Afatnib v. Tagrisso for Stage 2B rare EGFR mutation, G 719X Adenocarcinoma lung cancer

Wed, 03/30/2022 - 13:50

Afatnib v. Tagrisso for Stage 2B rare EGFR mutation, G 719X Adenocarcinoma lung cancer Diagnosed with Lung Cancer in January, 2021.

 

Had been a smoker but had not smoked for 35 years prior to diagnosis. Had upper left lobectomy and found to be Stage 2B -- cancer found in 1 lymph node. After lobectomy, I had by 4 rounds of Cisplatin and Vinorelbine (known as Navelbine in the US). I have a rare EGFR Mutation, G719X, and in October began Tagrisso 80mg daily. However, my readings have led me to a medication, Afatnib, which seems to have higher efficacy in the metastatic setting for my particular mutation. I also realize this is a more difficult TKI to tolerate than Tagrisso, which I've had an easy time tolerating.

 

I've talked to my oncologist in Canada and he will not change me over to Afatnib since he cannot find clinical evidence to use it in the adjuvant setting. I am trying to seek second opinions in Canada about the most effective TKI for me - and having a difficult time making contact with an oncologist who is familiar with this mutation and studies. ((I'm sad to say that our health care system in Canada is broken and second opinion referrals are hard to come by)). Feeling a bit exhausted from these efforts!

 

Also should add that I'm a 68 year old female. As a result of chemo, I've had hearing loss and experience some neuropathy in both feet but it doesn't keep me from exercising! I do feel quite good otherwise and have no other limitations, thus far, from the cancer.

 

Thank you for listening!

JanineT Forum …

Hi AbbyAnnie,

I've asked Dr. West to comment.  Following is just what we've already talked about.  I just wanted it to all be in the same place. 

 

I don't know if you've seen this on our youtube channel, I don't think it's made it to our website yet.  It's a 20 minutes piece from the Targeted Therapies Forum last year.  I know it doesn't fit to your specific issue of early stage but it does give an excellent view of what is happening with some of the rare mutations today.  I'm always surprised at the information I get that was unexpected.  From a caretaker's perspective, I know how frustrating it is to have to make decisions from an incomplete understanding of the options.  An experienced head can make all the difference. 
 
 
Janine

Dr West

AbbyAnnie,

It's worth highlighting what is known and what is still unknown here. The role of the chemo is pretty established, and of course you've already gotten that. Many lung cancer specialists would start by saying we shouldn't forget about what has a proven survival benefit, even if it's not sexy targeted therapy. The chemo you received was perfectly by the book and appropriate.

As for the Tagrisso (osimertinib), we know that for people with the more common EGFR mutations, taking it for up to 3 years was associated with a lower risk of the cancer coming back while people were on it...but we don't know if it leads more people to live longer compared to only treating people if/when their cancer comes back and not treating people otherwise. It's not at all surprising that Tagrisso leads to short term benefits while people are on it, but that's not the real test...we know it does well in the short term, but the real question is whether people are cured or just have scans look better while they're on it, then have the cancer come back and have the same survival as the people who didn't take Tagrisso for years.

Still, Tagrisso has become a standard of care as we give patients the benefit of the doubt and hope/presume that the outcomes will be better long-term, as we wait to learn that.

Now, as you know, your cancer harbors a mutation for which Gilotrif (afatinib) has been FDA approved, but it would be a mistake to misinterpret that this means that it's the overwhelmingly best treatment for this cancer. There has never been a direct comparison of Gilotrif and Tagrisso against each other for patients with this uncommon EGFR mutation, but the limited available evidence indicates that Tagrisso has pretty comparable activity for this population. The fact that Gilotrif is specifically approved for this setting and Tagrisso is not has more to do with corporate priorities than an absolute truth that Gilotrif is better. Tagrisso has a huge amount of data supporting its use for the vast majority of the EGFR mutation-positive patient population, so the sponsor company hasn't been focused on the little sub-market that the sponsor company for Gilotrif has to prioritize. I would say that many people who are major experts in lung cancer favor Tagrisso over Gilotrif for patients with these mutations, if both are available.

Part of that is because Gilotrif is notoriously challenging to tolerate, and Tagrisso is generally experienced to be pretty easy to tolerate. That's especially important when you're talking about treating people for YEARS to address a disease that they may not actually still have anymore. People have much lower tolerance for chronic medications in the "adjuvant" (post-operative) setting, since you can't know if it's working or you're already cured and can't get more cured. One trial of adjuvant Gilotrif in patients with more common EGFR mutations found that a huge fraction of the patients just couldn't/wouldn't stay on it more than a few months, let alone the 3 years that is the protocol for Tagrisso.

I would conclude that although Tagrisso is not specifically studied for post-operative use for someone with an uncommon EGFR mutation:

1) Tagrisso and Gilotrif are pretty comparable in how they work against an uncommon EGFR mutation like G719X
2) Tagrisso is covered for post-operative use, and Gilotrif is not
3) Tagrisso is overwhelmingly more compatible with long-term use in this setting, and the limited experience we have is that people will not/cannot take post-operative Gilotrif for long, not knowing if it's helping, while experiencing side effects from it

I hope that helps.

Good luck.

-Dr. West