. What some of my journalism professors tried to teach  me, and most editors I’ve dealt with clearly want, is for the reporter to find a person with an illness, as a lead,  and then tell about the relevant news, and provide some expert commentary – with at least one person speaking on each “side” of the issue, of course – and then end the story with some bit about the patient and the future.

I argue that this form of medical journalism reduces the patient to an object, used by the story-teller in order to capture the reader’s attention. So, with exceptions and always with the person’s consent, I prefer to offer my own story, from my perspective, so as not to use the patient as a vehicle or literary device.

So it appears that Husten is OK with using patients’ voices to tell a story (and sell papers/clicks?), but not with presenting their views unfiltered if they don’t mesh with the party line or a particular point an editor wants to make. This lies at the center of the journalism issue.

(As an aside, a few recent published studies have found value in analyses of patient-reported symptoms, unfiltered even by their doctors.)

2.  About Avastin:

My impression is that some beast cancer advocates, including a National Breast Cancer Coalition representative who spoke at the FDA hearing, have chosen to “take the hit” on this particular issue because they need and want to appear rational. The straightforward-seeming argument is that the data show Avastin doesn’t work and is often harmful, so it shouldn’t be FDA-approved for women with metastatic BC. From the perspective of a BC advocacy group, it may not be worth pushing for a drug that helps only around 5% of patients.

The problem is there’s no biomarker for Avastin responsiveness, because this drug doesn’t target a particular genetic marker. Rather it works by cutting the blood supply, which could vary even within a particular patient’s mets in different organs. The only way to test if Avastin works in a patient is to give the drug, with informed consent, and see how it goes. Unlike, say, a bone marrow transplant, which runs in the range of hundreds of thousands of dollars and, once done, is irreversible, you can give one dose of Avastin and stop it, or two and stop it, if it doesn’t work or it is not well-tolerated.

Based on my experience as an oncologist and patient who’s received some risky interventions, I don’t think Avastin is more toxic than many or even most cancer drugs. Rather, its side effects have been heavily pushed by the media and public health/epidemiology academics in the past two years, who perhaps wish to make a larger point about this costly drug and evidence based medicine (EBM).

3. About evidence-based medicine: I’m in favor of EBM, especially in principle. The problem is that published medical data is too-often flawed and also, that some patients are, really, outliers.

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Vicious Verbiage Targets Cancer Patients’ Voices, at Cardiobrief

A journalist who covers medical matters of the heart grabbed my attention on the Fourth of July. In The Voice of the Patient: Time To Bring Out the Muzzle?, Larry Husten at Forbes’ Cardiobrief blog, insinuates that the women who spoke at the FDA’s Avastin hearings are simpletons.

In his short strip, Husten skips the possibility that the testifying patients might understand science. He dismisses their familiarity with Avastin. He ignores their potential informational value as bona fide outliers, and jumps to this killer conclusion:

…When reporters cater to these type of people they not only foster fuzzy thinking, they encourage a mob mentality that tears down any semblance of rationality or any possibility of intelligent discourse.

Medicine, of course, is all about the patient. But that doesn’t mean that every patient is right, or deserves a public voice, or that uncritical journalists should assist them in metastasizing their views.

This is rare language in a business journal:

Phrases like “these type of people” and “mob mentality” typically reflect fear of others, based in prejudice – the opposite of reason and science, to which the author aspires. Likening patients speaking out to “metastasizing,” a term normally applied to the lethal movement of cancerous cells, reveals a disturbed view of people with illness.

The Forbes Headline, in which the author and editor, or both, contemplate using a “muzzle” to silence patients, does not approach the norm in health care journalism, or even opinion-writing.

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No Room For Emotion or Exceptions to the Rule (on Avastin)

My cousin testified before the FDA oncology advisory board on Tuesday about her experience taking Avastin. This is a tragedy, to deny the only drug that is keeping a 51 year old woman alive.

image from p.3 of today’s NYTimes business section

You have to wonder, are the advisory panel members so rational in all their behavior and choices? Are they always so razor-like in their oncology decisions?

Unlikely.

These experts have an agenda, here: It’s to be perceived as scientists, even when their knowledge is imperfect and exceptions to the rule stand right in front of their eyes. But clinical medicine calls for flexibility, and tailoring of treatment to each case, and caring about each person, including those who fall at the tail, or in this case better end, of any Kaplan-Meier survival curve.

What would Larry Kramer do about this, I’ve been thinking: He’d scream, really loud, so loud he might break his eardrums. He’d wonder why others, affected and near, aren’t doing the same. And he’d understand why this picture is on page 3 of the business section, and not on the front cover; it’s because people don’t want to look or see or know or think about it too much, because it hurts.

That is the normal heart, and this is a normal response to what’s happening to women with metastatic breast cancer.

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New Data for Avastin (Bevacizumab)

A new report was published on-line this afternoon by the Journal of Clinical Oncology (JCO). It covers a Phase III (randomized) clinical trial of Avastin (Bevacizumab) in women with metastatic BC. Over 1200 patients were included in the analysis, all with Her2 negative disease.

The design of the randomized study protocol was a bit unusual, in that the treating physicians could choose among a few, standard chemo options to give their patients – the so-called “backbone” for treatment for each cohort in the trial, along with hormonal treatment and the study drug: Avastin or a placebo. Avastin is a monoclonal antibody that binds to the vascular endothelial growth factor (VEGF). It’s manufactured by Roche and is quite costly.

What the investigators report, now, is that women who received Avastin and any of the chemo regimens did better – in terms of what’s called progression free survival – than did those who received the same chemo and placebo treatment. The difference was a matter of a few months, on average, and there were no measurable change in overall survival. What this means is that in some women with metastatic breast cancer, Avastin appears to help keep the disease in check.

The study is called RIBBON-1, which I learned this evening would be for the first study of Regimens in Bevacizumab for Breast Oncology. Sounds lame, I know, but believe me – it’s hard for oncologists to keep trials straight without acronyms. Even with the acronyms.

It happens I know some women with triple negative BC who have benefited from Avastin. These women may be outliers on the curve, but they are real and they exist and I know them personally, in what should be the middle of their lives.

Maybe we, and the FDA, shouldn’t give up so fast on Avastin.

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