TAILORX trial results Monday, September 28

Moderators

Hey All,

Our editors just prepared this research news on the topic. Take a look:

Research Confirms Oncotype DX Test Score Between 0 and 10 Means Women Can Skip Chemotherapy

The Oncotype DX test is a genomic test that analyzes the activity of a group of 21 genes that can affect how a cancer is likely to behave and respond to treatment.

Doctors use the Oncotype DX test to help figure out a woman's risk of early-stage, estrogen-receptor-positive breast cancer coming back (recurrence), as well as how likely she is to benefit from chemotherapy after breast cancer surgery.

A second test, the Oncotype DX DCIS test, analyzes 12 genes and helps doctors figure out a woman's risk of DCIS coming back and/or the risk of a new invasive cancer developing in the same breast, as well as how likely she is to benefit from radiation therapy after DCIS surgery.

Most early-stage, estrogen-receptor-positive breast cancers that haven't spread to the lymph nodes are considered to be at low risk for recurrence. After surgery, hormonal therapies such as an aromatase inhibitor or tamoxifen are prescribed to reduce the risk that the cancer will come back in the future. Whether or not chemotherapy also is necessary has been an area of uncertainty for patients and their doctors. The Oncotype DX test was designed to offer more information to help women and their doctors make decisions about chemotherapy.

The Oncotype DX test results assign a Recurrence Score -- a number between 0 and 100 -- to the early-stage breast cancer. You and your doctor can use the following ranges to interpret your results for early-stage invasive cancer:

• Recurrence Score lower than 18: The cancer has a low risk of recurrence. The benefit of chemotherapy is likely to be small and will not outweigh the risks of side effects.
• Recurrence Score between 18 and 31: The cancer has an intermediate risk of recurrence. It's unclear whether the benefits of chemotherapy outweigh the risks of side effects.
• Recurrence Score greater than 31: The cancer has a high risk of recurrence, and the benefits of chemotherapy are likely to be greater than the risks of side effects.

A prospective study shows that women with an Oncotype DX test Recurrence Score between 0 and 10 can safely be treated only with hormonal therapy, allowing them to skip chemotherapy.

The study was published online on Sept. 28, 2015 by the New England Journal of Medicine. Read "Prospective Validation of a 21-Gene Expression Assay in Breast Cancer."

A prospective study follows a group of similar people who are different in terms of the factors being studied to see how the factors affect the rates of a certain outcome.

In this study, called the TAILORx (Trial Assigning IndividuaLized Options for Treatment), included more than 10,000 women diagnosed with early-stage, hormone-receptor-positive breast cancer that hadn't spread to the lymph nodes. The researchers performed Oncotype DX texts on tissues samples from all the cancers and all the women were then assigned an Oncotype DX Recurrence Score:

• women with a Recurrence Score of 0 to 10 were assigned to receive hormonal therapy alone (meaning they didn't get chemotherapy) -- 1,626 women were in this group (15.9% of the women in the study)
• women with a Recurrence Score of 11 to 25 were randomly assigned to received either:
  • chemotherapy plus hormonal therapy
  • hormonal therapy alone
  6,897 women were in this group (67.3% of the women in the study)
• women with a Recurrence Score of 26 or higher were assigned to receive chemotherapy plus hormonal therapy -- 1,730 women were in this group (16.9% of the women in the study)

Earlier studies have shown that women with a Recurrence Score of 10 or lower had good outcomes when treated with hormonal therapy alone and that women with a Recurrence Score of 26 or higher benefitted from chemotherapy and these benefits outweighed the risk of side effects. It's been unclear whether women with a Recurrence Score of 11 to 25 would benefit from chemotherapy, which is why the researchers randomly assigned the women in this group to hormonal therapy alone or hormonal therapy plus chemotherapy.

The women with a Recurrence Score of 0 to 10 were treated with different types of hormonal therapy:

• 59% of the women took an aromatase inhibitor
• 34% took tamoxifen
• 1% took tamoxifen first, then switched to an aromatase inhibitor
• 3% took medicine to stop their ovaries from making estrogen

After 5 years, less than 2% of the women had the cancer come back (recurrence). Overall survival -- how many women were alive with or without the cancer coming back -- also was 98%.

The researchers who did the study said the results provide the highest level of evidence that an Oncotype DX Recurrence Score of 0 to 10 means that those women can safely avoid chemotherapy.

