how do I think critically about this immunotherapy drug for cancer?
June 23, 2019 9:19 PM   Subscribe

I started reading online about the immunotherapy cancer drug about to be given to my close family member. Now, instead of being hopeful for them, the list of deadly side effects has me terrified. Metafilter, can you help me think about the risk/benefit appropriately here? Details inside.

Immediate family member in question is about to undergo immunotherapy for stg 3B lung cancer. Drug name is pembrolizumab (KEYTRUDA). If they have one of the side effects, it seems like things could go very wrong, very fast. Versus, if no immunotherapy is given, they have a shot at 12-15 months life expectancy.

That's the part that is so scary. I feel like the risk might not have been properly explained. But I'm not even remotely qualified to assess any of this! Certainly I'm not a doctor. What I am is emotionally and cognitively drained, confused, and hoping someone here might have some insight into how to think about what is about to happen appropriately.

Whereas, right now, I just want to stop them. "Don't do it!" I keep wanting to scream, you might get {insert deadly side effect}!!

That can't be the helpful approach. What is?

Any thoughts or suggestions are super welcome.

Some other details, in case:
This is first, no chemo or radiation yet.
They are late 70s and otherwise healthy.
At a really great top cancer hospital in US and oncologists were positive about this and downplayed the risk.
I am a worrier by nature and seem to be the only one in the family freaking out (but also the only one asking questions and trying to learn more about the drug, it's new-ish. 2017, I think, FDA approved).
posted by OlivesAndTurkishCoffee to Health & Fitness (14 answers total) 1 user marked this as a favorite
Have you been at all their doctors appointments, and getting all the explanations that the patient has been getting? Or are you working on second hand information?

Are you familiar with the side effects of other medications, or is this the first time you've tried reading up on treatment options for something? Are you able to evaluate the probability of side effects?

Is the 12-15 months life expectancy you mention actually their personal estimate? It sounds very close to the median life expectancy of all stage 3b patients, and if that's what you're talking about then you are using as a reference then you probably need to adjust your expectations because a 70+ year old patient, even otherwise healthy, should not be looking at median outcomes for the whole population.
posted by the agents of KAOS at 10:27 PM on June 23, 2019 [8 favorites]

I developed an aggressive form of Acute Myeloid Leukaemia about this time last year. The chemo was too much for my damaged bone marrow, so I was offered a Bone Marrow Transplant which I had in December. I am now on a trial called MicroLen for people at high risk of relapse.

The list of potential side effects for pretty much all the drugs I've had to take are terrifying. The trial drug in particular, Lenalidomide, has two full pages of terrible things that may happen. This is the nature of those documents; they list every possible thing that might go wrong. I've had no significant side effects.

At various points during the process, I made the only decisions that made any sense to me, which were to take the advice of the experts who were looking after me. Everything about the way they operate was and is confidence inspiring. If your family member is at a top cancer hospital then they're likely being cared for by highly qualified and experienced people who are very clever and have worked extremely hard to be good at what they do.

Unless you have legitimate doubts about their competency, I suggest you take their advice.
posted by mewsic at 12:06 AM on June 24, 2019 [11 favorites]

All that counts is the judgement of your family member: Do they want to take a risk of dying earlier because of the drug, or living longer, if it works? When we make calculations like this they are usually not so much dependent on the mathematical probabilities inherent in the choice, but on our own stamina, and our own balance of pessimism and optimism. Someone who doesn't want to suffer and figures it's all hopeless anyway will refuse minor chemo that has a 95% chance of eradicating the cancer. Someone who is filled with the blazing hope of healthy life may choose a 5% chance of eradicating cancer and a hideous regime of treatment, over palliative care that would leave them functional, not be traumatic, but let them die after twenty years of pill taking. It's really all up to the person who has to go through the treatment. The only thing you need to know is if they want to take it, or if they would rather not.

Your feeling of terror is early stage grief. It is just, it is appropriate, it is a measure of your love for this person. It's you displacing the devastation that this beloved person is definitely going to die and definitely going to leave you, (unless you exit first) on their treatment choices. It is you preparing to do anything at all necessary to protect them. But of course, you have to decide if speaking up, if researching, if quizzing their doctors closely, is something that can actually help. You want to have that power, and you are the very valuable family member asking questions and being the eyes to protect them from mistakes, but this leaves you vulnerable to suffering over these questions.

