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Dr West

Dubious ASCO Highlights, BS Endpoints for Ineffective Drugs, and the Credibility Gap

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As many people in our readership know, the ASCO conference is the biggest and most important cancer conference of the year, and there are many competitors for the biggest highlights.  I was therefore annoyed to see that the top-listed highlight in the Medivizor blog description of ASCO highlights, for lung cancer and in general, was about anamorelin, an agent tested to combat cancer-related cachexia (severe weight loss) and associated weakness in patients with lung cancer.

You may note that this agent hasn’t received a lot of mention on the GRACE website or many other media sources.  It doesn’t actually crack the top 100 (and probably not top 250-500) top findings from ASCO.  Why does it merit mention as a highlight in some places? I’d bet good money that they are paid to highlight this work to patients and mislead them into thinking that the “positive” results actually matter.

Bullshit detectorI haven’t really spoken about anamorelin on the GRACE site before, even though their approach represents a lot of what we should disdain about drug development for cancer. My restraint has stemmed largely from the statement ingrained by my mother (and I’m sure by many of your parents as well: “If you don’t have anything nice to say, don’t say anything.” I’ve felt that in the absence of evidence showing some meaningful benefit, anamorelin doesn’t merit the time or effort to discuss it here. I’m certainly not the only one — of the 100 or more lung cancer experts I spoke with at ASCO, anamorelin was mentioned by exactly NONE of them — with good reason. It doesn’t deserve to be on the radar of highlights in lung cancer or any cancer. So why would it be front and center on a patient-oriented ASCO summary? Either anamorelin’s manufacturer paid for it, or the author is very gullible and not qualified to provide commentary about ASCO highlights.

If this placement isn’t an unacknowledged paid advertisement by Helsinn, I must question the obtuse decision to highlight this work. Though the trials with anamorelin were technically positive, showing statistically significant differences in the endpoints they selected, they are remarkably weak endpoints for cancer drugs you’d charge money for. Did patients experience a slight weight increase with 12 weeks of anamorelin? Yes, it went up by about 3 pounds in anamorelin recipients, and it went down by about a pound or two in people who received placebo. They looked for a difference in hand grip strength — a pretty meaningless endpoint that was almost certainly included just to serve as a low bar to exceed, but it failed to do even that. Did patients live better? They found a very slight but statistically if not clinically significant difference in measurements on a scale just related to weight loss. Wow.  Perhaps the only less important endpoint they could have generated is median consumption of anamorelin. These patients didn’t experience an improvement in their performance status or a slowing in the time to clinical deterioration.  There isn’t an iota of a scintilla of evidence that suggests that patients who received anamorelin lived a day longer, despite the teaser statement provided in the Medivizor blog:

Approximately one third of all cancer patients die from cachexia rather than cancer and anamorelin is the most effective drug developed so far which can treat cachexia.

I don’t know if that statement about cachexia being the cause of death in 1/3 of patients is completely made up (there’s no evidence provided to justify that ridiculous contention), but it’s not remotely believable.  It’s like saying that 100% of people ultimately die from their heart stopping or no oxygen getting to the brain.  Cachexia, or cancer-related weight loss, isn’t the primary cause, but a symptom of the real driver, which is progressing cancer. There is NO evidence that anamorelin reverses this process, and it is disingenuous bordering on comically misleading to imply that anamorelin will actually help patients live longer.

Anamorelin isn’t necessarily completely useless, but it represents a class of agents that provide proven benefits only in endpoints that nobody actually cares about. I’ve never had a patient or family member suggest that they don’t care if a patient lives longer but want to slightly improve his hand strength. Does a reversal of weight loss for an absolute difference of 3-5 pounds matter? That might be marginally helpful (though not clearly so if it doesn’t translate into being able to actually live longer or do more in the world other than by precise measurements on meaningless tasks), and I’d be all for it if the cost of anamorelin is <$100/month, but these drugs typically come out at nearly $1000/month, or more, which should imply that they actually provide meaningful benefits and not just improvements that are designed only to generate a statistically positive trial with an otherwise clinically meaningless endpoint.  But then what is trumpeted to patients is a misleading crock of BS that provides a lot of innuendo that anamorelin will improve survival.  That is egregiously overstating its utility, which on its best day might rank in the range of marginal, based on what we’ve seen thus far.

We have enough difficulty struggling over the value of cancer drugs that dramatically improve survival but cost a lot. Why should anyone’s monthly payment for health care go up to pay for a drug that marginally improves someone’s hand grip strength?  Such a drug is worth slightly less than the cost of aspirin, which actually has far more evidence to support a survival benefit against cancer.  

To me, the biggest value in these reports about anamorelin is that it should set off your bullshit detector — anybody touting anamorelin as a highlight from ASCO 2015 is either being paid to do it or is a remarkably poor judge of the relative importance of cancer information.  You should interpret content accordingly.

 


7 Responses to Dubious ASCO Highlights, BS Endpoints for Ineffective Drugs, and the Credibility Gap

  • medivizor says:

    Thanks. In response to your feedback we have updated our report of ASCO – eliminating the review that might be considered highlighting anamorelin. We want to unequivocally state again that we weren’t paid by anyone to report it. However, you have made some excellent points and our reporting might have, unintentionally and unjustifiably, raised the attention to this information. Therefore, we decided to remove it to avoid possibly confusing patients in the debate. We appreciate your calling our attention to it as our objective is to empower and inform patients with great information.

  • linnea says:

    Go Jack! This is the sort of shake the tree advocacy that there is far too little of. As a patient, we tend to believe information from reliable sources (ASCO!) and we (patients) need someone who can parse the good apples from the bad for us. Thank you thank you thank you and keep up the good work.

  • Dr West
    Dr West says:

    Thanks for your comments. Linnea, I really appreciate your encouragement. To clarify, my goal was not to crucify Medivizor, nor to have this be a rant for the sake of ranting.

    I will be happy to acknowledge that Medivizor received no financial incentive for highlighting the data on anamorelin. In that case, we can focus on why the data don’t merit being highlighted, and the danger I see in having any company other other resource paint the benefit of a treatment in excessively rosy terms. It’s not personal. I think it’s a problem when a major newspaper article or TV newscast calls something a miracle against cancer. We see this with all sorts of understudied complementary medicines, or phase 1 or II trials results with various cancer drugs, or lots of other things. I just want us to stay within the realm of what the evidence really shows us.

    -Dr. West

  • linnea says:

    Oh, and please know that by bad apples I mean erroneous and or misleading information (and also not a personal attack!). As patients most of us don’t have the scientific background that you do and it is oh so helpful to have you call out not just the good but the potentially overrated, oversold or just darn wrong information that is out there.

    Keep up the good fight!

  • hopefulbear says:

    I thought the study didn’t even show a treatment effect on hand grip strength?
    http://meetinglibrary.asco.org/content/108575?media=vm

  • Dr West
    Dr West says:

    Sorry — you’re exactly right. The reason I misspoke/mis-wrote is that we shouldn’t even care about such meaningless endpoints if they aren’t a clear, well-correlated proxy for something that actually affects people’s lives.

    -Dr. West

  • catdander forum moderator
    catdander forum moderator says:

    Thank you Jack! As linnea said, it’s good to have someone like you out there shaking the trees.

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