I didn’t attend the this year’s ASCO (American Society of Clinical Oncology) meeting, which wraps up today. The reason is simple. I had attended the Society of Surgical Oncology (SSO) and the American Association for Cancer Research meetings in March and April, respectively. ASCO was just one meeting too many in too short a time. Also, I’m a surgeon, and ASCO tends to be a bit more medical oncology-oriented, with lots of presentations of trials testing this chemotherapy regimen against that chemotherapy regimen for cancers I don’t treat, like the various leukemias. Still, this year, I kind of wish I had attended, because the results of a trial (the TAILORx trial) were being presented, and those of us who specialize in breast cancer have been waiting for a long time. I also wanted to discuss the results of this trial as a rebuke to certain alternative medicine mavens who claim that all we cancer doctors want to do is to cut, poison, and burn—but especially poison. After all, if you peruse certain websites, you might get the idea that oncologists are anxious to poison people with cancer using toxic chemotherapy regimens. Basically, the TAILORx trial has defined a rather large subgroup of breast cancer patients who do not benefit and therefore do not require chemotherapy. The details will follow, but first let’s back up a bit.
I’ve discussed the difference between primary treatment and adjuvant treatment with chemotherapy on a number of occasions. Indeed, confusing the difference is one of the main reasons why testimonials for cancers treated primarily surgically can sound convincing to those not familiar with cancer biology and treatment. Basically, curative chemotherapy is administered as a primary treatment for a specific cancer. Leukemias and lymphomas tend to be treated primarily with chemotherapy ± radiation (in the case of lymphomas, mainly). Organ tumors, like colorectal cancer, breast cancer, and the like, tend to be treated primarily surgically by extirpation of the cancer and part or all of the affected organ. Through decades of clinical trials for such cancers, it’s been shown that the addition of adjuvant chemotherapy after surgery can decrease recurrence and increase the rate of overall survival. In other words, chemotherapy is “icing on the cake” that decreases the chance of the cancer coming back and killing the patient. This is why so many alternative cancer cure testimonials can sound convincing. When, for instance, Christ Wark beat colon cancer or Suzanne Somers or Hollie Quinn did well after treating their breast cancers with “holistic” treatments, in reality, it was the surgery that they both underwent that “cured” them. Refusing adjuvant therapy, be it chemotherapy in Wark’s case or Tamoxifen in Suzanne Somers’ case, only increased their risk of recurrence. They were lucky enough, however, that that increased risk didn’t manifest itself in a recurrence in their specific cases.
So how does this relate to the TAILORx trial, which was reported over the weekend at ASCO and published early in the New England Journal of Medicine? The stereotype among alt med mavens of oncologists just drooling at the prospect of injecting cancer patients with all manner of horrific toxic chemotherapies feeds into the reasons why patients above were susceptible to the siren songs of quacks and decided to eschew evidence-based treatment for their cancers. Of course, part of the problem with adjuvant chemotherapy for breast cancer is that most of the women who receive it don’t benefit from it. If you take two large groups of women with breast cancer, well-matched for age, tumor type, race, and other factors relevant to how well they do with breast cancer, and then randomize them either to receive chemotherapy or not after their curative surgery for breast cancer, on the whole, the group receiving chemotherapy will have better five year and ten year recurrence-free and overall survival. However, most of those women would have done well anyway, and some would die regardless if they had chemotherapy or not. In only a relatively small percentage of them does chemotherapy make the difference between living and dying. That percentage depends on the pre-chemotherapy risk of recurrence, such that the absolute percentage of women saved by chemotherapy increases in nastier cancers, where the risk of recurrence is higher, but that doesn’t change the essential problem. Toxic therapy is being administered to some women without benefit. Despite this problem, most women for whom chemotherapy is recommended do undergo the treatment, even when the expected survival benefit is in the single digit percentages. It’s also hard to argue with results. Over the last 30 years, mortality from breast cancer has declined by nearly 40%, thanks in large part to better adjuvant treatment regimens after surgery. The authors note the problem the study was designed to address:
Hormone-receptor–positive, axillary node–negative disease accounts for approximately half of all cases of breast cancer in the United States.2 Adjuvant chemotherapy reduces the risk of recurrence,3-5 with effects that are proportionally greater in younger women but that are little affected by nodal status, grade, or the use of adjuvant endocrine therapy.6,7 These findings led a National Institutes of Health consensus panel to recommend adjuvant chemotherapy for most patients,8 a practice that has contributed to declining breast cancer mortality.9 However, the majority of patients may receive chemotherapy unnecessarily.
