Recommended 2nd line treatment for EGFR patient with bone and brain metastasis - 1264667

future1
Posts:8

Hello, my Mom, 63, non smoker with EGFR exone 19 mutation. Since illness discovery (Jan. 2013) taking Tarceva and until recently stable- feeling well, active, working. Recently Brain MRI showed significant change in findings in the Dura (left and right hemisphere) and around the left eye. We are looking for the best treatment for her to hold back progression in the brain from one hand, but also to maintain as much as possible her quality of life. Possible treatments that we heard:
- Of course WBR- how effective? How severe are the side affects?
- to add Avastin to Tarceva
- start Afatinib- how effective can this be with brain metastasis?
- test for T790M mutation and try clinical trial

I would appreciate your inputs on these above options, and perhaps recommendation and other options that we didn’t consider.
Many thanks for your urgent response

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Reply # - June 29, 2014, 12:10 AM

Dr West
Posts: 4735

I'm very sorry to hear of your mother's progression.

I'm afraid that treating disease within the central nervous system (CNS) is very difficult to do effectively. WBR side effects vary from person to person, but it is the overwhelming leading choice when the alternative is near certain disease progression in the CNS. There is no evidence that adding Avastin (bevacizumab), switching to afatinib, or a clinical trial would be helpful. I think there is very little reason to suspect that there is any meaningful probability of benefit with the first two options, and the vast majority of clinical trials exclude patients with uncontrolled CNS disease, and exclude most patients with leptomeningeal carcinomatosis (the dura are part of the meninges) under any circumstance.

There has been very limited work that has shown cases of EGFR mutation-positive patients with leptomeningeal carcinomatosis responding to pulsed Tarceva (erlotinib) given as 600 mg (four tablets) once every four days (no Tarceva on the other 3 days of every 4), but it isn't widely recognized as a consistently effective treatment option at this time. You can read more about it here:

http://cancergrace.org/lung/2010/01/31/an-effective-treatment-for-some-…

http://cancergrace.org/lung/2011/11/03/pulsed-tarceva-for-lmc/

Good luck.

-Dr. West

Reply # - July 7, 2014, 04:09 AM

future1
Posts: 8

Thank you, Dr West.
As there is no progrssion anywere else but the brain, my Mom's doctor recommended Radiation therapy to the Dura, trying to avoid WBRT. Can Mom still take Tarceva while doing the 2 week's radiation treatment? We are concerned that stopping Tarceva will allow the disease to accelerate.
Many thanks for your caring response.

Reply # - July 7, 2014, 09:23 AM

JimC
Posts: 2753

Hello future1,

The side effects of WBR, especially cognitive deficits, are often overstated although they do occur in some cases. In my wife's case, the main side effect was significant fatigue that lasted for several months. This seems fairly typical. There is a GRACE FAQ on the subject here: http://cancergrace.org/radiation/2010/09/13/radiation-faq-what-side-eff… My concern would be that using focused radiation would miss areas of metastasis or micro-metastases that WBR might successfully treat, requiring subsequent use of WBR in any event.

Although each situation is unique, in general oncologists seem to favor stopping Iressa/Tarceva during radiation since they can be radiosensitizers, increasing the effects of the radiation beyond what is desired or safe. As Dr. Weiss has said:

"I do not use tarceva concurrent with radiation in my practice. I fear safety issues, and also the potential for tarceva to keep cells out of cycle (not dividing) at time when radiation is being given (when you'd like them in cycle and therefor more susceptible to radiation)." -http://cancergrace.org/forums/index.php/topic,11108.msg90945.html#msg90…

In discussing trial results in which Iressa was combined with radiation, Dr. West stated:

"There really may be harmful interactions of EGFR inhibitors with radiation that we may not understand. I don’t think these results are clear enough to raise alarms, but it certainly suggests that we should be cautious about presuming that combining treatments is definitely a fine idea." - http://cancergrace.org/lung/2011/01/03/adding-egfr-inhibitor-therapy-to…

[continued in the following post]

Reply # - July 7, 2014, 09:26 AM

JimC
Posts: 2753

[continued from the previous post]

Dr. West added:

"I favor avoiding an overlap between EGFR inhibitor therapy and radiation if it's feasible to avoid it. There really isn't a lot of data, but without data that really reassures us it's safe, I am not comfortable just presuming it will be. Potentiation of radiation effects (potentially good, potentially bad) or development of unforseen complications is very possible if a systemic therapy is combined with radiation in an unstudied way." - http://cancergrace.org/forums/index.php?topic=11439.msg94571#msg94571

In the same thread, Dr. Pennell offered an alternate viewpoint:

"This is a great question, and one which seems more defined by practice pattern than real data.

In Cleveland we have been treating people for years with radiation and concurrent Tarceva as part of a clinical trial, and generally this has been very well tolerated. I have also needed to treat a number of patients with known EGFR mutations quickly because of major symptoms and was unable to wait for radiation to complete for safety reasons. In these cases as well, the side effects appeared to be essentially what you would expect from both modalities but not worse than expected for either.

One of our radiation docs routinely asks patients on Tarceva to stop prior to radiation, while the other one does not. I have no real opinion about it other than that my (admittedly anecdotal) experience is that it seems to be safe, and I do not routinely stop it for short courses of radiation. On the other hand, for stable patients who need radiation at diagnosis, I usually wait until the finish before starting it.

I would love to have some actual data to guide me!"

JimC
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Reply # - July 7, 2014, 09:24 PM

bobradinsky
Posts: 144

Dear Future1

I too am sorry to learn of your mother's progression. My wife, Beth, also a non-smoker, was also EGFR positive, taking Tarceva for mets to bone, liver and brain. She was 64 at the time of onset. Ten months into treatment we discovered progression to her CNS or LMC. She unfortunately passed away last September but I still follow Grace to offer support to patients and caregivers who are dealing with this difficult complication. If I can be of any assistance to you in any way just ask or look up her threads. I wish your mom and your family good luck in the fight ahead.

Bob

Reply # - July 8, 2014, 11:14 AM

Dr West
Posts: 4735

With Jim's addition of the discussion from MD Anderson, that's really the full extent of what we know. Even with that additional information, I think most people feel the same way we did a few years ago: if we can avoid giving these treatments concurrently, that's our preference.

and yes, the dura are part of the meninges, so dural involvement is really the same as leptomeningeal carcinomatosis.

Good luck.

-Dr. West

Reply # - July 8, 2014, 08:43 PM

bobradinsky
Posts: 144

Future1

I just jumped on and see that Dr. west had answered your question about mets in the dura. My wife's LMC was diagnosed with a spinal tap after she started having bad headaches. Radiation was not an option for her so she was put on a pulse dosed Tarceva plan. The radiation sounds like a good option but I'm sure it has it's own set of complications and whether you do it concurrently with Tarceva is beyond my pay grade.
I defer to Jim and Dr. West.

Hopefully I can help you with symptom management and recognition.

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