When to stop Iressa? - 1267882

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peterkin102
When to stop Iressa? - 1267882

My wife with stage IV NSCLC since May 14 had complete resection of her left upper lobe Adenosquamous cancer and mediastinal lymph nodes on 18 December 2014. The tissue studies showed she had Adenosquamous (90% squamous ) carcinoma. Her lymph nodes were cancer free. Pathology staging T2 (2.5cm) N0. In addition to the existent Positive EGFR exon 21, there was development of T790M mutation.
Right now there's no more detected cancer in her (temporary? hope for permanent reprieve) and she had resumed her Iressa a day after her surgery. She had a left chest wall mass that was removed in June 2014.
Her onc has advised her to stop the Iressa immediately and permanently.
She's due for adjuvant chemotherapy with Cisplatin and oral Vineralbine in ten days time.
My question is should we stop the Iressa? Before and after the chemotherapy ?
We are afraid of flare up of the cancer and there maybe remnant EGFR cells that might still be susceptible to the Iressa.
Thanks for your input.
Peter.

JimC
Hi Peter,

Hi Peter,

I'm assuming that her doctor wants her to stop Iressa because of the T790M mutation, which confers resistance to EGFR TKIs such as Iressa or Tarceva, preferring instead to provide standard adjuvant chemo.

The "flare" that I'm sure you've read about tends to be an issue for patients who have had a long response to an EGFR TKI, and with the surgery your wife has had (and the relatively short time since diagnosis) I don't think you could necessarily say that she has had such a sustained response such that ending the TKI would result in a flare.

JimC
Forum moderator

<p>I began visiting GRACE in July, 2008 when my wife Liz was diagnosed with lung cancer, and became a forum moderator in January, 2010. My beloved wife of 30 years passed away Nov. 4, 2011 after battling stage IV lung cancer for 3 years and 4 months</p>

Dr West
The presence of a T790M

The presence of a T790M mutation suggests that her cancer has become resistant to Iressa (gefitinib).

If surgery was done, the idea was that there is a meaningful chance of getting rid of all of the cancer. As I see it, if someone is having a surgery for stage IV cancer, there has to be a presumption of "getting it all", which also means that there needs to be an end date to systemic therapies. If systemic therapy is felt to be needed forever, that's basically saying that nobody really believes that the surgery did what it was supposed to do.

Overall, then, I'd say if someone is committing to surgery for stage IV disease, they should not stay on ongoing systemic therapy without an endpoint, especially if there is evidence of acquired resistance to it.

Good luck.

-Dr. West

+++++++++++++++++++++++++
Dr. Howard (Jack) West
Associate Clinical Professor
Medical Oncology
City of Hope Cancer Center
Duarte, CA

Founder & President
Global Resource for Advancing
Cancer Education

carrigallen
I agree with the oncologist

I agree with the oncologist about stopping the Iressa. If the cancer is destined to come back, then the Iressa will not change this. Only time will tell, what will happen with the cancer over the next year or two. Hopefully she will have a great remission.

peterkin102
Thank you Jim, Dr. West and

Thank you Jim, Dr. West and Dr. Creelan for your clear arguments against resuming Iressa.
We have stopped the TKI and are proceeding for chemotherapy next week. We are always trying to be a step ahead of the cancer. As she's confirmed to have T790M gateway mutations there's hope that if the cancer does return there are options in the third generation TKIs now undergoing trail. As she has no detectable and measurable cancer now she's not eligible for the trails. We hope she will never need to go down that route.
We are most grateful for all your opinions that is helping us stay the right course.
Peter.

peterkin102
Dear Jim, Dr. West and Dr.

Dear Jim, Dr. West and Dr. Creelan
My wife's brain MRI today show a one cm metastatic nodule in her right pre frontal cortex close to the edge of the brain with surrounding oedema. She has no neurological deficit.
She's due for PET scans in three days time. Meanwhile MRI scans of her abdomen were clear.

The last scans in early December 14 was clear.
Is It important to know how long the brain metastasis
has been as her excised lung tumor then showed T790M mutation?
If this brain met was from an earlier spread before formation of the resistant mutation then might radiotherapy suffice?

May I enquire:also how do we know if her met is synchronous or metachronous?
Do you think if her PET scans show only one area of brain metastasis would surgey or SRS or combination Helps?
Do you think resumption of TKI would be of benefit esp if the metastasis is non T790M?

Thanks so much for you opinion.
Regards

Peter.

JimC
Hi Peter,

Hi Peter,

I'm sorry to hear of the discovery of this brain metastasis. If she had a previous brain MRI which did not reveal its presence, and since she was diagnosed in May 2014, that met would be considered metachronous. As Dr. West has described the difference as:

"synchronous metastases, meaning that the ... met was present when they first found and treated the main tumor in the chest, and metachronous lesions, which are mets that were not present initially but became evident an interval of time after a patient’s initial presentation and treatment (actually, a cutoff of six months is the usual definition of synchronous vs. metachronous)."
- http://cancergrace.org/lung/category/lung-cancer/general-lung-cancer-iss...