Yes, one of the most pressing questions in breast cancer for the last few decades has been how to identify which patients will and won’t benefit from chemotherapy, or at least to develop predictive tests that make our assessments of who will and won’t benefit from adjuvant chemotherapy more reliable and accurate. That’s what TAILORx is about. Before you can understand TAILORx, you need to understand a bit about estrogen receptor-positive, HER2-negative, node negative breast cancer, which makes up roughly half of all breast cancer cases diagnosed, and the OncoType DX test (also known as the 21-gene recurrence score assay). This particular assay has revolutionized the treatment of this form of breast cancer, which can be treated by hormonal therapy to block estrogen activity with drugs such as Tamoxifen or aromatase inhibitors.
Basically, the OncoType test is a PCR-based test that measures the levels of 21 genes in the tumor. The genes measured involve estrogen signaling, control of proliferation, and housekeeping genes for normalization. The history of how this test was developed and validated is too long and complex for purposes of this discussion; so I’ll boil down the results. Based on the levels of the various genes, a “recurrence” score is calculated ranging from 0-100 from which the patient’s risk of distant recurrence (metastasis) within 10 years can be estimated. (Note that this estimate assumes that the patient receives adjuvant hormonal therapy, either Tamoxifen or an aromatase inhibitor). The bottom line is that patients with a low recurrence score (17 or lower, and definitely 10 or lower) do not benefit from adjuvant chemotherapy, while those with a high recurrence score (31 or greater) do. The problem is that what to do with patients with an intermediate recurrence score (18-30), which is a large number of patients. Chemotherapy is usually recommended for most of these women. Now here’ the thing. Even with these limitations, the adoption of Oncotype testing has already decreased the use of chemotherapy in this patient population quite markedly. (Take that, Mike Adams!)
Enter TAILORx, which was designed to answer the question of where the OncoType recurrence score cutoff should be for recommending chemotherapy. TAILORx is a four-arm clinical trial, in which women were assigned to groups this way after surgery:
- Recurrence score of 10 or lower (low risk): Hormonal therapy only.
- Recurrence score of 26 or higher (high risk): Chemotherapy and hormonal therapy.
- Recurrence score 11-25 (intermediate risk): Randomize to either (1) hormonal therapy only or (2) hormonal therapy and chemotherapy.
Here is the way patients were assigned:
So, based on the 10,273 subjects who were assigned or randomized, here is the result:
There you have it. There was no difference in disease-free survival or distant recurrence. None, nada, zip:
In the intention-to-treat population, endocrine therapy was noninferior to chemoendocrine therapy in the analysis of invasive disease–free survival (hazard ratio for invasive disease recurrence, second primary cancer, or death [endocrine vs. chemoendocrine therapy], 1.08; 95% confidence interval [CI], 0.94 to 1.24; P=0.26) (Figure 2A). Endocrine therapy was likewise noninferior to chemoendocrine therapy in the analyses of other end points, including freedom from recurrence of breast cancer at a distant site (hazard ratio for recurrence, 1.10; P=0.48) (Figure 2B), freedom from recurrence of breast cancer at a distant or local–regional site (hazard ratio for recurrence, 1.11; P=0.33), and overall survival (hazard ratio for death, 0.99; P=0.89).
And:
In this prospective, randomized trial, we found that among 6711 women with hormone-receptor–positive, HER2-negative, axillary node–negative breast cancer and a midrange recurrence score of 11 to 25 on the 21-gene assay, endocrine therapy was not inferior to chemoendocrine therapy, which provides evidence that adjuvant chemotherapy was not beneficial in these patients. This finding contrasts those of previous biomarker validation studies that were performed retrospectively with the use of archival tumor specimens, in which a substantial benefit for the prevention of distant recurrence has been found for the combination of chemotherapy and endocrine therapy in patients with a recurrence score of 26 or higher.12,13 The 9-year rate of distant recurrence in women with a recurrence score of 11 to 25 in our trial was approximately 5%, irrespective of chemotherapy use, a finding consistent with that predicted from the original report showing a significant treatment interaction between chemotherapy benefit and a recurrence score of 26 or higher.14 Updated results for patients with a low recurrence score of 10 or less, who were previously reported as having a 1% distant recurrence rate at 5 years in our trial,18 now indicate a 9-year rate of distant recurrence of approximately 3%.
