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FDA rejects Avastin as breast cancer therapy


4 Star


FDA rejects Avastin as breast cancer therapy

Our Review Summary

Strong points:

  • adequate evaluation of the quality of the evidence
  • relatively dispassionate review of the data
  • discussion of costs

Weaker points:

  • no quantification of harms
  • conflcting messages on benefits were probably confusing to readers
  • failed to disclose a clear conflict of interest in a source.


Why This Matters

Withdrawing a drug can be a tricky business. Like with Vioxx, some people currently taking a drug may be deriving benefit from it and tolerating it fine, but others may be harmed by it. As is clear from this article, the problem isn’t that Avastin doesn’t help anybody, it’s that doctors have no accurate way to figure out who the drug will help more than harm. And when new evidence tells us that the harms can be devastating and the benefits less, on average, than we’d hoped, its use becomes more complex to justify.

The real issue is with the future of drug development. The old idea was that one drug will help everyone, and if it doesn’t produce benefits on average, then it gets rejected. That model just doesn’t work in cancer any more. There is too much known about the heterogeneity of the disease, and we need to develop infrastructure to examine for whom it does work.


Does the story adequately discuss the costs of the intervention?


The several facets of costs are addressed, including the rationing charge. The story gets a shout out for talking about both sides of this third-rail issue with Avastin.

It would have been nice to explain Dr. Sparano’s important comment that doctors will still be able to use Avastin for breast cancer for patients who can afford it. It’s because insurance companies, including Medicare, tend not to pay for drugs when used for reasons the FDA hasn’t approved. So if Avastin does lose its indication for breast cancer, docs can still prescribe it “off-label” for that use, but patients will need to step in and pay for it all.

Does the story adequately quantify the benefits of the treatment/test/product/procedure?

Not Satisfactory

The article meets the standard here by presenting data for progression-free survival and explaining that none of the trials showed a survival benefit for Avastin compared to standard chemo. (The quantity 0 seems implied.) While it’s notoriously difficult to explain the ins and outs of cancer studies in such a short space, we nonethless criticize the article on this criterion because, although most of the messages were generally accurate, readers could’ve benefited from more clarity on one of them and a little help overall in squaring up some potentially contradictory messages. We’ll explain in 3 acts.

Act I: Story Highlights. One of these summary bullets states that “Subsequent studies showed no greater survival benefit.” In isolation this statement may be misleading. It seems they mean it to refer to progression-free survival. But that doesn’t jibe with the practical meaning of the term “survival benefit” as actually used in the body of this article: overall survival. And in fact, as we learn, all 4 studies showed no survival benefit compared to standard chemo.

Act II: Dr. Sparano’s zinger. In his opposition to the FDA decision, the source notes that one-year survival for Avastin was consistently better in all studies. How is a reader to reconcile that message with the message that survival was not better for Avastin in ANY study? What was needed was not just quantification but qualification. Perhaps it would’ve been as simple as giving us the timeframe for Dr. Woodcock’s conclusion that there was no survival benefit in all studies, or more context about Dr. Sparano’s point. Without some explanation somewhere, we think Dr. Sparano’s line should not have been quoted, since it’s essentially out of context and it somewhat throws the messages up in the air for a reader, perhaps with consequences on the balance of the story.

Act III: Mixed messages? The story gives us 2 messages that, taken together, may also seem contradictory for lay readers:

1. Later trials showed that Avastin offers a small increase in progression-free survival compared to standard chemo — but still an increase.
2. The 4 studies together shown no survival benefit.

How is a non-clinician to make sense of these messages? How can it slow tumor growth — and lengthen the time people lived without progression — but not lengthen the time people lived? These head-butting messages might’ve been reconciled by clarifying, as the FDA press release starts to, how these data show that Avastin’s effects on tumor growth were temporary enough that people taking Avastin didn’t live any longer, on average.

Does the story adequately explain/quantify the harms of the intervention?

Not Satisfactory

Harms are not quantified, and it would’ve been very helpful to know how frequently these serious side effects occurred in the trials. Were they exceptionally rare? Utterly rampant? The point of our criterion is that without quantifying the harms, readers can’t evaluate the risk/benefit trade-off for themselves.

That said, we could almost award the story credit on the spirit of this criterion because it gives the serious harms, and their implications in the FDA decision, a solid amount of time in this article. The point from the ACS medical officer that some women “have not only not benefited, they’ve been harmed,” conveys the big picture.

However, true to the definition of this criterion, we must grade this as unsatisfactory.

Does the story seem to grasp the quality of the evidence?


The story takes the time to walk us through the complex story of the preliminary study, E2100, that served as the basis for conditional approval, and the ultimate results of the larger trials, producing an implicitly higher-quality evidence base than E2100 alone. The “larger” is a big part of evaluating the evidence. It also discusses ongoing research into tumor subsets that may respond to Avastin.

Ideally it would’ve provided more detail about the 4 studies themselves, such as the numbers of subjects, designs, and lengths of follow-up. While more evidence could’ve been helpful, we think the evaluation of the larger, more relevant arc is clear, that promising preliminary results from a smaller study were not played out in several bigger studies.

Does the story commit disease-mongering?


The article avoids disease-mongering. If you want to be precise, Avastin is only approved for one type of metastatic breast cancer,  HER2-negative.

Does the story use independent sources and identify conflicts of interest?

Not Satisfactory

There was some room for improvement here. Two independent sources were used: an interview with a cancer doctor and a statement on the ACS website.  The story neglected to point out that the former, Joseph Sparano, has served as a consultant and speaker on Avastin for Genentech, as WebMD acknowledged when they interviewed him for their story.

See “Quantifying Benefits” for our request for more information about Dr. Sparano’s quote regarding 1-year survival.

On a side note, it may have balanced Dr. Sparano’s quote had the story included a little more of the ACS statement that spoke directly to the FDA decision, such as their conclusion that until we have a better way to determine who will derive the most benefit from Avastin, “giving all women with metastatic breast cancer [bevacizumab] may harm more women than it helps.”

Does the story compare the new approach with existing alternatives?


The outcomes, both potential benefits and harms, were described relative to standard chemotherapy. A bit more flesh here would’ve helped describe exactly what (and how many) other options are available.

Does the story establish the availability of the treatment/test/product/procedure?


The story is clear about Avastin’s availability and the impact of the FDA decision.

FYI: it states that the EU has decided to keep Avastin approved for breast cancer only in combination with paclitaxel. Just to be clear, in the US, it’s only approved in combination with paclitaxel , too.

Does the story appear to rely solely or largely on a news release?


It doesn’t appear to have relied solely or largely on the FDA release.

Total Score: 6 of 9 Satisfactory


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