I have no medical experience, but I've read many books on the subject of cancer, the history of chemo, and how doctors "test" new drugs. Some of their test protocols do not make sense to me. In one instance, an immunotherapy drug was working somewhat, and the testing protocol then required them to increase the strength by some ridiculous amount....like 10x. The patient, of course, got worse. So they said the drug wasn't working...at all!! I don't understand how they decide these protocols. The protocols fly in the face of common sense!
I think the comments reflect more hope than common sense. These were 3 extremely I'll patients with rapidly progressing cancer. Traditional treatments that had worked for them in the past were no longer effective. People generally join trials as a last hope effort. I'm very sorry for their suffering and that of their families. I wish my mother had the chance to make that same choice.
Science isn't often perfect in its infancy.
20
Before any medical treatment is trialed on humans, it undergoes extensive testing in animals, then healthy volunteers, then small groups of those with the target disease, then large groups of those with the target disease. While we do everything we can to prevent complications from arising, unforeseen complications arise and sometimes people get hurt. We work to limit complications from arising by screening who is entered into a trial and ultimately who receives the medication. The "right to try" ideas puts vulnerable individuals at risk of putting themselves into trials that could help, but could also have a greater risk of causing harm as the patient could lack the profile that makes the treatment suitable as designed.
13
This is exactly why this "right to try" law is a BAD idea. Ae should not be skipping the science, ,especially if there is a chance that the new treatment will make things worse. It also throws open the doors for all kinds of crackpot treatments from con artists.
9
Those evil drug companies---trying to cure cancer and make a profit at the same time !
We need government at all levels to develop and test drugs and provide them to everyone for free.
2
Getting funding from this administration? Good luck with that!! EPA and FDA are under seize. NIH is cash starved. As progress in science, this administration thinks evolution does not exist and global warming is a hoax.
2
New oncology drugs, especially in IO, are tested in indications for which they did not receive initial approval. That is also the case here. A similar Mab, Keytruda was initially approved for melanoma and now it appears to work in NSCLC and other indications for example. It may sound callous but this is how progress is made. And we are just really beginning to understand immuno oncology so there will be failures in clinical trials.
14
Anytime you take a new drug, even one that has been through preliminary trials, you are signing on to be a guinea pig whether you know it or not. It can take years to identify all of the side effects and risks of a drug--remember Celebrex?
That said, people whose only option is death should be allowed to try such treatments if they wish, as long as they are capable of understanding that the drug is still in the trial stage and might worsen their condition, have unpleasant side effects or do nothing.
7
I thought modern medicine was supposed to be moving toward not making big decisions based on very small data sets...N=3?
6
This borders on malpractice. First of all the therapy is not approved for this type of cancer. Second, this therapy directly effects the t-cells in a way that could hasten the disease. The doctor should have known better.
3
Well, the article said that scientists don't understand why sometimes the disease is aggressive and sometimes it is indolent. If this drug caused indolent cases to turn aggressive, that's a clue that something very like the action of this drug may be occurring naturally in the bodies of patients with the aggressive form and if scientists can figure out what it is, there's a potential target to create a drug to block it. Don't let information arising out of this tragedy go to waste.
25
They're called guinea pigs for a reason. I would NEVER do this, unless I had at least a 90 Percent chance of Death within a year, AND my Family was well paid. Seriously. Beware.
2
For the patients, the drug was a big failure. For science, however, this is an example of a good failure. Why? The failure illuminates the function of the drug. Much of the time, scientists test out drugs and nothing happens at all. Complete failure. But this drug had a big effect; it did the exact opposite of what it was supposed to do.
This kind of failure gives scientists a way forward. Because there is an effect, they have an action that they can study and try to manipulate.
A drug that does something, even the wrong thing, provides a view into the mechanisms of a disease. It’s like having a key that fits into a lock just well enough to jam. You at least know that you are close to having a key that is the right shape.
I hope the scientists can follow up with all the involved patients and get enough data to keep their research moving ahead.
43
My son-in-laws father in New Zealand has serious cancer, including brain cancer. The doctors used immune-therapy and the cancer tumors are gone or greatly reduced.
If our BIG pharma cared more about cures than making money WE would have effective treatments. Why don't we have access to international treatments that work?
What a backwards situation. WE THE PEOPLE must DEMAND that BIG money be purged from OUR medical establishment at every level. WE pay for the research and they get the disgraceful profits. It MUST end. NOW.
12
Government and public funded labs (like Universities) can and do own patents on various drugs. But they are more likely to own patents on drug mechanism than on specific drugs. For instance, the mechanism that makes Prozac work was discovered in a public lab, but this was not the drug itself. Lily licensed the mechanism and then created Prozac from that. Lily of course got rich off of it.
From the period 1990-2007, about 10% of newly released drugs were created in this way - the work initiated in a public funded lab, but the actual drug was created, tested, and brought to market by Pharma. The remainder (about 90%) of newly released drugs come from private research, not public. Over the last 10 years, the percentage of drugs that resulted from public funded research has climbed to about 20%.
So, Pharma is making money off public research, but (a) they pay for it through licensing, and (b) it is not the majority of new drugs.
