Irressa for NSCLC with bone metastasis - 1262395

Hi Chen,

Welcome to GRACE. It's good to hear that your dad's cancer is no longer visible in the lung. When treatment eradicates cancer in one or more locations but there is progression in others, it is called a "mixed response" to that treatment. It is likely that some of his cancer cells are sensitive to Iressa, while others may not be. It is a common enough result that Dr. West has written a post dealing with that issue: http://cancergrace.org/lung/2012/08/02/heterogeneity-and-mixed-response/ He also describes how he handles mixed responses in this podcast: http://cancergrace.org/lung/2013/01/01/mixed-response-video/

Radiating bone metastases is done to relieve pain. As Dr. West has said:

"Treating the underlying cancer with chemotherapy and/or targeted therapy (systemic, or “whole body”) can also lead to improvement in disease in the bones, but sometimes local therapy is indicated. The goals of treating bone disease are primarily to relieve pain and to reduce the risk of fracture, which tends to occur in “weight-bearing” bones like the legs, hips, and spine." - http://cancergrace.org/lung/2007/02/17/bone-metastases-in-lung-cancer-a…

In addition to the possibility of radiating the bone mets, your dad's oncologist may consider changing his systemic therapy, although he has had such a good response in the lung that might not be advisable. Some oncologists will consider adding a conventional chemo agent to the targeted therapy (in this case Iressa) in an effort to control the cancer cells which are progressing. That is something he will probably want to discuss with his oncologist.

JimC
Forum moderator

Exactly right on all counts. The key with a mixed response is to weigh the extent of progression vs. response, combined with consideration of available alternatives.

If a decision to change systemic therapy is made, here is a discussion of the leading options:

http://cancergrace.org/lung/2012/08/05/acquired-resistance-faq/

Good luck.

-Dr. West

I would also add that there can be small areas of unimpressive, non-specific activity on bone scans or PET. This kind of low-level activity doesn't necessarily mean progressive bone mets. Any bone inflammation can cause scan activity. It all depends on the context. Usually the lung is the more reliable marker of drug activity, and in this case it sounds like he is doing well. In fact clinical trials do not usually like to measure bone lesions, because they are unreliable for assessing drug response.

Hi Chen,

As you can read in the link Dr. West provided earlier in this thread, the first question is whether there is significant enough progression to warrant a change in treatment. It is not uncommon for cancer to progress so slowly on a targeted therapy that continuing that therapy is preferable to switching to a drug whose efficacy for that patient is unknown. The nodules you describe are still fairly small and they have not grown very rapidly. As Dr. West said in posted he referenced:

"Is the pattern of progression very limited, such as just one or a few lesions growing, or much more diffuse? Is the progression very indolent, such as just a few millimeters of change between scans done 2-3 months apart, or faster than that? And is the person with progression experiencing symptoms or not? And how well are they tolerating the targeted therapy?"

All of the options you list, including staying the course with Iressa, are reasonable possibilities. Although it's true that a nodule greater than 1 cm in size can be large enough to be biopsied, your father's nodules are not much larger than that so it may be difficult to get sufficient tissue to identify genetic changes causing resistance. And it would be good to know if there is a T790M mutation before trying one of the acquired-resistance agent trials.

I hope you have a good meeting with your father's oncologist.

JimC
Forum moderator

Hi Fischer,

It is certainly possible that even if the initial treatment your dad receives in the trial is chemo, he may be able to take AZD 9291 in the future. First, you may want to inquire whether the trial allows those patients who do not respond to chemo to crossover and get the trial drug. In addition, at the time he concludes his participation in this trial there may be new trials available for which he qualifies, or perhaps AZD 9291 will have been approved by then and he can receive it outside a trial setting.

If he tests negative for T790M, there likely would not be another inhibitor available that would be likely to be any better than standard chemo, unless another mutation is discovered for which there is a drug targeting that mutation. He could take Afatinib, another approved EGFR inhibitor, but as Dr. West has often said, it's efficacy in patients for whom Tarceva or Iressa has stopped working has not been impressive.

