Mixed Results from Treatment

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sch1979
Mixed Results from Treatment

Has anyone had mixed results from chemo/immunotherapy?  My uncle was diagnosed with stage iv nsclc (exon 20 mutation).  It has spread to the bones, lymph nodes and adrenal glands.  He did 6 rounds of chemo with immunotherapy (alimta/keytruda/carbo) and then continued with keytruda/alimta.  We just received his first PET and brain MRI results since his initial diagnosis and while some of the cancer shrunk, some grew and there are new lesions not seen in April. The oncologist said not to be alarmed and wants to continue immunotherapy and re-test in three months.  Is that a typical response/course of treatment for mixed results from chemo? I'm very concerned about the new growth.  

 

JanineT Forum M...
Hi sch1979, Welcome to our

Hi sch1979, 

Welcome to our new site.  I'm sorry to hear about your uncle.  It's not unusual for there to be mixed results to treatment.  However, if it's been 8 months since his last scans at diagnoses it would be difficult to say what happened when.  It could be that there were already new mets on the horizon (already growing but not large enough to pick up on scans) when first diagnosed.  It's typical to follow someone's treatment with CT scans every 3 months or so which gives you a better idea of what's happening during what treatment.  Except in special situations PETs aren't really going to tell his onc anything a CT can't and the CT is much cheaper.  

If your uncle isn't suffering worsening symptoms then there would be no reason not to continue with keytruda however the overwhelming majority of people with an egfr mutation don't respond to immunotherapy alone which is why most would continue with a combo with alimta and immunotherapy (as long as the side effects are manageable).  There are many promising treatments in trials for those with a mutation in exon 20 all over the world.  Below is a link to a group specifically for connecting and sharing information about exon 20 both egfr and her2 (both of which often respond to the same treatments).  A Grace member, scohn is very much tuned into what's happening in this area for his wife has a mutation in exon20.  If he's available he is very knowledgeable and responsive so you can send him a message from your dashboard.  

http://www.exon20group.org/

I hope your uncle does well.

All best,

Janine

scohn
Some Thoughts

Hi sch1979.

I am so sorry to hear about your uncle's diagnosis.  As noted above, my wife has NSCLC with a HER2 mutation, which is very similar to the Exon 20 mutation in EGFR (in a different but related protein). I agree with Janine that we found the Exon 20 Group very helpful -  they have a lot of information about both current and developing treatments for Exon 20 mutations.  They may have some suggestions on things to talk about with your oncologist.

As for mixed results in chemo, we have definitely had that.  In two cases a line of treatment did great in the lung and nothing for the liver tumors.  In most cases, however, the line of treatment seemed effective or not on all the tumors, although with different degrees (some worked better on liver, some better on lung).  My wife has some cancer in her hip which seems to be a good indicator for her - for the treatments that work the pain goes away quickly, and if the pain there comes back usually the treatment is not working overall.  For my wife the carbo/alimta worked great, while the alimta alone, as well as Opdivo, not at all.  She has been in two clinical trials - one which worked for about 18 months, and one which had a mixed result.  The more standard chemotherapies, carbo, Gemzar, and Abraxane (a type of taxol) have been the ones that have actually worked the best overall.

Please let me know if there are any other questions I can answer for you, and I wish you and all your family a New Year full of peace and health!

 

-scohn

Wife, non-smoker, dx 4/24/15 adeno NSCLC stage IV. HER2 Exon 20. 6x Carbo/Alimta; effect. 9/15 Alimta maint; ineffect. 11/15 - Opdivo; ineffect. 4/16 - ptK7 trial; effective 1.5 yr. 9/17 Gemzar; effective 16 mo. 8/18 -TAK788 Trial. 10/18 start Abraxane. 7/19 start Kadcyla.

JanineT Forum M...
I wonder if there's a

I wonder if there's a relationship between exon 20 and inefficacy of alimta. 

scohn
Interesting Question

Hi Janine.

 

I think this is exactly the type of question they will (hopefully) be able to answer as they correlate more clinical results with patients' genetic profiles.  For example I did find one study (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869778/) that showed Alimta did not work as well for HER2 as it did for some other mutations.

Wife, non-smoker, dx 4/24/15 adeno NSCLC stage IV. HER2 Exon 20. 6x Carbo/Alimta; effect. 9/15 Alimta maint; ineffect. 11/15 - Opdivo; ineffect. 4/16 - ptK7 trial; effective 1.5 yr. 9/17 Gemzar; effective 16 mo. 8/18 -TAK788 Trial. 10/18 start Abraxane. 7/19 start Kadcyla.

Jim C Forum Mod...
Jim C Forum Moderator's picture
Interesting question

scohn,

I agree, and I think that when a larger number of patients receive broad-spectrum genetic testing we may really see rapid improvements in matching treatments to a particular patient's genetic profile. 

Jim C Forum Moderator 

 

sch1979
Hello all.  I am sorry that I

Hello all.  I am sorry that I am just now responding.  For some reason, I thought I would receive an email if someone responded to my post, and so I thought noone had responded.  Thank you to all who responded.  I really appreciate it.

I wanted to give you all an update and ask for some advice as well.  As I posted, in Dec. we got mixed results to the treatment.  (Diagnosis was in April 2018, treatment was keytruda/alimta/carbo.  First scan showed it was working very well.  Dec. scan showed mixed results.) The oncologist did not believe that the mixed results showed that the treatment was not working.  There was some growth, but also a lot of reduced activity, so we continued on alimta/keytruda maintenance.  Unfortunately, the March scan showed the disease progressing and the oncologist now agrees the treatment is no longer working.  She is recommending taxol or a clinical trial.  We have an appt at NYU on monday to see if we can get into the poziotinib trial.  I've been in touch with Marcia from the exon20 group and she's now given me some info on other trials like the TAK-788 trial at Sloan (which she believes is closed) and the Tarloxotinib trial that is about to begin at the Lombardi Cancer Center.  We are also in the process of getting a second opinion from Sloan Kettering (we got our initial second opinion from them in April 2018, but decided to not go with them because they missed the exon20 insertion diagnosis and were not going to treat with immunotherapy as a result - they apologized, but it was hard to pick them for treatment after that.)