"The compelling results seen in this global study provide unequivocal evidence supporting the clinical utility of Oncotype DX to risk-stratify patients with early-stage breast cancer, and indicate that the findings are generalizable to everyday clinical practice," said lead author Joseph A. Sparano, M.D., vice-chairman of medical oncology at Montefiore Einstein Center for Cancer Care, and professor of medicine and of obstetrics, gynecology, women's health at Albert Einstein College of Medicine. "This is the first prospectively conducted clinical trial evaluating this assay -- or any multigene expression assay for that matter -- in which patients with early stage breast cancer were uniformly treated based on their assay results. The findings provide the highest level of evidence supporting expert-derived clinical practice guidelines which have recommended Oncotype DX in patients with early stage ER-positive breast cancer."

The researchers will continue to follow the women in the study to determine whether women with a Recurrence Score of 11 to 25 also can skip chemotherapy or whether they benefit from it.

"For those seeking confirmation that this assay can identify a cohort of patients who should be spared chemotherapy, this result is both reassuring and frustrating," said Clifford Hudis, M.D., chief of the Breast Cancer Medicine Service at Memorial Sloan-Kettering Cancer Center, in an invited commentary that was published along with the research article. Dr. Hudis also is a member of the Breastcancer.org Professional Advisory Board.

He continued, "For patients in this new 'lower risk' group, it is clearly helpful, if broadly anticipated. However, for the many physicians already using the test, the gap between this cutoff point of 10 and the higher 'standard' cutoff point of 18 may be a concern. Some others will wonder whether chemotherapy is beneficial or indicated even in patients with scores up to 25. If chemotherapy is effective in this newly defined intermediate-risk group (score 11 to 25), then examination of the subgroup of patients with scores of 11 to 17 will be critical, since there will be two conflicting guides to their treatment that need to be reconciled: the cutoff point used in this trial and the previously available cutoff point that is associated with the commercial test."

If you've been diagnosed with early-stage, hormone-receptor-positive breast cancer and are weighing the pros and cons of adding chemotherapy to your treatment plan, the Oncotype DX test may help you and your doctor make that decision. Besides any genomic test results, you and your doctor will consider other factors when developing your treatment plan, such as:

• your age
• the size of the cancer
• hormone receptor protein levels
• the grade of the cancer
• any other health conditions you have
• your personal preferences

Together, you can make the best treatment decisions for YOU!

You can learn more on the Breastcancer.org Oncotype DX Test page.

Published on September 30, 2015 at 6:03 AM

doxie

Moderators,

Thanks for jumping on this. I'll let someone else dig through the details. But I want to take this moment as an opportunity to ask you to correct an error running through much of your text BC.org on the OncotypeDx risk ranges. You keep stating that high risk starts at above 31 and medium up to and including 31. The Oncotype site states that high risk starts at "greater than or equal to" 31. The symbol they use is the > with a _ line below. (don't know where to find that in the browser I'm using). Here is a ink to this information noted on their site in two graphs. http://breast-cancer.oncotypedx.com/en-US/Professional-Invasive/RecurrenceScoreResults/PrognosticPredictiveInfoForNodeNegativePatients.aspx

voraciousreader

I am going to once again add to what the moderators published. The folks that made the OncotypeDX test also were interviewed and I think their point of view needs mentioning again with respect to Sloan Kettering's Dr. Hudis.

###############################$######$$=======

"Without data on the ultimate outcomes of these patients, drawing a conclusion on what these discrepancies mean has been impossible. Unfortunately, the current analysis of TAILORx has not yet delivered the awaited outcomes data for the randomized intermediate RS subcohort that could help answer some of these questions.

Steve Shak, chief scientific officer of Genomic Health, told GenomeWeb that this is because there simply haven't yet been enough recurrences or other events in this subset to exclude or confirm a benefit from chemotherapy.

"The data monitoring committee advised that [the researchers] need to continue to follow those patients and that they will inform them when that [intermediate RS] analysis can be done," he said. "The understanding … is that it's taking longer because the event rates are low, which would be great news for patients."

https://www.genomeweb.com/molecular-diagnostics/ta...

Hopeful82014

VR - I agree that the lack of "events" among the intermediates is extremely important. To me it's almost as significant and intriguing as the news about those with a low score. Thanks for reiterating it.