Often in situations in which there is only one area of progression while being treated with a targeted therapy, local therapy such as surgery or radiation is utilized, since it may be that the cancer is otherwise well-controlled by the systemic treatment. In your wife's case, radiation to the single met would likely be recommended.

There's really no way to know if the brain met represents T790M-driven resistance other than to biopsy the lesion. If that met is the only evidence of progression, and since radiation rather than surgery is usually preferred for such a lesion, it may be that radiation will be chosen followed by continuation of the current therapy and close surveillance. If later there is further evidence of progression, then perhaps a biopsy will be appropriate.

JimC
Forum moderator

<p>I began visiting GRACE in July, 2008 when my wife Liz was diagnosed with lung cancer, and became a forum moderator in January, 2010. My beloved wife of 30 years passed away Nov. 4, 2011 after battling stage IV lung cancer for 3 years and 4 months</p>

peterkin102
Thank you Jim for your

Thank you Jim for your erudite reply.
We plan to do SBRT if that's the only solitary lesion outside her thorax.
We are also considering pulse Tarceva in trying to get the drug through the BBB.
if another lesion emerge than we would perhaps biopsy that as it might be T790M driven?
What is your opinion on pulse therapy?
Thank you
Peter

catdander
While this question has been

While this question has been asked on Grace before, me finding it might be like looking for a needle in a haystack. There are no lung specialists using pulsed tarceva to treat brain mets and no data to suggest it's preference. Instead most prefer to use cyber knife for 1 to 4 or so mets in the brain.

Janine

peterkin102
Thank you Janine for your

Thank you Janine for your prompt reply.
We would certainly do the cyber knife.
Could you enlighten me on two burning questions?
My wife though 53 years old is fit as a fiddle certainly fit for another surgery 4 months from her previous in December. At that time it was confirmed she had developed T790M mutations. This would excision biopsy for this if solitary brain lesion and subsequent targeted therapy based on this latest biopsy be a prudent move?perhaps this could be followed by SBRT to the cavity as I believed this combination therapy resulted in less recurrence?
My wife being Adenosquamous (90% squamous) though none smoker could she be a suitable candidate for Novulomad?
Thanks so much for your feedback.
Peter

JimC
Hi Peter,

Hi Peter,

Focused radiation such as CyberKnife is the treatment of choice for a solitary (or a few) brain met(s). It tends to be effective and safe, and most likely to produce results in a timely manner. If there are more than three or four mets, then whole brain radiation (WBR) is usually recommended.

Pulsed Tarceva has been used mainly in an attempt to get effective doses of Tarceva into the cerebrospinal fluid to treat leptomeningeal carcinomatosis (LMC), a condition in which cancer cells have infiltrated that fluid. While WBR tends not to be effective against LMC, some patients have derived a benefit from pulsed Tarceva. It did not seem to help in my wife's case, although in addition to LMC she had also had a recurrence of many brain metastases as well as rapidly progressing lung cancer in the rest of her body.

Since Nivolumab has been approved for pretreated squamous lung cancer and your wife's cancer is 90% squamous, it certainly seems that it would be an option.

JimC
Forum moderator

<p>I began visiting GRACE in July, 2008 when my wife Liz was diagnosed with lung cancer, and became a forum moderator in January, 2010. My beloved wife of 30 years passed away Nov. 4, 2011 after battling stage IV lung cancer for 3 years and 4 months</p>

peterkin102
Hi Jim,

Hi Jim,
my wife had SBRT to her two brain mets in April this year but the two mets had progressed with increasing size and cerebral oedema. she had developed weakness of her left upper limb. she had two craniotomies to remove the two mets. MRI scans today showed they had been removed completely and the oedema are subsiding. she's well now with no weakness and has been off Dexamethasone. her PET scans a week again showed no cancer elsewhere in her body. the mets pathology showed also squamous carcinoma EGFR exon 21 positive as was seen in her primary lung cancer. no T790M mutation this time.

so evidently there's no measurable cancer now in her body.
what I can't understand is why did she not response to SBRT at all? and should she undertake further radiotherapy to her tumour beds?
could it be that the dosing for her SBRT was inadequate?
Would she response to Gamma Knife instead if she gets a relapse in her brain?
Thanks
Best Regards.
Peter

JimC
Hi Peter,

Hi Peter,

Great news that the PET scan showed no evidence of cancer anywhere in your wife's body! We're always happy to hear about and celebrate such a terrific update.

It's hard to say why SRS (Stereotactic Radio Surgery, which is what it's called when directed at brain tumors) failed. I've read that it has a success rate of 80-90%, so these mets may just be an example of the lesions that don't respond. Gamma Knife and Cyber Knife are trade names for SRS/SBRT technology; one of those is likely what was used for your wife's brain mets.

Since SRS is non-invasive and tends to have fewer side effects, it would probably be tried again in the event of a recurrence, although that's something you'd want to discuss with your radiation oncologist at the time.

Once again, congratulations and thanks for sharing your good news!

JimC
Forum moderator

<p>I began visiting GRACE in July, 2008 when my wife Liz was diagnosed with lung cancer, and became a forum moderator in January, 2010. My beloved wife of 30 years passed away Nov. 4, 2011 after battling stage IV lung cancer for 3 years and 4 months</p>