6
Where is your evidence that "big pharma" cares more about money than cures? Without drugs that actually work, they don't make money.
1
Too bad you have no idea how medical studies are actually instigated and done, nor how physicians decide who to treat and with what.
11
Every outcome, whether good or bad is data, perhaps gleaned at the cost of someone's life, and is precious, even though it can be very difficult to evaluate and interpret. The big question is why a treatment works in some cases and not in others. Thus every case should be kept and followed up, even if costly. There are nasty aspects to these trials, particularly that they are not really intended to cure patients (except in a general long-term sense), but to understand the science and to test particular products of the company paying the bills. Losing track of the patient if the treatment doesn't work is profoundly wrong.
29
You won't find a better place to understand the problems posed in putting cancer and immunotherapy together than in Barbara Ehrenreich's book, "Natural Causes." Her Chapter 7 is a good place to start: The War between conflict and harmony" in our body's tissues. "Cancer came to focus on DNA mutations, downplaying cellular dynamics of the immune system in favor or an obsession with antibodies." Ehrenreich's point is that Deadly combat among cells is part of how the body, especially the human body conducts its normal business. She suggests we are more confederations, or temporary alliances, of microscopic creatures. She wrote a phD thesis in Biology, and yet she writes for all of us.
6
I read with interest your article about this immunotherapy drug. But I was quite surprised to see you didn’t name the company that manufactures Opdivo. Why was Bristol-Myers Squibb not mentioned anywhere in this article? I would think that would be very important fact to include. Can it be that their public relations department did an excellent job of “convincing” you that this was an unnecessary detail for readers?
9
What could a reader conclude by knowing that Briston-Myers Squibb wast the drug manufacturer? Was that important to the report?
4
They are still running that pathetic Opdivo commercial on TV! Saw it yesterday! Thought right away, when I heard the side effects, they sounded a lot worse than the actual malady! What can be worse than death, from a drug that supposedly is helpful?! How was this approved by the FDA?! Most importantly, why are they allowing these commercials on TV?! And the ones for Jardiance?! Give me a break! Are the inmates running the asylum, when it comes to marketing drugs?! Where are our legislators?! This is an example of the free market gone nuts!!!
23
@Counter Measures
The FDA does not approve TV commercials. Ever hear of "freedom of speech"? Healing "spring water" is also advertised on TV, and it's free. Drink it and your addiction will be cured. FDA approval is not required, and the audience to which the "spring water" appeals doesn't care.
That is incorrect. The FDA does review all direct to patient advertising. It is not a freedom pf speech issue.
3
Read the article again. It adversely affected three patients with a very specific type of lymphoma. That does not mean that it is failing every person with lymphoma.
12
I just got done reading Barbara Eirenreich's latest book 'Natural Causes'. I highly recommend reading this. Guess what, work out daily, eat strict diets, do all of the medical tests, rely on fads and latest health trends and die anyway. 155 million of us do it every year, (2.4 million in the US).
9
Am I missing something? This article does not mention Bristol-Myers Squibb even once, as the drug manufacturer of nivolumab. Totally irrelevant?
7
While we all empathize, and some of us sympathize, with the cancer patient, immunotherapy is so expensive that it will never be ecconomically viable. How can we afford to spend a $100,000, or more, a year per patient?
11
@Jay David
This is science. First, find out what works, then worry about the price.
2
Are you missing a zero? Because $100K is very little when it comes to cancer treatment. That is a couple rounds of chemo (or perhaps just one in some instances).
3
A friend who died last year from a rare form of skin cancer was allowed by the VA to try a drug a research arm of a university was developing. It did nothing to the cancer and it left him with permanent pain in his feet. However, he never said he regretted trying.
16
This article shows one of the problematic issues with the Right to Try" law. A patient with this disease might have requested this drug for "compassionate use' and suffered greatly. Medications need to be proven to be safe and effective before being given as treatments.
18
The only was to prove safety and efficacy is with trials in humans. Patients enrolled in the trial with this form of cancer would have experienced this side-effect. In the end it is the same result.
7
The issue I see with "right to try" is that the patients aren't consistent with other patients who might be in a trial, so their experiences wouldn't contribute to the body of medical knowledge and practice that results in progress against these diseases.
I'm not against last ditch efforts, even if they might make the disease worse, but they need to be able to share them with others.
In that regard this study was a success in that it seems to have answered questions about this drug. It doesn't work for people with this rare type of cancer.
6
Articles like this should appear regularly. Not to dishearten those who are buoyed by thoughts of cures but as a counterpoint to the known difficulty of getting results of negative trials published, "medical breakthrough" headlines and the constant din of drug company advertising for expensive but often marginally effective drugs.
Like vitamin E for heart disease and secretin to cure autism or the wide spread use of estrogens for menopause, some things that seemed like a good idea at the time do not hold up under careful scrutiny.
When your eyes glaze over at talk of the federal budget remember funds are needed to support publicly ( not drug company ) funded medical trials with robust follow up and required reporting of ALL results to continue to improve the health of all of us.