Kathy044

Another way of looking at the the lack of 'events' in the subsets so far is how great endocrine therapy is working for women with hormone positive, node negative cancers. I think that should be the headline for the women in the 1 to 10 subset rather than that of no need for chemo.

Kathy

voraciousreader

yes...hope!

And....

Yes Kathy!

At first I was worried that there wouldn't be enough recurrences ...so there wouldn't be statistical significance. However, it appears that that was the greatest news coming out of the study. So, Hope and Kathy....yes! And yes!

Mods....any chance of modifying your column? Dr. Hudis's statement is half the story....the other half is more noteworthy.

Hopeful82014

"Mods....any chance of modifying your column? Dr. Hudis's statement is half the story....the other half is more noteworthy."

Not only more noteworthy, but also more likely to be overlooked or even misrepresented or downplayd by the mainstream press, which may not understand the significance of the news.

Anonymous

Wonder how long it will take for U.S doctors to accept the Oncotype and stop doing chemo when it will not help? Recently, info was released that chemo does not increase survival time in Stage 4 cancers and we still see so many Stage 4 cancers get chemo. Also, thanks JohnSmith love your comments.

ShetlandPony

What info was released about stage iv and chemo, Aug? I don't want to go off the topic of this thread, but I can't just let your statement pass.

BarredOwl

Hi:

There was a recent report about chemotherapy use in a variety of solid tumors (not specifically breast cancer) that received some press coverage. However, it was conducted in a specific subset of stage IV patients near end of life (with "end-stage cancer") as defined in the "Sample" section of the paper, and does not appear to stand for the broader proposition above. With a variety of solid tumors, varying regimens, and specific patient subset, this particular study (if it is the one in question) was not designed to address the survival benefit of any particular chemotherapy regimen in the setting of stage IV breast cancer.

Original article (a paywall may be erected shortly, so if you're interested, read it now):

http://oncology.jamanetwork.com/article.aspx?artic...

The related commentary is partially available:

http://oncology.jamanetwork.com/article.aspx?artic...

And of course, a NYT article:

http://www.nytimes.com/2015/07/24/health/chemother...

If this is of interest, it might warrant a separate thread in another forum.

BarredOwl

Nash54

On the subject of intermediate scores....since there is a lack of recurrence thus far for both groups of women (chemo/no chemo ) if this trend continues what would the conclusion be?   

voraciousreader

Nash....hopefully the conclusion will be that the risk of chemo will be greater than the benefit....soooooo... More sisters in the intermediate score range can skip chemo and rest assured that endocrine therapy is the way to go..

Nash54

Thanks VR....I was hoping that was the case.  I was a 24 and no chemo so that would be reassuring 👍

voraciousreader

sleep well, Nash.... I can't help but think back to the Atlas study confirming that for many, not all, but many...10 years of endocrine therapy successfully reduces recurrence. This important study was released two years ago....it seems to me that endocrine therapy is a very potent weapon. Likewise, for those who have high OncotypeDX scores, chemo seems to be, for those sisters, their best friend along with endocrine therapy.

I'm starting to wonder that in 5 years, will we be seeing less chemo used for HER2 NEGATIVE AND ER sisters and better mortality...I think we are entering an exciting phase....that said...we still have sisters coming out of the gate with Stage IV despite population based screening. We all deserve a better screening method. Will liquid biopsy screening be not too far ahead making present date imaging obsolete? Hmmmmm.....

Sloan15

voraciousreader, thanks for keeping up on this. I'm thinking of not doing my LAST chemo because of SE. My onc score is estimated in the intermediate area, and I might get the test done and skip the rest of chemo.

123JustMe

VR, is there a link to the atlas study on BCO? I would love to look at it. Thx.

MelissaDallas

123justme, here's a link

http://www.thelancet.com/journals/lancet/article/P...(12)61963-1/abstract

voraciousreader

http://www.medscape.com/viewarticle/775683

voraciousreader

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC359606...

Here are the results of the ATTom study that piggybacks ATLAS

voraciousreader

sloan....in all fairness....these results are very new and need digesting before treatment guidelines change. I'm sorry you are having treatment side effects. Talk to your team and see what they say....good luck

voraciousreader

http://www.medscape.com/viewarticle/805171

voraciousreader

http://www.onclive.com/web-exclusives/ASCO-Guideli...

