Tarceva with Avastin or Afatinib - 1261844

jls57
Posts:22

My mom has just received her biopsy results which revealed that she is EGFR+. This was presumed as she has had long term success on Tarceva. In December the CT scan showed slight progression in the lungs and a brain MRI revealed 8 mets. She finished WBR in early January and started back on Tarceva two weeks ago while awaiting final results of biopsy. The interesting piece is that she did show any resistant mutations. Is this common? The two options her oncologist is looking at moving forward are: Continue with Tarceva while adding Avastin or Afatinib. Thoughts, insights,opinions, all welcome.

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Reply # - January 30, 2014, 01:38 PM

catdander
Posts:

Hi jls57,

I've pasted your mom's incredible cancer history below as context for our doctors who'll respond.
I'll contact a doctor so you should hear back within the day.
Best hopes,
Janine

jls57, mothers cancer history:
My mother was diagnosed with stage IIIB NCSLC with BAC features in 2003. She is a non-smoker. She had a re-section in December 2003. Jan.-June 2004 she had first line traditional chemo with progression. She was then placed on 150mg of Tarceva in April 2005. DUe to intolerance of side effects the dosage was lowered to 75mg. She has been on 75mg of Tarceva since April 2005 with stable results until Dec. 2012 when via a routine chest CT a lesion on T-9 was discovered. Follow up MRI confirmed it as a met.January 26 2012 chest CT indicated that the lesion had grown and was destroying the bone. Two weeks of radiation to T-9 the first 2 weeks of Feb. 2012. A year later, 2 more mets to spine. Treated with radiation with success. Less than a year later a met showed on hip. 2 weeks on radiation. On the last day of treatment she had a lung CT and a brain MRI which showed progression in lung and multiple brain metastases. Dec2014: WBR and biopsy of primary tumor for mutation testing Next scan for brain is 'March 2014. Currently she is back on 75 mg of Tarceva until decision is reached about new treatment.

Reply # - January 30, 2014, 06:54 PM

drsequist
Posts: 15

jls57,

I'm sorry that your mom is going through this. The area of EGFR mutation positive acquired resistance treatment has seen many advances in the recent years. It's difficult to give a specific recommendation for your mom in a format like this but I would definitely consider a consultation at a center that sees a lot of EGFR acquired resistance patients. There are several drugs in clinical trials right now that are showing good activity (such as CO-1686 and AZD-9291). There are also commonly used strategies that don't require participation in a clinical trial like treatment beyond progression (often the most appropriate if the growth is minimal), and adding chemotherapy to erlotinib, etc. I would say one thing i would not recommend is adding afatinib to erlotinib - there is no safety data on that combination and my guess is that it would not be safe.

Reply # - January 30, 2014, 10:34 PM

Dr West
Posts: 4735

I believe that you were referring to switching to afatinib or else adding Avastin (bevacizumab) to erlotinib (Tarceva). I'd have to say that both of these strategies are unlikely to provide much benefit. As Dr. Sequist noted, there are a few agents in trials that are quite promising, particularly those she noted. We often do consider continuing the EGFR inhibitor and either add chemo or a local therapy like radiation if there's only limited progression and overall still good control compared with where things started. This is a situation where having significant experience might really help, so Dr. Sequist's suggestion about potentially getting an opinion from a center and expert with a lot of experience managing patients with specific mutations like EGFR could really help.

Good luck.

-Dr. West

Reply # - January 30, 2014, 10:34 PM

Dr West
Posts: 4735

I believe that you were referring to switching to afatinib or else adding Avastin (bevacizumab) to erlotinib (Tarceva). I'd have to say that both of these strategies are unlikely to provide much benefit. As Dr. Sequist noted, there are a few agents in trials that are quite promising, particularly those she noted. We often do consider continuing the EGFR inhibitor and either add chemo or a local therapy like radiation if there's only limited progression and overall still good control compared with where things started. This is a situation where having significant experience might really help, so Dr. Sequist's suggestion about potentially getting an opinion from a center and expert with a lot of experience managing patients with specific mutations like EGFR could really help.

Good luck.

-Dr. West

Reply # - January 31, 2014, 05:59 AM

jls57
Posts: 22

Yes, Dr. West, I was referring to either taking Afatinib or staying on Tarceva but adding Avastin with it. Thank you for making that distinction. One more question, what does it mean that her biopsy indicated that she was not showing resistance?
Thank you so much Dr. West and Dr. Sequist for responding.
jls57

Reply # - January 31, 2014, 06:33 AM

JimC
Posts: 2753

Hi jls57,

Since no resistant mutations were found, it may mean that your Mom's cancer has an EGFR-related component and one that is caused by other mutations, and the latter component is the one that is progressing. If that's the case, standard chemo may be able to bring the non-EGFR component under control while Tarceva continues to control the EGFR component. Or it could simply mean that the biopsy sample (especially if it was small) may have missed the EGFR resistant cells.

JimC
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Reply # - January 31, 2014, 07:47 PM

jls57
Posts: 22

Thank you Jim for explaining that. I am guessing that is why the oncologist would suggest pairing Tarceva with Avastin, with the assumption that Avastin would target the non-EGFR component? Although it sounds like it would not necessarily provide any benefit. Do the treated brain mets pose an extra challenge in finding a successful treatment? Has Afatinib proven to cross the blood brain barrier like Tarceva can?

Reply # - January 31, 2014, 10:01 PM

Dr West
Posts: 4735

No, afatinib isn't known to be particularly effective against brain metastases. I don't think Avastin without chemotherapy is especially likely to treat the EGFR TKI-resistant component very effectively: Avastin as a single agent isn't a particularly effective treatment against lung cancer. It would be more typical to switch to chemotherapy or add chemotherapy-based treatment to an EGFR inhibitor. However, if the progression is still pretty slight, I've added Avastin to Tarceva to try to just act as a potential modifier to escalate EGFR TKI activity, and I've seen a patient go from slow but steady progression on Tarceva alone to stability for 6-8 months on the Tarceva/Avastin combination. So I think just adding Avastin is an option to consider, but I don't think it's likely to have a dramatic impact. That may still be OK.

Good luck.
-Dr. West

Reply # - February 3, 2014, 11:30 AM

jls57
Posts: 22

After a lot of research and of course the wealth of knowledge and information from this forum, I am thinking the "best" option would be to try to get my Mom into a clinical trial. I found one for AZD-9291 that is phase 1 and currently recruiting. According to the criteria she should qualify. Is there anything else I should be aware of entering into the clinical trial realm?

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