is the SOFT trial under criticism?

Lisey · July 2016

The SOFT trial gave me a lot of hope in their findings, particularly that for node neg/ no chemo / ER+ women who take Tamox alone, 98.6% of them did not have a distant reoccurance in 5 years. I was told the Mayo clinic is disputing the SOFT study... can someone confirm this or point me in the right direction to read more about the criticisms of SOFT? Or is SOFT generally accepted as being an accurate study?

SpecialK · July 2016

This is all I could find, and it is an opinion piece by a Mayo doc.

http://www.ascopost.com/issues/march-25-2015/soft-trial-results-inconclusive-further-study-needed/

Also, thought you might find this second link interesting - it is not related to Mayo, but is a discussion of SOFT and other trials related to OS.

http://jco.ascopubs.org/content/early/2014/10/30/JCO.2014.57.9953.short

Lisey · July 2016

Thanks Special, I'll definitely read these today. It's like following all the tidbits of bread crumbs to get a fuller picture of things.

SpecialK · July 2016

lisey - I am still doing it and I was diagnosed in 2010! Having a fuller understanding has facilitated more meaningful conversation with all of my doctors, and they are very receptive, and has helped me take a clear-eyed approach to my own treatment and given me a more collaborative feeling about my care. Knowledge is empowering but so is trust, and having an up to date, responsive, and flexible oncologist is key to feeling like you're on the same page and getting the best for yourself as an individual. I hope your MO is that kind of doc - from what you have posted it sounds like you are in good hands, and that is your long-term relationship among your team.

BarredOwl · July 2016

Lisey:

I think you may be confused. Are you talking about yesterday when you were trying to reassure someone based on your understanding of the results SOFT study, and they replied that "ATAC was one of the studies criticized by Mayo Clinic and others for genotyping and other errors"?

If that is the Mayo clinic criticism that you are thinking of, please note the following:

(1) Despite the name of the link, this is not a position taken by the "Mayo Clinic" itself, but by a few researchers affiliated with the Mayo Clinic and other institutions.

(2) It does not discuss the SOFT trial results. This is not is not surprising because it was published in 2012, prior to the publication of the SOFT trial results.

(3) Regarding ATAC and BIG 1-98, which it does discuss, the criticism does not relate to the primary results of the original ATAC or BIG 1-98 studies either, but to secondary studies in the patient cohorts from those studies regarding CYP2D6 genotyping, which is an area of intense debate and other researchers have taken strong positions contra. See for example, this Reply taking the opposite position, and their later work on point or this 2015 abstract.

Despite the fact that SOFT and TEXT are relatively recent trials and there may be debate about how best to treat various patients in light of their findings, ASCO has issued a Guideline Update in light of the results of these trials:

ASCO 2016 Update: http://jco.ascopubs.org/content/early/2016/02/11/JCO.2015.65.9573.full.pdf

ASCO 2014 Guideline: http://jco.ascopubs.org/content/early/2014/05/20/JCO.2013.54.2258.full.pdf

BarredOwl

Lisey · July 2016

Barred Owl, Yep, I was lumping them together because I was under the impression the SOFT was a part of the ATAC in some way? Like a subset of those women who are pre-menopause, but all were a part of the larger study no? So I guess if one is called into question, I figured the other would be as well. Am I wrong that they are linked?

I appreciate the links, I'll read the new updates and guidelines.

BarredOwl · July 2016

Hi Lisey:

SOFT and ATAC are completely different trials.

We have (1) SOFT; we have (2) ATAC; and we have (3) a CYP2D6 pharmacogenomic sub-study of performed on some of the patient samples from ATAC. [Edit: Of these,] only item (3) is being criticized in that editorial.

SOFT and ATAC were designed to address the efficacy of various approaches to endocrine therapy in distinct patient subsets. The design and primary outcomes of these two trials are not being criticized in the editorial.

(1) SOFT was a study in 3066 pre-menopausal women and the "results of the planned primary analysis in SOFT comparing adjuvant tamoxifen plus ovarian suppression with tamoxifen alone after a median follow-up of 67 months" were published here:

SOFT (Francis): http://www.nejm.org/doi/pdf/10.1056/NEJMoa1412379

Supplementary Appendix to Francis: http://www.nejm.org/doi/suppl/10.1056/NEJMoa1412379/suppl_file/nejmoa1412379_appendix.pdf

(2) ATAC was a study in 9366 post-menopausal women regarding Anastrozole alone or in combination with tamoxifen versus tamoxifen alone:

http://www.ncbi.nlm.nih.gov/pubmed/12090977?dopt=Abstract

(3) A sub-study of ATAC (Rae et al.) used archived materials collected from a sub-set of the post-menopausal patients who participated in the ATAC trial were used to assess the potential import of CYP2D6 genotype, as reported here:

http://jnci.oxfordjournals.org/content/104/6/452.full.pdf

"We designed a genetic substudy that represents patients enrolled in the ATAC trial only in the United Kingdom but were compared with all other patients (rest of the world [ROW]) . . ."

==> The editorial is only taking issue with the pharmacogenomic sub-study, i.e., item (3) the sub-study of ATAC regarding CYP2D6. It is not criticizing the original studies, items (1) and (2) or their findings (not the least because (1) was published several years later).

BarredOwl

solfeo · July 2016

Lisey, you originaly mentioned SOFT in the other thread, then later corrected yourself, "Also, I meant the ATAC studies rather than the more specific SOFT studies... "

My answer then applied to ATAC. As for everything else, what BarredOwl said.

The bottom line that we have repeated many times, is that the issue of CYP2D6 genotyping is undecided. You're not going to find anything that proves it one way or another. What you have available is a body of evidence to be weighed, and a personal decision to make regarding which evidence feels more meaningful to your situation. You can't base it on any single study, you have to look at everything in total.

And BTW, every study will be criticized by someone somewhere for some reason, so you can't even use the criticism alone as a deciding factor without weighing all of the evidence together. The scientific method is fairly objective (or is supposed to be) but interpretation of the results is often very subjective.

Lisey · July 2016

Solfeo, my biggest misunderstanding was thinking when you said the ATAC was under scrutiny, I thought that applied to the SOFT as well because I wrongly believed it was a subset that they expanded into it's own study. My mistake on that.

is the SOFT trial under criticism?

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