Progressed with Tarceva after 9 months. New mutations: l858r and MET H1112R please help with the choice of treatment.

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Vera
Progressed with Tarceva after 9 months. New mutations: l858r and MET H1112R please help with the choice of treatment.

Dear Doctors, could you please help me with the right treatment for newly detected mutation by blood biopsy. This is MET , exon 16, H1112R mutation in combination with my existing one which is exon 21, l858r. It has been reported that those two mutations exist in equal amounts. 

I realy confused and my oncologist as well. I didn’t find any information in the literature about relevance of this type of mutation to lung cancer,but only to renal cancer. I am not sure what treatment I can use to target this mutation. I am currently on Tarceva for 9 months with excellent response ,but now progressed with a few small new bone mets. 

Could you please help me to chose right treatment for me and advise if this kind of met mutation can be  found in lung cancer .

would greatly appreciate your time and knowledge.

many thanks in advance 

 

Jim C Forum Mod...
Jim C Forum Moderator's picture
Progressed with Tarceva after 9 months

Hi Vera,

Welcome to GRACE. I am sorry to hear of the progression of your cancer. I too have not found any references to a link between the new mutation and lung cancer, and there is none listed on the excellent reference My Cancer Genome. With current technology, there are many mutations which can be detected, but the signficance of most of them is as yet unknown, with no targeted therapies available. 

 

I will ask Dr. West if he has any information with regard to this mutation and lung cancer.

 

Jim C Forum Moderator

 

Jim C Forum Mod...
Jim C Forum Moderator's picture
Progressed with Tarceva after 9 months

Hi Vera,

Dr. West responded that this mutation is quite rare and that he has no further information on it.

 

With that in mind, your oncologist will likely want to develop a treatment plan which disregards that new mutation.

 

Jim C Forum Moderator 

 

Jim C Forum Mod...
Jim C Forum Moderator's picture
Progressed with Tarceva after 9 months

Hi Vera,

I understand that for some reason you were unable to post your response, so I am reproducing here (my reply will follow in the subsequent post):

 

Dear Jim, 

i very much appreciate your effort, knowledge and support. Many thanks for asking Dr. West for the advice advice. In this paper is written that thIs MET, H1112R mutation is germline and predisposes hereditarily papillary renal carcinoma. It’s also states : “ It is important to note that patients with germline mutations in theMET gene are predisposed to develop papillary renal carcinoma, type 1 specifically. Those mutations are NOT known to predispose to any other type of malignant disease.”

http://atlasgeneticsoncology.org/Genes/GC_MET.html

So, me and my oncologist quiet confused where to go......?   Afatinib .....?  Tarceva + Cabozantinib.....?  Tarceva+ Crizotinib......?

or any other options? The scientists from Oncodna lab in Belgium said they are sure about those findings and the amount of both medications are similar.

Many thanks to Dr. West for his time and suggestions.

Vera

Jim C Forum Mod...
Jim C Forum Moderator's picture
Progressed with Tarceva after 9 months

Hi Vera,

 

First, I believe that the problem you had in posting was due to the special characters you had inserted just before your name. I was unable to post an exact quote of your reply until I removed them.

 

There are a variety of treatment options at this point. The first question would be whether there is sufficient progression to warrant changing therapy. If the progression is slight, then continuing with Tarceva is a viable option. Or if the progression is limited to one or a few sites, local therapy such as radiation is possible, followed by continuation of Tarceva. If progression is more significant, then the third-generation EGFR inhibitors such as osimertinib or rociletinib have shown efficacy even for patients without a T790M resistance mutation. Another option is standard chemotherapy, either alone or in combination with Tarceva.

 

Afatinib as a single agent after resistance to Tarceva has not shown good results, although in combination with cetuximab it has proven an effective though challenging regimen.

 

Dr. West discusses these and other options in this GRACE video: https://cancergrace.org/post/treatment-options-egfr-t790m-negative-acquired-resistance Certainly plenty of options to discuss with your oncologist.

 

Jim C Forum Moderator

 

Vera
Progressed with Tarceva after nine months

Dear Jim

Many thanks for all suggestions. Much appreciate!

 

Vera
Progressed with tarceva after 9 months

Dear Jim, I think I found the problem withsending messages. It not compatible with my iPad and when I try computer, its working. So happy!

Just would like to clarify Dr. West response: Does he suggests to ignore those newly found MET mutation ? What is about to add crizotinib or cabozantinib to Tarceva. Ive seen the article describing synergetic effect of cabozantinib and tarceva for wild type  EGFR. ?  

Thank you.

Vera

Jim C Forum Mod...
Jim C Forum Moderator's picture
Progressed with tarceva after 9 months

Hi Vera,

 

I don't think this site is incompatible with your iPad, but rather your use of emojis in the replies you attempted to post. Try your next reply from the iPad, without emojis, and see if that works.

 

Essentially what Dr. West was saying is that because this MET mutation is so rare, there is insufficient evidence to draw any conclusions about whether the mutation has any relevance to the treatment of lung cancer, and whether crizotinib would have any value in your situation. But from a practical and legal point of view, he can't tell you what you should or shouldn't do; that would be for you and your medical team to decide.

 

In addition to the article on the Tarceva/cabozantinib combination you cited (which for others who may be interested can be found here ) there is also a report , released just last month, on the use of that regimen for patients with activating EGFR mutations. Although it was a small Phase II trial and further study in a larger, Phase III trial is needed, it showed encouraging results.

 

Jim C Forum Moderator

 

Vera
Progression on tarceva

Thank you, Jim. We have decided to wait until my next scan in June. If there any progression then probably can make sense to add Cabozantinib to Tarceva instead of using Afatinib. I jest afraid of more toxicity because ground glass opacity has been found recently on my healthy lung.

Just wanted to ask question if GGO is drug related what is the usual practice? To reduce the dose or to change the drug....?

Thanks again for your time and support . 

Jim C Forum Mod...
Jim C Forum Moderator's picture
Progression on tarceva

Hi Vera,

 

There are various conditions, not related to cancer, which can cause such ground glass opacities. If you are concerned about Tarceva-induced pneumonitis, that is a serious matter and a diagnosis which your oncologist or pulmonologist will need to make, based not only on the appearance on the scan but also any new symptoms you may be experiencing. The recommended intervention for such pneumonitis is to discontinue Tarceva permanently and initiate treatment with corticosteroids. Although there are reports of patients who have returned to an EGFR TKI after the pneumonitis has resolved, that is a risky  course of action which should only be undertaken after a frank discussion of the risks and other options with your doctor.

 

If you are asymptomatic, this comment by GRACE forum moderator Janine will be of interest:

 

"A new paper on the subject was written in the Journal of Thoracic Oncology that looks at something called transient asymptomatic pulmonary opacities (TAPO). As the name suggests they are talking about a complication that doesn't cause symptoms but looks like pneumonia or ILD but isn't.  If you're not symptomatic then you might want to read this article.  https://www.jto.org/article/S1556-0864(18)30606-3/pdf "

 

Jim C Forum Moderator

Vera
Progressed with tarceva

Thank you very much for all answers! So much appreciate!