I'm so sorry. I can't help you choose. I can just tell you that that terror you feel is because you are loving person, and are trying to save someone you love.
posted by Jane the Brown at 3:44 AM on June 24, 2019 [16 favorites]

I am a cancer patient taking a drug with terrifying possible side effects (lenalidomide, in fact, mentioned by mewsic). So far my side effects have been pretty minor, but that could change. This drug seems worth the risk to me, but I have also refused a drug that most patients with my cancer take, and I’ve refused a stem cell transplant, which is still considered the standard of care despite the fact that it can kill you and has never been shown to increase overall survival for my cancer. I think that oncologists in general really downplay risks of treatment, so I am with you there.

That said, there are just differences in the way people view medical treatment. Jerome Groopman’s book Your Medical Mind really helped me understand that people have different ways of making decisions, and I highly recommend it. Some people really do want to do whatever medical science has to offer despite the risks, and that’s ok. Some people think you should do whatever your oncologist thinks is best (I don’t). I see both attitudes all the time in my online support group at

Speaking of, I highly suggest you go there and join the community for lung cancer. You can then start a thread about that specific drug and hear from patients who’ve actually taken it. I think that will help you a lot with your fears. We hear a lot from people who aren’t themselves the patient, so you would be welcome there. You’ll be able to get way more specific info than you can here.

Best wishes to you and your relative.
posted by FencingGal at 3:59 AM on June 24, 2019 [4 favorites]

Oh, I’ve been where you are. ( Literally-Dad was just declared NED from Stage III b lung cancer earlier this month, two and a half years after diagnosis. Keytruda was pretty much his last resort choice after the side effects from the radiation were too brutal and the ca grew in spite of chemo. I may be biased) Thinking critically when your loved one has been diagnosed with this is HARD. You must have so much going on right now. And as a fellow worrier, yikes, I can relate to the reaction to perusing those lists. There was definitely part of me going “ you’re going to get all of these and I’ll lose you even sooner.”
Please keep in mind that side effects lists of anything they’ll use to treat the ca will have a lot of terrifying conditions; that doesn’t mean it will happen to them. If they choose to take this route, don’t be afraid to be in contact with their care team. Ask questions; what are the most common side effects, what are the ones that ring alarm bells? If you see your family member exhibiting a sign or symptom after treatment, don’t be afraid to call and ask about it. Sometimes they told us to watch and wait, sometimes they told us to come in.They’ll be used to discussing this w patients and family.
Definitely sign up for online or in person support. It such a huge help to see people share what they’re going through. Big hugs to you and your family.
posted by jacy at 5:50 AM on June 24, 2019 [1 favorite]

In 2015 I had a year of chemotherapy and newer targeted therapy drugs for breast cancer. The side effects can include neuropathy (permanent numbness and pain in the extremities) and congestive heart failure. I didn't have those or any of the serious listed potential side effects. Most people do not.

Your family member's doctors are prescribing the drug because the benefit vastly outweighs the risk. They're aware of the potential side effects, and they know what they're doing. You have to trust them. And, maybe more importantly, you have to keep your mouth shut about any concerns you have. This is not your life. The patient does not need to be stressed by hearing anybody else's opinions about their treatment. I know it's hard. But it's so, so important for you to mind your own business right now. I promise that you don't have more information about this than their oncologists do.

For what it's worth, also - nine years ago my father had melanoma in his brain and liver that killed him in two months. Jimmy Carter had the same diagnosis, and is alive and healthy four years later. Keytruda is a huge game changer. They prescribe it for a reason.
posted by something something at 6:34 AM on June 24, 2019 [6 favorites]

Speaking as a former medical writer—they have to list basically any effect that happened in any of the trials, if it could reasonably be ascribed to the drug. That’s true if even one person experienced that side effect. So while the list sounds scary, keep in mind that they have to list everything, and if those serious side effects happened to many or most people in the clinical trials, the drug likely wouldn’t have been approved.

