Opdivo - 1295068

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sezz
Opdivo - 1295068

I was reading the article by Dr West, How long should we continue immune checkpoint inhibitor therapy in patients who respond?

This was written in 2016 so I wondered if there is any more info now?

My partner has been on opdivo treatment for 3b nsclc for a little over a year. It’s worked well with all lung tumours stable. He has had lymph node increases, but the oncologist didn’t seem worried.

But lately he has been very tired, he gets increased shortness of breath (he has emphysema as well but the treatment definitely makes this worse). He also doesn’t want to eat much, although is maintaining his weight so this is not really a problem.

He’s just generally lacklustre and flat. He’s only skipped 2 treatments. One maybe 6 or 7 months ago, and then he skipped one 3 weeks ago. Then did another a week ago. He definitely picks up if he skips a treatment.

It’s difficult to know what to do. I tend to think/feel he should start skipping them now and again. If he says he’s discontinuing treatment he can’t get back on, but he can skip them without triggering any bureaucratic rules. But he has the attitude he’ll do the treatment if he’s up for it.

He’s not impressed with my women’s intuition as a good standard of evidence for skipping a few treatments, so I’ve been looking to see if there’s anything more concrete. I’ve asked our oncologist, but he always says, the drug is new, so nobody knows. Human bodies are all different, nobody knows.

Are there any studies/info about frequency of treatments, frequency of treatments etc? I have read somewhere that the treatment keeps working even after stopping it, which makes me think he could get away with skipping some.

onthemark
Hi sezz,

Hi sezz,

I'm glad to hear that your partner is getting a lasting response to Opdivo. Here is an OncLive talk amongst doctors from October 2017 discussing a recent Opdivo clinical trial and issues surrounding how long to give treatment and whether it is ok to skip treatment every now and then and maintain stability. It seems to be ok to skip a treatment every now and then according to the opinions of these doctors

'Duration of Immunotherapy for NSCLC'

https://www.onclive.com/peer-exchange/advanced-nonsquamous-nsclc/duratio...

sezz
Thanks for your help

Thanks for your help onthemark,

Do you know what it means when they say the half life of these immunotherapy drugs is 25 days? Google says half life means the duration of time the drug is active and the amount in your system has been reduced to half.

From the video "One point is that the half-life of these drugs—nivolumab, pembrolizumab, atezolizumab—is very long. It’s more than 25 days. And nivolumab is given, at the moment, each 2 weeks. So, for a very long period, it can be a bit difficult for the patient."

They give treatment every 14 days, and skipping one would mean no treatment for 28 days, only just past the active life of the drug. I wondered why they would use 14 day treatment and not treatments every 3 weeks?

JimC
Hi sezz,

Hi sezz,

It's terrific that your partner has had such a good response to Opdivo, but it's not at all unusual in such cases to skip treatments or increase the interval between treatments in order to minimize side effects.

The half-life of a drug is simply the amount of time it takes until only half of the drug remains in the body. I wouldn't put too much faith in the description of half-life as the time that the drug is effective. When new drugs are tested in trials, the eventual recommended dosage is set at the maximum tolerated dose, rather than the minimum effective dose. That's because the effective dose for each particular patient may differ, so the thought is that if you give everyone the maximum dose most patients can tolerate, you maximize the chance of a good response for all patients. The disadvantage of this approach is that some patients will get a dose higher than what they need, and suffer more side effects than necessary. With regard to half-life, if half of the standard dose remains in the body after 25 days, that amount may continue to be effective for some (if not many) patients.

As an example, the half-life of the standard 150 mg daily dose of Tarceva is 36.2 hours. At that point, 75 mg remains in the body, from the previous day's dose but another 150 mg dose has been added. Yet some patients who have difficulty tolerating that dose do quite well on as little as 25 mg/day. With that dose, at any given time there is much less than 75 mg of the drug in their body, yet it's still effective.

Your partner may want to discuss the possibility of either a dose reduction or an increase in the interval between treatments to, for example, 21 days. That might be an effective dose with fewer side effects.

JimC
Forum moderator

<p>I began visiting GRACE in July, 2008 when my wife Liz was diagnosed with lung cancer, and became a forum moderator in January, 2010. My beloved wife of 30 years passed away Nov. 4, 2011 after battling stage IV lung cancer for 3 years and 4 months</p>

onthemark
Hi Sezz,

Hi Sezz,

Just to add a short note to Jim's comments, your intuition is right. Because of the long half life one can move to longer times between the doses.


See the article "FDA Approves 4-Week Nivolumab Dosing Schedule"

https://www.onclive.com/web-exclusives/fda-approves-4week-nivolumab-dosi...

catdander
Hi sezz,

Hi sezz,

Without trying to explain something I don't entirely understand, the concentrations of drug in the body isn't a steady amount and opdivo is at it's highest levels just hours after or into infusion and fall off from there. Too there is an amount of drug that needs to accumulate in the body to be at a therapeutic level which can take weeks to achieve.

Most often new drugs in clinical trials are given for a specific purpose is first tested in humans to see how much of the drug a person can take. When a level is found that doesn't cause unsuitable side effects that's often the dosage set and used going forward. That's why we often find that if a person has unacceptable side effects a lower dose may be given (or less often 3 weeks instead of 2) causing fewer side effects and still efficacious. To this lay person this seems aggressive but I suppose for the pharma companies it means not spending time and money looking for the lowest effective dose then making less money because of less drug needed.

I'll ask Dr. Walko, our fab oncology pharmacist to comment.

It's better to skip a treatment than to stop treatment because of side effects. Most specialists easily agree to a skipped treatment when a person needs a break. They want their patients to live a enjoy life, that's the goal and if it means skipping a treatment because of a trip or just a break from feeling bad then they are normally all for it. We don't know yet why or how but some people appear to have efficacy from check point inhibitors many months after the drug has been discontinued. Perhaps if your partner hears this from the onc he would more likely be up for a break. I know I needed to begin discussions with my husband's onc in order for my husband to hear things. Oncologist are usually pretty in tuned with this type of dynamic and more than willing to work it.

I hope your partner does very well moving forward.
All best,
Janine

dr walko
Sezz,

Sezz,

I completely agree with what everyone has said and will just add one additional note about half-life. When we test drugs, we look at the concentrations of the drug in the body, which is commonly associated with the effects like killing off cancer cells. With several drugs, especially those that use the immune system for their effects (nivolumab/Opdivo and even steroids), we also have to consider the "biologic" half life and how long the effects last in the body. Since nivolumab acts to allow the body's immune system to recognize cancer cells and not get shut off by these cancer cells, the effects may last much longer than just the time the drug is actually found in the body. Nivolumab's biologic half life looks to be closer to 85 days so its effects last much longer than the every 2 or 4 week dosing.

This is just another reason that skipping a few treatments may not decrease efficacy like with some other drugs (like antibiotics or oral cancer drugs). Ultimately, these treatments are always a balance of efficacy and toxicity with the ultimate goal of killing cancer while maintaining quality of life. I completely agree with Janine's comment above.

Let me know if you have any additional questions!
Best wishes,
Dr. Walko

Christine M. Walko, PharmD, BCOP, FCCP
Personalized Medicine Specialist
Moffitt Cancer Center, Tampa, FL

sezz
Thank you everyone for your

Thank you everyone for your informative comments. It was very helpful and much appreciated.