The authors also did some exploratory subgroup analyses to determine if there might be benefit due to chemotherapy in specific subgroups. They did find that younger women with a recurrence score less than 25 might still benefit from chemotherapy under certain conditions:
The results of our trial suggest that the 21-gene assay may identify up to 85% of women with early breast cancer who can be spared adjuvant chemotherapy, especially those who are older than 50 years of age and have a recurrence score of 25 or lower, as well as women 50 years of age or younger with a recurrence score of 15 or lower. Ongoing clinical trials are obtaining additional information on the clinical usefulness of the 21-gene assay in women with hormone-receptor–positive breast cancer and positive axillary nodes33 and evaluating the clinical usefulness of the 50-gene assay in this context.34
That’s right. Oncologists and scientists already have their eyes on another group of women who might be able to forego chemotherapy after surgery for breast cancer, women with cancer in one or two lymph nodes, all of whom currently receive a recommendation for chemotherapy now, barring medical contraindications. There’s also another test out there (the MINDACT) that used a different gene test, the MammaPrint. It’s not as widely used as OncoType (yet), but has the advantage of having been validated for more than just hormone receptor-positive cancers. I discussed the MINDACT trial back when it was published in 2016.
The bottom line is that, contrary to the stereotype quacks promote of oncologists, we don’t like the status quo, in which many women who won’t benefit from chemotherapy receive it anyway because we know chemotherapy saves the lives of some women but haven’t had good tests to predict which women will benefit and which women will not. As I’ve said before, while it is true that there are a lot of women who receive chemotherapy who probably didn’t need it, it’s not because oncologists want to give lots of chemotherapy, and it’s not based on profit motive. It’s because we couldn’t predict which of these women will benefit from chemotherapy. Gene tests like the OncoType and MammaPrint are now changing that. At the very least, we can now predict, albeit not 100% by any means, which individual women are highly unlikely to benefit from chemotherapy, and oncologists are acting on that knowledge. And guess what? Oncologists don’t mind at all. In fact, they like it. It turns out that cancer doctors don’t like to administer chemotherapy to women who are very unlikely to benefit from it and continue to work on ways to reduce that number and make sure only the women who are likely to benefit from chemotherapy receive it. As a result of TAILORx, thousands of women who would have received a recommendation for chemotherapy in the past will be able to forego chemotherapy.
Take that, Mike Adams!
32 replies on “Take that, Mike Adams! The TAILORx study vs. the alt-med stereotype of oncologists anxious to administer toxic chemotherapy”
The problem is not that what you say is not right. It’s obviously rather right. The problem is that there can be a dual reading of this finding: 2 to 3 times more people didn’t benefit from chemiotherapy, if I’m broadly correct. In and of itself, it can be construed as confirmatory evidence of overtreatment.
The only way to judge which interpretation is right would, in my opinion, be to estimate quality of life adjusted life expectancy in both cases: absence of chemio on the whole group, and chemio in the whole group. I do not know what data there is to answer this question.
However, even this quantification would not deal with the moral hazard that would be induced by the perspective of not treating sick patients for the benefit of not treating “healthy” patients. While this study does allow progress on the topic, the moral hazard issue is mostly left to various appreciations of morality. Morality of doctors and alt-medecine morality here are antagonists. And it’s not only a question of data: the fact is that there were unnecessary treatments for the benefit of sick people. Fact on which everybody agrees, with dual and antagonist moral interpretations of the same fact.
Maybe I’m wrong on my appreciation of the dual impact of “morality” and evidence in these decisions. Would appreciate being contradicted.
But I have another question on this study: whether this research finding can be safely translated to practical day to day medicine. As of today I do wonder whether or not the cutoff score is precise enought as a diagnostic tool not to induce too much false positives and false negatives on both sidea of the cutoff. Because that would likely again negatively impact the moral hazard issue.
Quality of life is hard to quantify. Are patients being over treated? Certainly but they knew that when they started the study.
Quality of life is going to have to be part of the risk vs benefit analysis that the PATIENT does when chemotherapy is recommended based on their recurrence score. Knowing how likely they are to have that risk will make that analysis easier. Quite frankly, now that there are guidelines for when NOT to include chemotherapy, I don’t see a lot of women in the grey area, especially towards the low end of it (scores towards 18) opting to get chemotherapy if their genetic testing indicates it’s not necessary. That will take care of the problem of over treatment.