123JustMe

Thanks for the info VR.

PoohBear-61

Voraciousreader ......I thought id pick your brain since you are extremely knowledgeable about these trials ....

Ive been reading up on the ATLAS trail and found the following comment .....

In ATLAS, 6,846 women in 36 countries with ER-positive disease who had five years of adjuvant tamoxifen were randomly assigned between 1996 and 2005 to continue another five years (to year 10) or stop at year five. Half had node-positive disease. Annual follow-ups recorded compliance, hospital admissions, breast cancer recurrence (including new contralateral), any other new primary cancer, and cause of death.

My Question is ....If half had node positive disease ...is there information regarding the women that relapsed in the 5 year arm vs the 10 year arm ......as in.... were they mostly the node positive group that relapsed ...and if so then the small benefit from the added 10 years would only benefit the node positive group ?... not sure if i am making any sense ?? ....I overthink things sometimes !

Molly50

So if I'm reading the Asco study correctly it's not recommended to be on AI's for longer than 5 years but you could follow it up with 5 years of Tamoxifen for post menopausal women?

123JustMe

That is how I read the study....

voraciousreader

ok! Sisters!!! Very busy today....so I can't contribute now. That said....I'm going to give all of you an assignment that might help in answering all of your great questions!

Go on the NCCN's website and look for the professional version (red logo) of the breast cancer treatment guidelines and scroll down around 100 pages and read in the DISCUSSION section about the topic of ENDOCRINE THERAPY. The reason why it is sooooo important to read is because they talk about all of the endocrine studies and their limitations...

Furthermore....a little more homework....once you have read this year's guidelines, go back and read several years of the guidelines regarding ER+ HER 2 negative tumors. Those guidelines are found around page 25....I can't specifically lead you to a specific page, because, each year varies. However, it is EXTREMELY important to read several years of guidelines because you will be looking for trends...

Note, in 2011, the NCCN guidelines first recommended the OncotypeDX test.

I hope many of your questions will be answered as you carefully read the guidelines.

Please report back and I will report back too!

voraciousreader

ok! Just downloaded 2015 NCCN breast cancer treatment guidelines....it is the"enhanced preliminary" version.....begin reading a few pages before page 87. From page 87, it discusses systemic endocrine therapy... A few pages before page 87, it discusses TailorX.....

voraciousreader

pooh....hope this answers your question...

"Well-established clinical factors including tumor size; nodal status; ER, PgR, and HER2 biomarkers¹⁶; and molecular diagnostic assays¹⁷ serve as prognostic factors for breast cancer recurrence. However, there are no robust specific clinical or biomarker measures that selectively predict early versus late recurrence, nor predict whether tamoxifen or AI therapy would be appropriate treatment, nor determine whether longer durations of adjuvant endocrine therapy are clinically indicated. Identifying such markers is an important research priority. Extensive clinical data, specifically including data from trials of extended adjuvant treatment, indicate that smaller and/or node-negative cancers are at lower risk for recurrence after 5 years of adjuvant endocrine therapy than are larger and/or node-positive tumors.^9,18–21 For this reason, the magnitude of benefit of extended durations of adjuvant therapy is certainly lower for patients with stage I cancers than for those with higher stage tumors. Although patients with favorable prognosis tumors may experience more risk than benefit with extended adjuvant treatment, the clinicopathological factors for defining such patients are not established. Some of the benefit of extended adjuvant treatment is derived from prevention of in-breast recurrences and/or second cancers.^9,18–22 Women who have undergone bilateral mastectomy are not at risk for these occurrences, reducing their likely benefits from extended therapy. Considerations of benefit and risk on the basis of stage and the adverse effects experienced by a given patient may help clinical teams make individualized recommendations on the appropriateness of ongoing treatment for a specific woman."

http://www.thelancet.com/journals/lancet/article/P...(12)61963-1/fulltext

Molly...you are correct. That said, my onc said 10 years of endocrine therapy before the ATLAS results were reported. He said as long as I felt okay, he wanted me to CONSIDER 10 years. He didn't care how I mixed it up.....I welcome the continued results of the studies, including SOFT and TEXT.

voraciousreader

http://m.jco.ascopubs.org/content/32/21/2255.full