Speaking as the daughter of a former Keytruda patient—my dad was in one of those clinical trials, for throat cancer that spread to his lungs. He’s a former Keytruda patient because it worked amazingly well. The cancer is in remission, he gets scans every 3-6 months to ensure it hasn’t come back, and otherwise he’s living a great life, 5 years out from his diagnosis. He’ll be 70 soon. He had no noticeable side effects from Keytruda. Obviously this is anecdotal and just one person’s story, but perhaps it can bring you some hope or comfort. I wish the best for you and your relative.
posted by Illuminated Clocks at 8:34 AM on June 24, 2019 [2 favorites]

Disclaimer: am involved professionally on cancer diagnostics, and am familiar with the current boom in individualized therapies (that use diagnostic tests to personalized treatment).

Pembro and other immunotherapies are intriguing as a certain population of patients that are PD-L1-positive (the main immunotherapy diagnostic marker, there are others) will have 'durable response'; i.e. they survive for a long time.

Here's a link that indicates for NSCLC, it would be up to a 25% long-term survival rate. For melanoma, what was previously not a lot of optimism, with these immunotherapies also see 20%-30% durable response (i.e. patients that basically go into remission). Jimmy Carter is a prime example of this - he's one of the lucky ones, and still alive today because of it.

Thus in spite of the risks of side-effects, it is worth a try - your loved one may be one of the lucky ones. The search is on for finding out what other markers predict immunotherapy response, but after years of hard work additional markers (such as Tumor Mutational Burden or TMB, or Microsatellite Instability or MSI, other gene expression markers) have yet to have strong predictive power.
posted by scooterdog at 9:30 AM on June 24, 2019 [2 favorites]

That can't be the helpful approach. What is?

"I support your choices. Let me know if you want to talk about it"

My mom died from cancer a few years ago and she said that one of the hardest things for her was having a terminal disease and having people give her advice about her course of treatment after she'd decided what to do. She was also an anxious person and a little afraid of making a fatal mistake so people showing up with "OMG don't take that medicine!!" might have caused her to seriously consider not taking it. Presume your loved one's doctors are working with her best interests at heart and what you see as "downplaying the risks" may just be how oncologists deal with this sort of thing. Possibility vs probability vs. long term gains is their jobs.

Presume that you are feeling sad and a little out of control because you have a loved one with a terminal disease and your feelings are completely understandable but need to be kept to yourself or talked out with someone who is not your loved one with cancer.

You've probably seen it but the "comfort in, dump out" technique is helpful here.
posted by jessamyn at 12:41 PM on June 24, 2019 [6 favorites]

Toxicologist here, who also has an autoimmune disorder and has had to take antibody-based drugs with the potential for terrifying side effects (like pembrolizumab). Adverse effects are a given, but the scary black box warning-type that catch your eye are relatively rare. Something I do with friends who ask similar questions is to sit down with them and read through the full package insert. We highlight things that give them pause. We do a little due diligence with the literature on the frequency and severity of those adverse effects. Then, they can go and have a pretty put-together list of their thoughts, questions, etc. for their next doctor visit. Do you think something like that's in your wheelhouse? If so, maybe offer your ear and some time to jot notes so they can transform those nebulous anxieties into detailed, specific questions for their medical team.
posted by late afternoon dreaming hotel at 4:40 PM on June 24, 2019 [2 favorites]

In the pharma industry, but have not worked for Merck or on Keytruda.

It might help to know the reputation of Keytruda. It is a PD1 inhibitor, first in a new class of drugs that has as much buzz and excitement as I've ever heard about anything. Last years' Nobel Prize went to (some of) the inventors of this approach; the results in patients have been so promising researchers are looking everywhere for similar approaches to treatment. There are over 1000 trials registered at This also means its been given to a large number of people, both in clinical trials and now since it hit the market.

The page you linked to has the list of side effect but not their frequency. If you want you can google for the package insert for Keytruda, which has the frequency as well. There's a lot there in possible issues, but the severe events are very rare. When they talk about adverse events Grade 3/4 are the serious ones, with Grade 4 being life threatening and probably the only ones I'd really worry about if I had a terminal diagnosis. (And grade 5, which is actual death.)