I'm just wondering when all this is said and done and we have information on all these trials, how do we choose the best course?  Are people responding to poziotinib or is taxol the safer option?  I'm a little bummed out because we did not get much direction from the oncologist.  No one seems to have any definitive answers, or frankly, even recommendations. :o(  The oncologist said that she would pick a clinical trial, then taxol, but that just seemed so odd to me to say given she did not know anything about the trials available.  Wouldn't one have to research each one in order to opine that one of them is better than the other (and/or taxol)?  Or is she saying that because taxol is not likely to work?

Any advice would be greatly appreciated. 

JanineT Forum M...
sch1979, I'm sorry the

sch1979,

 

I'm sorry the progression is definitive.  You would need to ask the onc why she suggests the trial first but I would imagine it's because the trial won't always be available while taxol will be there anytime. 

 

After talking over all the options with the oncologists y'all are likely to have a better idea which trial if any would be the best fit.  Obviously there aren't any best or obvious choices or they wouldn't be in trials.  

 

https://www.onclive.com/web-exclusives/poziotinib-shows-encouraging-activity-among-heavily-pretreated-nsclc-subgroup

Although the article is dated sept I think this is from ASCO in May. https://www.jto.org/article/S1556-0864(18)31859-8/fulltext

About halfway down the article HER2 is discussed, https://www.uptodate.com/contents/personalized-genotype-directed-therapy-for-advanced-non-small-cell-lung-cancer/print

 

Choosing the next step after progression is typically a difficult time.  Just know that after a choice is made is typically much less stressful.  

 

All the best,

Janine

Jim C Forum Mod...
Jim C Forum Moderator's picture
Treatment choice

Hi sch1979,

 

I'm sorry that you're not getting as much guidance on the treatment decision as you would like. When looking at trials of relatively new agents, they can be difficult to evaluate since currently there usually isn't much solid evidence to point to a clear favorite. Your oncologist's recommendation may be based on the idea that if the progression is not rapid, then there is time to try a new, unproven agent with potential, and have a more proven therapy available as a backup. Each trial has a set of inclusion/exclusion criteria, one of which may concern the number or type of prior therapies. So the idea is to get into the trial while you meet the entry parameters, rather than immediately move to a drug that may disqualify you for the trial later. Of course, if the cancer is progressing rapidly, then you might want to opt for a more proven treatment, which would include Taxol (or perhaps its sister drug, Abraxane, which for many patients is easier to tolerate, if insurance will cover it).

 

When choosing a clinical trial, the phase of the trial may also have relevance to you. Phase III trials feature drugs which have already shown some efficacy at earlier, smaller Phase I and II trials. You may feel more comfortable with a Phase III trial. On the other hand, an earlier phase trial drug may prove to produce excellent results. There is also the question of the toxicity profiles of the drugs under consideration, so you may want to compare information on the side effects of each.

 

I wish I could say that making such a decision is a straightforward process, but it isn't...it's more of a weighing of advantages and disadvantages given the often slight evidence, then making the best choice under those circumstances. One positive note is that there are more options now than ever before, with research moving at a very fast pace, though of course it is never fast enough.

 

Good luck with the treatment you choose.

 

Jim C Forum Moderator

 

sch1979
Thanks Jim.  I appreciate the

Thanks Jim.  I appreciate the response.  I guess my apprehension about the clinical trial is also that we are going to move away from immunotherapy and that's a tough thing to swallow given how much emphasis there is these days on immunotherapy.  The oncologist told us that there are no studies showing that if keytruda stopped working, another immunotherapy would work.  Is that true?  

JanineT Forum M...
Right, there are no data

Right, there are no data suggesting a sequence of immunotherapies or immunotherapy combos will have efficacy especially when there is a driver mutation. 

Scohn's explanation of his wife's response to carbo/alimta/keytruda which is the same response your uncle had is pretty typical for those with a driver mutation such as egfr and her2.  These responses also correspond with a low percentage of PD-L1 in the tumor.  So yes unfortunately it may be time to move past immunotherapies.  But as scohn also reported his wife has done well on several other drugs including trial drugs targeting her2 and exon 20 deletion and single chemotherapies.  

sch1979
Thanks Janine. We were told

Thanks Janine. We were told he had a high PLD1 expression. For whatever that is worth! 

sch1979
I just wanted to share that

I just wanted to share that today we were told poziotinib is not accepting patients who have had the carbo triplet, and TAK-788 is also not an option.  The oncologist at NYU was pushing JNJ-372 (JNJ-61186372) (Phase 1) and we are also looking at the tarloxotinib trial in DC (Phase 2).   It's hard to choose between these trials and the traditional chemo route.  I'm sharing in case others can benefit/weigh in.

Jim C Forum Mod...
Jim C Forum Moderator's picture
Post-immunotherapy treatments

Hi sch1979,

 

I'm sorry to hear that the two trials you mention are not available. Trials do pop up frequently though, so it's good to keep looking. 

 

As far as moving away from immunotherapy, I can understand your concern in light of all the hype regarding immunotherapy. But traditional chemotherapy can be quite effective, if for no other purpose than to bridge the gap between the initial immunotherapy and whatever new therapy appears in the near future. 

 

Jim C Forum Moderator