GRACE :: Cancer Basics

Search cancerGRACE.org

Dr West

Distinguishing clinical from statistical significance: Are cancer trials aiming high enough to make a real difference?

Share
download as a pdf file Download PDF of this page

Back in August, a press release came out about a new monoclonal antibody against EGFR, called necitumumab, which is a “humanized” antibody that is expected to lead to fewer infusion/hypersensitivity reactions than Erbitux (cetuximab), which is another antibody against EGFR.  This press release from Lilly, the makers of necitumumab, was about the SQUIRE trial, a randomized phase III trial in previously untreated patients with advanced squamous cell NSCLC, in which patients were randomized between cisplatin/gemcitabine with this new agent or placebo.   The press release noted that the trial was positive and demonstrated a statistically significant survival benefit. GREAT!

So why hasn’t there been any discussion of it? First, this agent is remarkably similar to Erbitux, which has been heavily tested and hasn’t found its way into treatment of lung cancer. But the bigger issue may be related also to Erbitux, ,and that is that it highlighted the distinction between statistical and clinical significance. 

Specifically, a trial called FLEX came out several years ago that compared standard chemo with Erbitux to standard chemo with placebo and was actually technically a positive study, showing a survival benefit that was statistically significant. This means that the difference of the two arms  in the primary endpoint, the main variable of the trial, was great enough that there is a less than 5% chance that this is due to random chance alone.

But there is a difference between statistical significance and clinical significance. If a trial is large enough, there can be a statistically significant but actually quite unimpressive in actual terms. Conversely, a smaller trial may fair to be statistically significant but still show results that are extremely promising.  In the case of the FLEX trial, the study showed an improvement in median overall survival of about 5 weeks, which is arguably meaningful, but when you factor in the weekly visits for IV Erbitux, the side effects, and the cost of over $50,000/year for the drug, this agent has failed to lead the world to be sufficiently impressed enough to have Erbitux become a leading consideration in advanced lung cancer.

Now this press report states that there is a significant improvement in overall survival, but the result is as conspicuous for what it omits as for what it includes.  As a general rule, companies don’t sit on good results — if anything, they provide preliminary insinuations of their newest  agent being a “game-changer” (the most nauseatingly over-used term in the world today, I think), but they don’t withhold favorable findings. So when a press report alludes to a positive trial but includes NO information about the actual results in the trial, it’s as much of a red flag as a profile for an online dating site that doesn’t include a photo.  

The press release also says that the full results will be disclosed at a meeting in 2014.  I hope I’m wrong, but I fear that there’s a good reason we didn’t see the results in 2013.  Today, a new drug is judged by the intersection of three criteria: efficacy, side effect profile, and cost, to produce a sense of the value of a drug.  We don’t know the cost yet, but with new cancer drugs averaging a cost of more than $10,000/month now, they need to do better than demonstrate results that are only significant based on statistical analysis.


One Response to Distinguishing clinical from statistical significance: Are cancer trials aiming high enough to make a real difference?

  • cosmo72 says:

    I was on Arm A of the Trial named Inspire of Necitumumab I was on it from Aug 2010 for a total of 30 months which was according to trial team a great result and they were quite excited a trial nurse said I was the longest patient on it
    I got a slight progression in Jun 2012 and had to come of the trial as that was the rules and went on Tarceva
    when I first started the trial the time to progression was 2-3 months and it gradually changed till the latest trial info published was 30 months. At one stage I was told that they were stopping the trial due to some people getting blood clots but this was only affecting people in the early stages when still getting the Cisplatin & Alimta combined with the Necitumumab I was given the choice to leave or stay I stayed.. it was at the time impossible to find out anything about this trial and also to find someone else who was on it (which would have been nice ) I am very gratefull for being on it as the initial Dx was bleak

Leave a Reply

Ask Us, Q&A
Cancer Basics Expert Content

Archives

Share
download as a pdf file Download PDF of this page

GRACE Cancer Video Library - Lung Cancer Videos

 

2015_Immunotherapy_Forum_Videos

 

2015 Acquired Resistance in Lung Cancer Patient Forum Videos

Share
download as a pdf file Download PDF of this page

Join the GRACE Faculty

Lung/Thoracic Cancer Blog
Breast Cancer Blog
Pancreatic Cancer Blog
Bladder Cancer Blog
Head/Neck Cancer Blog
Kidney Cancer Blog
Share
download as a pdf file Download PDF of this page

Subscribe to the GRACEcast Podcast on iTunes

Share
download as a pdf file Download PDF of this page

Email Newsletter icon, E-mail Newsletter icon, Email List icon, E-mail List icon

Subscribe to
GRACE Notes
   (Free Newsletter)

Other Resources

Share
download as a pdf file Download PDF of this page

ClinicalTrials.gov


Biomedical Learning Institute

peerview_institute_logo_243