Everyone's different but after going through the insert, if I had the prognosis you describe, my only worry would be dying from cancer, not medication effects. And this isn't true of me for all types of cancer medications--there are some where the intellectual risk/benefit still would lead me to take the drug but I would be freaking out.
posted by mark k at 6:41 PM on June 24, 2019 [2 favorites]

My mom entered a stage 1 trial for Opdivo (Nivolumab) when she was first diagnosed with stage 4 nsclc about 6 years ago. As an early stage trial, they were still experimenting with dosage and combinations. (In fact, she received a combination of nivolumab and ipilimubab.) With a stage 4 diagnosis, her prognosis was very poor (6-12 months), and so we as a family decided to take a risk on the trial, given that there weren't many options available, and possible upsides of immunotherapy seemed worth exploring.

You might consider getting a second opinion, as this was helpful to us, particularly in understanding the risks and what we had to potentially gain vs. lose. It was explained to us that we could always pursue traditional chemo/radiation later and that side effects would be tracked closely. There was quite a lot of excitement at the research hospital for these trials, and a waiting list of people hoping to have a chance to qualify, so that certainly added to the sense of weighing possible benefit over risk.

My mom only had two infusions before she started to experience kidney failure (a bad side effect), and had to be taken out of the trial. I mention this for a couple of reasons. First, the kidneys eventually mostly recovered (over about 6 months), though nobody knew at the time whether this would happen and it was later determined that it was the ipilimubab that caused the toxicity. Presumably, later trials reduced or eliminated that component. That was a bad outcome. However, along with that side effect, even after just two infusions, she experienced a significant reduction in tumor size, and went on to have more than a year of no progression of her cancer, even with no further infusions of the drug. Secondly, after pursuing more traditional chemo off and on for the following couple of years, she came back to the nivolumab (now FDA-approved as Opdivo), and it helped slow the progression of the cancer for a couple more years. (My mom passed away earlier this year, having the gift of a largely healthy and active extra 5 years beyond her original prognosis.)

I guess what I'm saying is that there is both benefit and risk, and while there is no guarantee that your family member will get the only the benefit and none of the risk, it's possible that you can have both and still have a good outcome. And, they can later try other treatment approaches if side effects of Keytruda are unmanageable. My understanding with immunotherapy is that for the people it works for, it *really* works, and for those it doesn't, it doesn't, and it doesn't take too long to figure out which group you are in.

I don't mean to try to convince you that immunotherapy is absolutely the right choice, but I hope this gives you a different way think about the risks and benefits. There is no right or wrong answer here. It's more what you and your family think you can accept risk-wise, and how you think you might look back on this gamble later. I agree with Jessamyn that it's probably not good to insert yourself into this kind of decision-making if your opinion has not been explicitly requested, but assuming it has, the best thing you can do is help the person explore the possible outcomes and work with their doctors to choose a line of treatment that they feel comfortable with.
posted by amusebuche at 8:33 PM on June 24, 2019 [3 favorites]

You might try looking at the side effects for something you wouldn't have any qualms about taking, like ibuprofen or cetirizine. The package inserts make everything look lethal.

Keytruda is a relatively novel drug and it's not as well understood as the older medications, but for the majority of patients who are taking it, the potential benefits seem to outweigh the costs. I have a dear relative who also has stage IIIB non small cell lung cancer and who took Keytruda for a while. He actually did develop pneumonitis and had to stop taking it, but he actually felt okay during all that time--it was detected early on one of his frequent CT scans. This is one of the reasons they do blood work and imaging so frequently.
posted by The Elusive Architeuthis at 9:47 PM on June 24, 2019 [2 favorites]

You can all sleep well tonight, wise hive mind, knowing you really HUGELY helped someone out.
Thank you. And thank you again with hugs on top.
posted by OlivesAndTurkishCoffee at 8:32 PM on June 26, 2019 [2 favorites]

« Older Enable my cheese toasties please   |   Do you exist? Newer »

You are not logged in, either login or create an account to post comments