Pharma Strategy Blog

Finally, we have a result from the public hearing in Washington DC on whether Avastin is a safe and effective drug in first line treatment of metastatic breast cancer after the Oncology Drugs Advisory Committee (ODAC) voted 6-0 against on all three questions (was Avastin effective, safe and should the indication continue to be upheld).

An overwhelming victory for CDER’s case rather than Genentech/Roche’s.

For those of you wondering whether there was any wriggle room for manoeuvre, take a look at the data for yourselves from the original ODAC meeting last year when the FDA reviewed it.  I put together the response rates and survival curves from the RIBBON1 and AVADO trials at the time, based on the publicly available data on the FDA site for all to see.

Essentially, the 5.5 month survival advantage seen in the original trial (E2100) that garnered approval was not confirmed, with the PFS in the follow up trials virtually disappearing.  The systemic side effects of the drug were however, repeated.  It should be noted that none of the three trials showed any improvement in overall survival, so patients sadly did not in fact, live longer on Avastin than with chemotherapy alone.

Like many people, I ardently wish the results were more positive and significantly so – we would at least have better options for women with breast cancer.  Sadly, they are not and the data wasn’t even close.  Had the two additional trials showed a 5 month benefit per the original E2100 trial that was used to support the initial approval, then I don’t think we would have seen the FDA move to suggest withdrawal of Avastin in December.  In fact, it would have been a clear slam dunk the other way.

It’s easy to say that some women benefited (they clearly did) and that some were harmed by the toxicities or did worse (that is equally clear), but as Francis Collins of the NIH recently said, “anecdote is not the plural of data.”

In the absence of any biomarker to help predict response or suggest who is most likely to benefit from treatment with Avastin, we are left with the totality of the aggregated data. This showed no overall benefit from the addition of Avastin to chemotherapy, even though we may sense that there must be something there to indicate who are the responders from the shape of the curve.  Indeed, after two years, the chemotherapy arm actually did better overall in the AVADO trial, as the arms crossed over.

Dr Len

If anyone wants to read the live public Twitter commentary, I highly suggest you check out Dr Len Lichtenfeld’s (American Cancer Society) tweets from the public hearing – a modicum of thoughtful sensitivity and accuracy in his reporting and colour commentary. He also writes a blog that is well worth reading.  Well done, Dr Len!

Finally, rather than suggest yet another confirmatory trial in metastatic breast cancer at the hearing today, I only wish Genentech had made this offer to the FDA last year when there was more flexibility – a public hearing at your request is hardly the best time for negotiation, but rather a review of the existing evidence.

It isn’t often I agree with the FDA 100%, but in the final analysis they called it correctly on this one.  It’s not over yet though, as FDA Commissioner Margaret Hamburg is expected to make the final decision soon.