When I read that headline (title of this post) recently, I thought, really? What planet was that clinical trial done on? As I thought more about the content of the article (because you cannot go by headlines, as we all know), I decided I needed to write a “rebuttal” of sorts. Of course, my response here isn’t scientifically based. I don’t have data to prove my points, but I do have a fair number of readers out there who I’m pretty sure would disagree with that headline, and adamantly so. Don’t believe me? Check out this post. The comments keep coming.
First of all, a little summary about the article I am referencing, which was put out by the American Society of Clinical Oncology and presented at the recent ASCO Annual Meeting. The article summarized the results of a clinical trial called the MA.17R. The trial, which was coordinated by the Canadian Cancer Trials Group and partially funded by Novartis, enrolled 1,918 post-menopausal women with early-stage, HR-positive breast cancer and who had received five years of one of the three aromatase inhibitors as initial treatment or after any duration of tamoxifen. The intent was to study disease-free survival (DFS) rates and quality of life (QOL). Participants were followed for a median of 6.3 years. Half received letrozole (Femara) and half received a placebo. Also, interesting to note, Novartis is the maker of Femara.
A second article I want to cite is one titled, Extended AI Therapy Improves DFS in Postmenopausal HR–Positive Breast Cancer, recently published in the ASCO Daily News. I will get to this one later.
So what is disease-free survival?
As stated on the National Cancer Institute’s site, disease-free survival means:
In cancer, the length of time after primary treatment for a cancer ends that the patient survives without any signs or symptoms of that cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works. Also called DFS, relapse-free survival, and RFS.
A few key results of the MA.17R study:
The annual incidence rate of contralateral breast cancer (cancer in the opposite breast) was 0.21% for participants on letrozole and 0.49% on placebo. At five years followup, 95% of women on letrozole were disease free compared with 91% on the placebo. Both findings are considered significant. There were also more bone fractures and more new cases of osteoporosis in the the letorzole group.
However, at five years there was no significant difference in overall survival between the two groups.
And again, taken from NCI’s site, overall survival means:
The length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that patients diagnosed with the disease are still alive. In a clinical trial, measuring the overall survival is one way to see how well a new treatment works. Also called OS.
So basically, overall survival wasn’t impacted and disease-free survival was to some extent.
The study also looked at quality of life and how it was impacted.
This study concluded that QOL was not impacted much differently between the groups, although it was noted there were more vasomotor issues and sexual functioning was worse in the letrozole group. But it wasn’t significant the study summarized. Yep. That’s right.
This is the part that got me all hot and bothered.
Okay, bad pun ‘cuz as many of us know, hot flashes (known as vasomotor symptoms in medical jargon, just fyi) are a major QOL side effect for many women, as is sexual dysfunction. Various nasty side effects women often comment to me about include: loss of libido, vaginal dryness and atrophy, bone loss, weight gain, joint pain, hair loss/thinning, difficulty concentrating, mood swings and fatigue, to name a few.
My observations/concerns about study results:
- What exactly were the questions asked regarding QOL and how were they asked? Both are important.
- Since the study’s participant’s had all completed five years of AI therapy already, perhaps the pool consisted of women who were experiencing fewer and less severe side effects to begin with, which could potentially skew the results.
- I didn’t see a mention about how many women in the study groups had had bilateral mastectomies (but I might have missed it). This component matters (to me anyway).
- I was troubled by the cavalier attitude about bone loss in the second article I cited above. Ian E. Smith, MD, of Royal Marsden Hospital, United Kingdom, stated the following:
“We make a big fuss about this (bone-related toxicities), but the figures suggest it is not a big deal.”
I beg to differ. Speaking as someone who now has osteopenia (my bone health was excellent prior to hormone therapy), bone health is a VERY big deal. This side effect should not be brushed aside. Bone health matters. A lot.
- Troubling side effects deserve validation and also a plan for how to manage them. This isn’t happening a whole lot, or at least not often enough. This is one more reason survivorship plans are so important. And btw, without meaningful survivorship plans and assistance in following them, you can keep your fake, patronizing National Cancer Survivorship days, as far as I’m concerned.
- The 4% difference in disease-free survival is reported as significant, but to an individual patient, an individual woman leading and individual life, I’m not sure 4 points is significant to her.
- I worry that women opting out of taking these drugs for various and personal reasons might be judged even more harshly for not “toughing it out”. (Yes, this happens already)
- 100 deaths occurred in both groups. So again, no difference in OS, but troubling because that’s a lot of deaths. Maybe I’m missing something, but isn’t OS/number of deaths the most important thing?
- Maybe I’ve been on the wrong AI. I suffered horribly on Arimidex. I’m doing better on Aromasin. I wonder how I’d be doing on Femara (letrozole) and if there are similar trials being done on the other two AIs. I hope so because maybe there is a big difference between them as side effects go. My experience so far has been sort of like finding out what’s behind door #1, #2 and #3.
Again, this study concludes that extending AI treatment to 10 years significantly improves disease-free survival without compromising QOL and without OS difference. But of course, this is only one study and its focus was on only one of the three commonly prescribed aromatase inhibitors. It’s not about to become “law” anytime soon.
And to be clear, I am glad these drugs exist; I’m still on one, for crying out loud. But I sure wish we had better options and at the very least, that women received more help in managing side effects when needed. I also hope all three AIs are being looked at and compared for efficacy and QOL impact.
So my question is this: are the conclusions of this study somewhat misleading?
I say yes. The jury is still out on the benefit of extended AI therapy.
As usual, the benefit must be considered along with how an individual woman’s QOL is impacted. Sweeping conclusions/statements about QOL may not be a good idea in this instance.
What do you think?
Are you on one of three aromatase inhibitors and if so, has your QOL been impacted?
Have you started extended AI therapy (the ten-year plan) yet or do you plan to?
Are you on letrozole (Femara) and if so, has your QOL been impacted?