For women with higher recurrence risk scores, it becomes more of an issue of when to enter hospice care if their 5 year survival rate is in the single digits. We might be providing treatment to them that will offer no benefit, as is happening now, but that’s an issue with all sorts of diseases such as CHF, COPD, and renal failure. Better understanding of outcomes can help us advise patients, but the decisions are ultimately up to them.
Decisions are ultimately up to them? Yes and no. There’s a concept of mental capacity to make informed decisions, and among other factors, its interpretation depends from country to country. That’s one way among others moral hazard creeps into the equation.
Well, I certainly have to base things off how things are done in the United States, since that’s where I live.
And most developed countries advocate informed consent to medical treatment. Under developed countries don’t have the same kind of access to this level of care unless you’re rich, but I’ve never heard people being forced to take chemo therapy. I suppose it could happen; I’m just not aware of it.
As a nurse, my role is not to make my patients decisions for them. I give them the best medical information I can, and they make their own decision. I then support them as best I can. I do believe it’s important for me as a nurse to be up to date on the state of medical care, because all too often, patients nod their heads at the doctors like they understand, then turn to me after the doctor leaves and ask, “So what did he just say?”
It’s not that doctors are poor at educating patients (though some are). It’s that the information often takes some time to process. I help them with that.
If a patient’s mental capacity is so diminished that they cannot make an informed one, then my duty is to notify the ethics board of my hospital. Beyond that, yes, they make their own decisions. I can’t know everything about their lives to say with certainty they are making the wrong choice just because it’s not what I would do, or what most people would do. Unless they’re spouting woo, there’s probably a factor I don’t see.
I don’t agree with your interpretation. This is about predicting unnecessary. To do that requires tests with reliable metrics. Judging unnecessary with the benefit of hindsight is a completely different sort than predicting it.
I agree. I’m not conflating these two issues even if it may seem like it at first glance. Moral judgement a posteriori and evaluation a posteriori are indeed two different things. They abide by different methodologies. If you’re confusing them, do not be surprised if natural news will indeed confuse them too. Which will happen. This study is both a major progress and nonetheless also a way to allow quacks to aim a headshot at “allopathy”.
well mr orac…better get the latest info from down here in oz all over the media 70% reduction in chemo as treatment for breast cancer going forward due to many imuno tharapys in use now ..merk sharpe dome have just bought out 100% of a sydney based /oz co called..viralytics.com on the asx who have developed …cavatak…this is a silver bullet.. msd will introduce it to the world along with there keytruda protocol as the main up front defence for this and many other cancers …the end for the standard chemo one type fits all is over & along with cannabis oils will be the big hitters …..leaving a lot of quackers out of the game …. the thing is getting out to the punters whats going on …. with positive news when we find it if still is up go to this companys web site & go to there media section there is a 6minute vidio made in australia by the a.b.c. that tells a interesting cancer persons story … cheers happy bob ..8 in oz
And in English?
How about any language? This is gibberish. I have no idea what you are saying.
Perhaps he used to much of the product he seems to be promoting?
Well, that was incoherent.
Still I think he’s trying to say that immunotherapy and the use of viruses to infect tumors and cause cell death are going to replace chemotherapy.
That may well be true, but the drugs he discusses were originally targeted to melanoma, not breast cancer. Cavatak is still in clinical trials, though it seems promising. I’m sure Orac would know more about that than I would, or SpongeBob here.
And you know, I’m fine with the idea of developing new drugs that will replace traditional chemotherapy if they’re more effective and less toxic. I think any healthcare provider would be. But until they’re ready for prime time, chemotherapy is what we’ve got. If I developed breast cancer, I would get the surgery and do the chemo, if that’s what my surgical oncologist recommended to me. The survival rates have improved greatly, and unless I’ve got stage IV with mets, I’d probably benefit making it worth it.
But as for cannabis oil; sorry Sponge Bob. No evidence it does shit for cancer. People are not petri dishes. Whatever value it may have in pain management (arguable) or appetite enhancement is the only benefit it has for a cancer patient.
