When to stop Iressa? - 1267882

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

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

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.

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-is…

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

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

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

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