progression reasoning

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daxys
progression reasoning

Hello everyone,

I would like to ask a question about my mums progressions to  make sure that my reasoning about my mother’s progression is OK :

 

My mother (73)  was diagnosed with NSCLC IV.stage in April 2016 extensive tumor in both lungs (main tumour and many small/tiny lesions) and mediastinum, without distant methastases, only in lymph nodes)   -   EGFR positive –mutation exon 18- G719X  - more info here : https://www.inspire.com/m/daxys/

 

She  was for 21 months on Afatinib (40% tumour reduction), which was stopped after only slight and slow progression (only three lung metastases grew by 1-2,5 mm). Then she had 3 infusions of pemetrexed within 2 months and after that she was  for 1,5 month without any treatment for lungs.  In these 3,5 months (pemetrexed and no treatment)  she had 50% growth of the tumor (main tumor grew from 32x17 to 40x23 mm).

After that  she was on osimertinib for almost 2 months – CT showed that everything was stable after 2 months on osimertinib except for 2 lesions in lungs  (which grew from 6 to 10 mm  and 11 to 15 mm).  Despite the fact that osimertinib stopped overall progression, the oncologist stopped it and started  carboplatin  monotherapy.  After 3 weeks of no treatment and 3 weeks with one infusion of Carboplatin  a major overall progression was shown on an X-Ray scan (some lesions by 100%). 

 

To me it seems obvious  that the original mutation ex.18-G719X  was and still is  responsible for the most of the growth we have had. G719X was detected in the liquid biopsy in June 2018 (the only mutation detected). The overall growth always happened when we stopped blocking it by afatinib and later by osimertinib (osimertinib was tried despite  T790M was not detected and she is probably T790M negative).  The progression on osimertinib was limited and happened in different lesions than the progression on Ist line afatinib. I also think that our time on osimertinib was quite short for other progression mechanisms to develop.

 

 

Could I please ask someone  whether there is anything wrong about my explanation of my mums progression and ex.18-G719X  being responsible for the most of it ?

 

Jim C Forum Mod...
Jim C Forum Moderator's picture
progression reasoning

Hi daxys,

I think your reasoning makes quite a bit of sense. As you note, significant progression occurred in the absence of an EGFR TKI. Although we would like to be able to better predict the efficacy of a proposed line of treatment, at times we are left with a process of trial and error, so when a patient's cancer responds twice to EGFR inhibitors and progresses significantly on alternative therapies, the implication is clear.

Unfortunately, I think your mum's experience illustrates the wisdom of trying to get the maximum benefit from each effective line of therapy. When there is slow progression on a well-tolerated agent (as is often the case with EGFR TKIs), it may be a better choice to continue the TKI until progression becomes more significant (as in Dr. West's analogy -  bad breaks vs. no brakes).

With that in mind, you might even consider returning to one of the previous TKIs, as there is some evidence that rechallenging a TKI that was effective may lead to further response, albeit usually shorter in duration.

Jim C Forum Moderator

daxys
progression reasoning

Thanks a lot for your response Jim!  I really need to be reassured my explanation of progressions is OK.  Unfortunately, as you say, it seems that   my mum's case illustrates how it makes sense to stay on a TKI when the progression is limited. This is one of the  things  Jack West says here on CancerGrace (the kind of information we cant find easily from other sources and that makes CancerGrace so great).

Unfortunately we learned it the hard way.  In our country TKIs are stopped being prescribed and covered by insurance after first signs of progression on them.  That's why we could not continue on afatinib (I did not know at that time there is an option to get affordable  generic Afatinib from Asia)

Now I want my mum to get back on Afatinib for retreatment. I purchased generic afatinib for that.

Retreatment with the same TKI after a holiday from it is shown in some studies as a strategy that could help buy time. Here is a study that I found  where it proved to be benefitial to almost 80 % of patients (with gefitinib or erlotinib - I have not found a retreatment study for afatinib yet).

Effect of EGFR-TKI retreatment following chemotherapy for advanced non-small cell lung cancer patients who underwent EGFR-TKI

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4296083/   In the same-drug group, 1 case had CR (7.6%), 2 cases had PR (15.4%), and 8 cases had SD (61.5%); RR was 23%. There were 2 cases in PD (15.4%), DCR was 84.6%, and mPFS was 5 months.

So Afatinib makes most sense to me now when the progression still seems to be driven by the original mutation. I hope it will be able to stop current rapid progression in my mums lungs.

Jim C Forum Mod...
Jim C Forum Moderator's picture
Progression reasoning

Daxys,

I hope your mum gets a great response to afatinib again!

Jim C Forum Moderator 

JanineT Forum M...
Best of luck to your mom

Best of luck to your mom Daxys.