39
While it is important to report all results from clinical trials, remember they are only powered for the primary efficacy endpoint. Other endpoints and subgroup analyses have to be interpreted very carefully. Importantly, any analysis that is not prespecified should be only be considered exploratory.
8
Unfortunately, we will almost certainly see a much larger number of patients hurt due to such unexpected outcomes.
While it is little or no comfort to the patients who suffered through this, the fact that it happened during a controlled clinical trial with strict performance and safety monitoring at least limited the number of those who were hurt by an unexpected (negative) outcome. In a case like this, the current move by the Trump administration and the Republican congress to facilitate broad "early access" to medications that are still in development would have meant that many more patients would have been treated and hurt. It is unfortunately almost certain that future cases will bear this out. Premature wide use of treatments that have yet to prove their efficacy and safety in large, controlled and well-supervised clinical trials (so-called phase 3 studies) might well save some lives, but also greatly increases the risk of having hundreds or thousands of patients being exposed to such serious, unexpected effects. The situation described here is a case in point: There were good reasons to believe that it "should have worked", but it didn't, and made it even worse.
7
As a former oncology research nurse I find it troubling and alarming that Dr. Janakiram and Dr. Brammer in essence state they did not know how their clinical trial subjects are doing now because they went back home for treatment?
If I were a Principal Investigator I would want to know how they are doing. Where is the Institutional Review Board role in this matter? Clinical trials matter, and if this is how study subjects are treated and discarded, well, maybe fewer people will consider a trial.
87
They don't know how those patients are faring...really? Have Dr. Janakiram and Dr. Brammer not heard of the telephone?
61
For most clinical studies, after a subject discontinues, the sponsor is required to follow any ongoing serious adverse event until it resolves. Survival would also likely be tracked.
23
I highly doubt any study subjects were "discarded" in this situation as you suggest. Virtually all clinical research studies are designed to follow subjects for a set period of time after completion of their active participation or treatment on a study. However once they are officially "off study" and no longer in the follow-up window, there is no obligation on the part of the patient to continue submitting to follow-up investigations, or the study investigators to continue following the patient's outcomes. No research subject is followed indefinitely, and all research subjects have the ability at any time to withdraw their participation or opt out of continued follow-up. If research studies required subjects provide their medical records and be subject to clinical monitoring by investigators for the rest of their lives, it's unlikely many people would willingly choose to participate in research.
7
What a humbling situation, harming patients (with drugs of unproven efficacy) while trying to help them. And yet, without 'trials' we may not be able to advance as fast as desired to help others. Personalized attention and care is coming, exciting times while unsettling to any individual outcome...for now.
1
I felt extreme disappointment after reading this article because the other stories I read previous which are referenced in the "Related Coverage" section wrote of such hope, optimism and promise for cancer patients.
I think Dr. Brammer's statement “In science, when you administer a drug, you expect one outcome, but until you actually do it you don’t know what the outcome is going to be,” is key and should always be remembered and stressed to patients when ANY treatment is contemplated or administered.
Science has never been a "one size fits all" proposition. When hope and optimism is delivered to a patient in the form of medicine and treatment, so should caution and an honest conversation of potential negatives or set backs. A cancer patient should be made aware of any and all potential risks.
Thank you NYT for shedding some balance on this ever evolving story and various cancer drug protocols.
20
..."When hope and optimism is delivered to a patient in the form of medicine and treatment, so should caution and an honest conversation of potential negatives or set backs."... This is all the more important now that regulations for "last ditch" treatments have been loosened. Even if outcomes and setbacks are unknowable, patients need to know.
7
@Susan
Agreed completely.
Alexander Graham Bell reportedly stated that “When one door closes, another opens”. It makes sense that pharmacologic approaches, such as checkpoint inhibition with checkpoint inhibitors, such as the one used in this study, that activate T-cells will worsen the clinical condition of patients with T-cell lymphomas. The finding that checkpoint inhibition that increase T-cell-mediated autoimmunity do indeed worsen the clinical condition of patients with T-cell lymphomas, in combination with the increased risk for lymphomas in individuals with celiac disease, which is a condition with an overactive autoimmune system, raises the possibility that checkpoint activation with checkpoint activators that decrease T-cell mediated autoimmunity may be an effective T-cell lymphoma treatment approach.
9
I don't understand... How can the researchers not keep track of the patients even though they were taken off the drug, especially since the drug seemed to have a dramatic, if adverse, affect?
54
Because they are not paid to do do, by the biotech companies developing the drugs. Greed abounds in this industry, and the amount of money involved (whether in the form of personal wealth, or the promise to fund one’s research program) can blind even an honorable physician researcher.
4
Researchers likely tried to track the patient since this is part of most research protocols. However, the patient has to voluntarily submit follow-up answers - they cannot be compelled to do so. Patients may be too sick or may have other reasons for not following up. Privacy laws prevent the researchers from contacting the hometown physicians or family.
25
If the patient leaves the trial, it’s one metric on the outcomes so they’re not included in the final numbers. It’s not greed. It’s to maintain accuracy about patients who completed the trial. And the data is often evaluated by trial investigators and independent review councils. The objective is helping the greater good, finding out if the drug works, not how patient 348 is doing now.
7