In the meantime, we'll hope for continued response to Iressa and perhaps a chance to receive AZD 9291 in the trial.

JimC
Forum moderator

Hi Fischer,

In a case in which molecular testing finds mutations which confer both sensitivity and de novo resistance to an EGFR TKI such as Iressa, the response rate tends not to be good, but that doesn't mean there aren't patients who do respond. Apparently your Dad was one of those patients, and that's good!

As far as why his doctor initially chose Iressa, though two years doesn't seem all that long, the study of mutations and targeted therapies develops rapidly, and much more is known now about EGFR mutations in general and de novo T790M mutations in particular.

An acquired T790 mutation appears in response to treatment with an EGFR TKI, while a de novo mutation is there prior to the cancer diagnosis. Dr. West delivered a presentation on the difference and although I can't seem to find the presentation itself, the slides from that presentation are quite informative.

As far as using AZD9291, Dr. West has said:

"Only a very small proportion of patients with lung cancer have a “de novo” T790M mutation at the time of diagnosis, pre-EGFR inhibitor therapy. These patients tend to not do well with Tarceva (gefitinib) or Iressa (gefitinib), though they should have a much better chance of doing well with AZD9291 or rociletinib." - http://cancergrace.org/topic/navelbine-hard-to-tolerate#post-1267953

JimC
Forum moderator

Hi Fischer,

I haven't responded to your thread but have read it and want to say how good it is to know your dad has done well on iressa. These questions haven't been fully answered yet however in the last 2 years more is known. Still trying iressa appears to have been worth it, as your dad shows.

It's likely trialists would want to see what the cancer looks like today since the cancer biology has a tendency to change over time so a biopsy at the time of a trial has become more than likely be needed. Though each is different and you should always ask.

I understand chemo platinum doublet doesn't have the best reputation of and there's certainly reason for that. But even with having to go in to a cancer center to receive treatment IV, the side effects are usually very manageable if you stay on top of them and it is still the official proven next best step in the dad case. So it's not like loosing the lotto as much as it's buying time until the next best thing. Or maybe it's just a glass half full take on a bad situation.

All best,
Janine

Hi Fischer,

None of the GRACE staff can offer an opinion on which option would be best; but we can provide information and observations which help with the decision.

The progression you describe is not especially fast, so sticking with Iressa for now is not a bad option. In its favor is the principle that we like to get as much benefit from each treatment regimen as possible, even if there is mild progression. As Dr. West puts it, "bad brakes are better than no brakes."

Some trials take quite a while (many months) to accrue all their patients, so it is possible that if the progression continues you might be able to enter the trial, or perhaps another trial of the same or a similar drug. As far as recruiting 3-4 from your cancer center, I would expect that number to be at least somewhat flexible, especially if the sponsor is having trouble getting enough recruits from other centers.

If you choose the trial and enter it, neither option is bad and although "cancer can do anything" I wouldn't think that chemo would change the EGFR characteristics of your dad's cancer, since that chemo is not targeting EGFR, possibly pushing it to further mutate. If your dad gets a good response from chemo and tolerates it well, then maintenance would certainly be an option to consider. Anything that is effective and could be well-tolerated over an extended period is a good candidate for maintenance, leaving newer generation EGFR inhibitors for later, if necessary.

Good luck with whatever option is chosen.

JimC
Forum moderator

I imagine that is only this particular trial. No one knows why some people do well and others don't. They maybe guessing that someone with just one mutation (EGFR) won't have the same benefit from the pd-1 drug as someone with a more complicated mutation profile. That way the trial will have higher efficacy rate if their guess is true. This idea has been discussed a bit in our Immunotherapy Patient Forum video collection (they can be found on the right column of this page)

Best of luck,
Janine

Hi Fischer,

I'm so glad your dad has responded so well. Congratulations and my it be long long lasting!

All trials are different and actually some of the standards are changing so I'd not presume a standard in a case like yours. So it's a question only the trialists on his case can answer. Cancer trialists are usually very good at fielding questions, concerns and needs of there patients so don't hesitate to ask.

Let us know how it goes.

Janine