Hoping I may get some answers as it seems everything we try is failing for one reason or another.
Stage 4 ROS1 diagnosed Feb 2018 with BM’s treated with SRS. Ceritinib worked so well apart from pneumonitis so had to stop. Carb and Pem but new BMs just treated again with SRS. Lorlatinib and Entrectinib trials excluded because of pneumonitis!
Having to use Crizotinib and hope now.
Have high PDL1 but prob not helpful. Is there a trial in UK sim to Extended access for Entrectinib?
Any experience using TKI with low dose steroid to control the pneumonitis?
When can we expect Lorlatinib and Entrectinib to be available as a treatment ?
Need other options.
Reply # - August 16, 2018, 08:29 AM
Welcome to GRACE. I am sorry to hear of your difficulty finding an appropriate follow-up therapy. As the trial exclusion criteria you have seen reflect, the usual recommendation after TKI-induced pneumonitis is permanent discontinuation of the TKI. But exceptions are made, usually in situations in which there are no other viable treatment options. This study report lists a number of cases in which a TKI has been rechallenged after causing pneumonitis: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805846/ In a number of the reported cases, corticosteroids were administered during the rechallenge, and a good percentage of the patients did not experience a recurrence of pneumonitis.
I don't know that you describe a situation in which there are no other viable options, since only one chemotherapy regimen has been used and immunotherapy, although it has its own risks and generally is not as effective in patients with targetable mutations, could also be an option due to the high PD-L1 expression.
Here in the U.S., Lorlatinib has been granted priority review status by the FDA, and we might see an approval fairly soon. Entrectinib has been fast-tracked, but may take a bit longer to reach general practice.
Reply # - August 16, 2018, 08:33 AM
Perhaps one other point to make, which may be relevant depending on your particular circumstances. When a systemic treatment is well-tolerated and keeping the cancer controlled in the rest of the body, it's not uncommon to treat brain metastases with radiation and continue or resume the systemic treatment. In your case, continuing with maintenance pemetrexed (Alimta) could be another option.
Reply # - August 16, 2018, 09:09 AM
Jim C thank you for your advice. At present we have had a good response to a TkI but pneumonitis intervened after s few weeks. The Pem maintenance does not seem to have worked though the primary has shrunk a small portion on the side appears to have grown slightly too.
We have not reached an end stage but the obvious risk are the brain mets recurring.
It looks as if we are going to try Crizotinib for the first time and hope pneumonitis is not a class effect.
We have spoken about ‘named patient access’ and also SRS to the Primary.
Our options seem to be:
1. Crizotinib +\_ Gamma Knife
2. Hopefully Lorlatinib or similar if fails ( after re biopsy)
4. Chemo again
5. Plus Cyberknife?
6.of TKI (Ceritinib) under steroid cover as in your paper.
7. Trials if they allow prev TKI pneumonitis / Named patient access.
In your experience how does this look and is it feasible and sensible?
How many times could we use Gamma Knife ?
Really appreciate your valuable time and help,
Reply # - August 16, 2018, 09:21 AM
Keeping in mind the pneumonitis risk posed by a TKI, I think your list is certainly reasonable. As far as repeating focal brain radiation, it's really a question answered by your radiation oncologist taking into account your particular circumstances. If the lesions are in the same or very similar location to those previously irradiated, then it may not be feasible in that instance, due to the increased risk of damage to healthy tissue.
Reply # - August 16, 2018, 10:29 AM
Hi R and C,
Welcome to Grace. I'm very sorry you need to be asking these questions. Such an important and immediate need to understand an extremely complicated subject.
SRS is regularly used for brain mets and there are some who have used it successfully a dozen times. But SRS in the rest of the body (including lungs) or any local treatment such as surgery or radiation in stage IV nsclc is typically given to those on a tki: Sometimes a person will do well for months or years on the tki then one or 2 spots will show up (acquired resistance) while all other cancer is being kept under control with the tki. This happens because some of the cancer has acquired resistance to the tki while the rest of cancer is still under control by the tki. In this type of situation radiation or surgery can get rid of the cancer that has acquired resistance allowing people stay on the tki for months or even years.
Since srs still destroys some healthy tissue local srs to the lung is usually reserved to relieve symptoms so not to destroy too much healthy tissue. There's no number of times but must be balanced for the individual.
Any tki or immunotherapy would be considered potentially problematic since your run-in with pneumonitis so a chemo based plan with the understanding srs for any new brain mets would be highest on the list of options. If that doesn't work out a return to a tki (you know it has efficacy for you and don't know if immunotherapy does) with cautionary steroids such as described in the article Jim linked to might be another option.
I don't think we could know for sure which ROS1 tki has least possibility of pneumonitis but the one generally thought to be the least harsh would be choice #2 after chemo.
I hope you do well on Pem for a long time, it's not uncommon.
Reply # - August 29, 2018, 01:04 AM
Thank you for your advice, time and kindness in replying.
We have been advised that Lorlatinib has been applied for on a compassionate basis.
It is now 4.5 weeks since the last Pem infusion and are still waiting for the new medication.
Do you have any idea how long between treatments changing is a safe period?
I realise that this is a very difficult question but hoping you may be able to shed some light on it for us.
I keep agitating to get things moving as very concerned with the delay.
Reply # - August 29, 2018, 11:54 AM
Hi R and C,
You're right. There is no one answer to the question of how long one can go without treatment before the cancer gets out of hand. However symptoms are a pretty good indicator. I know it sounds selfish but there isn't specific data on how long someone can go without anti lung cancer treatment before it's too late to get the full effects of the following treatment. It's not monetarily beneficial for the pharma to see how little of a drug one can use.
However breaks between treatments is a reality oncologists face everyday. The problems arise when a person is too sick to withstand the side effects of treatment more than if the cancer is too widespread for a new treatment to be effective.
That's why it's important to keep the oncology team aware of new or worsening symptoms. Certainly as long as you don't have symptoms from the brain mets it's usually considered ok to hold off on radiation in hopes the systemic treatment will work on the brain mets. As a matter of fact it's becoming more common to see trials set up to accept those with non symptomatic brain mets. Just 5 and 10 years ago that was pretty much unheard of.
Keep up the agitation. The squeaky wheel gets the grease. :) I hope you don't have to wait long, it's often said the waiting is the hardest part.
Reply # - August 29, 2018, 12:58 PM
I am happy to hear your doctor's have applied to Lorlatinib on a compassionate use basis as it is a medication with a lot of promise and just recently
"Pfizer’s lorlatinib clears first hurdle to UK early access scheme"
I also hope they grant you this compassionate use soon. I agree with Janine, the squeaky wheel gets the grease. Keep pushing!