Interesting that the Viralytics people are shifting the emphasis of their clinical trials away from Cavatak on its own, towards a Cavatak / Keytruda combination. This could be an admission that their oncolytic virus doesn’t actually do much in isolation. Mind you, it could also have been a sweetener for the company’s acquisition by Merck, what with Keytruda being a Merck product, and Merck’s finances being in a sad state unless they can grow the Keytruda market.
Also relevant: A small Australian start-up like Viralytics has no problem going through the whole imbroglio of clinical testing, Phase 1 and 2 and 3 trials. Belying the scammers like Burzynski and Rigvir, and their claims that clinical trials of their magic leprechaun jism are financially impossible so they have no alternative but to sell the stuff to suckers untested.
I’m having trouble accepting that these are real trade names.
They do sound more like characters in a Jack Vance novel.
Ok Robert, I’ll give this a go.
1) “the standard chemo one type fits all ” Did you not read the article? Where it clearly says that this new study shows who should and should not get chemo? That’s pretty much the opposite of “one type fits all”.
2) You clearly are not familiar with any of the current immunotherapies, their risks, their side effects, their costs or their efficacy. I’m pretty sure it’s not a silver bullet if it costs $5 million. Or only works for one cancer. There is a lot of promise to cellular and non-cellular immunotherapies, but it’s not done and dusted.
3) Not even going to discuss the weed thing. Just not.
I suspect posts like these might get less comments, just because they’re more informative and less of a war. I hope that won’t stop you writing them, and I want to say thank you: this is a really important public service. Thanks for walking us through this.
Agreed. I’m really glad Orac wrote this. It’s grist for the grind when I comment elsewhere in forums where the science is less well understood by the commenters. I saw an article on this study in the Washington Post yesterday, and was hoping to see Orac blog about it this week.
Panacea:
Because many people can’t understand the complexity of how cancer development/ treatment, they are prime targets for woo-meisters. In fact, I try to assess the paucity of alt med charlatans’ comprehension by the nature of their explanations ( even considering that they may be simplifying it a bit for the sack of their followers). One of the concepts that can be compared amongst woo-meisters is how they explain why cancer happens at all: is it due to oxidative stress or infection by a fungus? I swear, someone says that.
Orac once provided a mind-boggling graphic that illustrated this complexity well. You’ll never see that at Natural News. Today they have an article about preventing breast cancer by eating avocado.
Yes, sadly this is so. I can’t tell you how many times I’ve had to try to explain to people just how hard it is to treat cancer. They think all cancers are the same, and they don’t understand the great strides we’ve made in cancer treatment in the last 30 years.
Even some of my colleagues don’t really understand it. I swear, I think I’m going to ask to teach the basics of cancer when I go back to teaching med surg next year. 🙁
I know I’ve commented before that curing cancer is like curing the common cold, for at least two reasons:
– Neither is actually one disease, but rather hundreds of different diseases that just have a commonality of symptoms, meaning a single ‘magic bullet’ isn’t possible;
– Both are really more about your body’s normal processes going out of control than about the specific invader, meaning that shutting it down without shutting down things in your body that you actually need to keep going requires some rather fine distinctions. (In the case of the common cold, my understanding is that pretty much all the symptoms are actually from your immune system reacting to the threat.)
I don’t think it’s too far out a prediction to say that we’re almost certain to cure the common cold before having any sort of general cure for cancer. It’s the easier problem.
I actually avoided media coverage of this because I was waiting for Orac to weigh in. I am glad I did.
One of Orac’s biggest fans ( Gary Null Show/ prn.fm, yesterday, 5-9 minutes in) reported on the study and added ( paraphrase):
in the 1970’s Samuel Epstein told** me the same- we wrote articles together. Many doctors tell me ** they can’t tell if the cancer or the chemo killed their patient. Medicine doesn’t acknowledge the tens of thousands who reversed cancer without chemo but used holistic modalities. SBM attributes reversal to chemo.
If you took a flu shot and didn’t get sick, SBM would attribute it to the shot. But suppose you ate a vegan diet, took vitamin C, stayed in the sun, reduced stress? SBM is feebleminded medicine.
Will he next critique oncology in his on-going series with Richard Gale? ( currently articles on Homeopathy, “Botanicals”, Chiropractic, Wikip– posted at prn)
I have the feeling that he couldn’t comprehend the diagramme/ graphs above.
** what is he turning into Trump?
I don’t see any NN response to the TAILORx study (they’re too busy railing against the GAY MAFIA and calling out “mass hallucinations” on the Left (while flogging their own delusions)).
But I suspect that if and when they get around to the report, it’ll be categorized as the MEDICAL MAFIA contradicting itself and revealing that millions of women were given TOXIC CHEMO unnecessarily when they could’ve been taking holistic supplements (like the ones offered in the NN store).
Alt med is always right, so it never needs to correct itself like the allopaths do.
@ Dangerous Bacon:
Right.
Mikey continues today interviewing Suzanne Humphries for InfoWars/ his own channel. Remember her tales about death threats a few months ago? WELL, it seems the Austin police/ FBI did not treat her appropriately and even possibly accused her of manufacturing the threats herself. Lots of bizarre stuff there in 44 minutes ( I skimmed). I am quite surprised the Mike doesn’t label the FBI as the Mafia or suchlike.
ACTUALLY, the Gay Mafia might be fun – like those guys who teach men how to dress better.
If I never see an article on buttons and double-breasted suits again, it will be too soon.
A tangential note: this study was funded in part by the breast cancer stamps from the post office. Which I’m very glad was publicized because I always wonder if all of the pink-washing crap does any good, and it looks like occasionally it does help.
Woo well-designed studies!
It was precisely this sort of irrational fear of chemotherapy that brought my late mother into the arms of alt-med and what ultimately killed her. When she eventually consented to see a real breast cancer specialist after it became clear even to her that her nostrum of choice wasn’t really doing shit, her doctor eventually found that her cancer was the sort that would have been responsive to hormonal therapy and she probably wouldn’t have needed to undergo chemo or radiation at all… had she decided to come to them soon enough. Alas, she had squandered years dithering about having a possible malignant tumour in her breast even looked at, and then after finally having surgery to remove it, she dithered with alt-med for more than a year, which gave the remnants of her cancer time to metastasize. The doctors gave her tamoxifen and several other similar drugs that they wished they could have given her a lot earlier, but it wasn’t enough to save her, not after the disease had progressed to the point it had.
To those of you who say: “what’s the harm?” when it comes to alt-med, here’s your answer. Alt-med can cause potentially fatal delays in effective treatment.
…alt-med stereotype of oncologists anxious to administer toxic chemotherapy
In completeness, the CAM criticism might be better offered as, “…alt-med stereotype of some/many oncologists anxious to administer expensive toxic chemotherapy”.
In my limited observation base, chemo + alternative lasted much longer than either chemo or alternative alone e.g. siblings, same cancer, combo lasted 3 times longer; or a CRC patient at the point of quitting after a year of second line chemo, sprints to another 3 years of chemo+alternative, in better physical condition; or combo lasted 4x longer than chemo alone curves with 99% – 100% wipeout.
In many cases, it seems clear, adding alternative nutraceuticals can enable people to handle more chemo longer with far better quality of life. Often these are documentable with unusual improvement in WBC, Hgb, cancer markers and other therapeutic indices. Sometimes even at higher chemo dosage.
It was a real pleasure to see such an elegant and appropriate application of a non-superiority test used to refine treatment options and encouraging that the evidence supports the avoidance of those treatments unlikely to meet the risk/benefit bar for specific patients. That’s rational patient-empowerment, proper informed consent, and shows that proper medicine is willing to undergo self-critique in pursuit of better outcomes. In contrast, it seems the wooniverse never, ever discards any treatment but only adds more.
The last time I was presented with a superficially similar study was a homeopathy trial that unsurprisingly showed that homeopathy was not superior to placebo and, in that particular case, also not superior to no treatment at all. Although the authors’ interpretation spun the results otherwise; they appeared not to understand that non-superiority is not evidence of efficacy. As we’ve been telling homeopaths that all along, it surprised me that they would have chosen to shoot themselves in the foot so effectively.
[…] for new cancer therapies. You might recall the flurry of news stories two weeks ago about the TAILORx trial, which clarified the use of the OncoType DX test to determine which patients with the most common […]
When will the clinically high risk patients be reported? They weren’t. 74% of patients were clinically low risk in this trial. What about the one third of patients under 50 years old? They had chemo benefit in RS 16-25. What about the RS 21-25 for all patients? They did too per the supplemental. How did the RS 26-30 do? Not reported. Unfortunately, there was no independent variable for comparison. It compared itself to itself. It is very dangerous to broadly claim that 85% of patients can forego chemo. It is simply not the case. Details/facts matter.