T790M mutation gone , but original EGFR exon 19 unchanged with Tagrisso - 1288931

Hi Kempten,

I think the initial question would be: how slight is the progression in the lung mass compared to it's overall size? Has there been any thought to continuing Tagrisso for a bit to confirm progression and determine the rate of growth? Dr. West has often stated that it often makes sense to stay with a well-tolerated treatment even in the face of slow progression, as "bad brakes are better than no brakes." Of course your local doctors are best able to judge that question.

If the original percentage of exon 19 mutation is unchanged, that seems to indicate that it is not only the exon 19-positive portion of the cancer which is progressing, since you would expect the percentage to rise. Either way it's just speculation, since unfortunately we don't understand resistance and progression all that well yet.

There has been some discussion of treating with Tarceva after the failure of Tagrisso, but that's after using Tagrisso in a first-line setting. Even in that context, there isn't good evidence yet for its efficacy, as Dr. Ramalingam stated just two months ago:

“Tagrisso is being studied in the first line therapy setting to see if shutting down the T790 escape (resistance) mechanism pro-actively will improve the outcome for patients. The approach has shown promising early results and are now being studied in a large clinical trial. This trial compares tagrisso directly with tarceva or iressa. We are still learning about what mechanisms of resistance are observed when patients are treated with tagrisso in the first line setting. It is possible that for a subset of these patients, using iressa or tarceva after they have received tagrisso might be beneficial, but it is too early at this time to make firm statements on this issue.The presently available data are based on laboratory experiments and have not been confirmed in patients” - http://cancergrace.org/topic/tagrisso-first-line-and-then-tarceva-thera…

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Dr. West also expresses doubt about the efficacy of first and second generation TKIs after Tagrisso failures here.

If there are no actionable mutations shown, then the primary options would most likely be standard chemotherapy regimens, to which EGFR mutation positive patients tend to respond well. Immunotherapy is an option, but the response rates for this group of patients tends to be low.

Good luck with whichever treatment path is chosen.

JimC
Forum moderator

Kemptem,

Actually there is changing thought on "weeding the garden" as Dr. Weiss calls it. For those who show oligoprogression (one or 2 site of progression) studies are showing longer periods of efficacy on tki drugs such as those for egfr and alk mutations in lung cancer. Dr. Weiss has been a proponent of these studies from the beginning and he talks about it in the link below. I would think if the cancer bulk is causing problems the threshold for trying this is even lower. Of course your care team is in the best place to determine this but the work is out there for its use.

http://cancergrace.org/lung/tag/oligoprogression/

As for immunotherapy for those without much pd-l1 connection there is hope that there's still chance for efficacy with these new immunotherapy drugs and yes combining them with other drugs is one of the ways clinical researchers are trying to make immunotherapy drugs effective for those without pd-l1 in their tumors. This is still in trials. If you're able to join a trial of this sort, that would mean they are hopeful your immune disease won't be a problem and if so they will be able to manage it. As has been pointed out the best care comes from being on a trial; it's built into the science.

Best hopes,
Janine

Kemptem,

Actually there is changing thought on "weeding the garden" as Dr. Weiss calls it. For those who show oligoprogression (one or 2 site of progression) studies are showing longer periods of efficacy on tki drugs such as those for egfr and alk mutations in lung cancer. Dr. Weiss has been a proponent of these studies from the beginning and he talks about it in the link below. I would think if the cancer bulk is causing problems the threshold for trying this is even lower. Of course your care team is in the best position to determine this but the work is out there for its use.

http://cancergrace.org/lung/tag/oligoprogression/

As for immunotherapy for those without much pd-l1 connection there is hope that there's still chance for efficacy with these new immunotherapy drugs and yes combining them with other drugs is one of the ways clinical researchers are trying to make immunotherapy drugs effective for those without pd-l1 in their tumors. This is still in trials. If you're able to join a trial of this sort, that would mean they are hopeful your immune disease won't be a problem and if so they will be able to manage it. As has been pointed out the best care comes from being on a trial; it's built into the science.

Best hopes,
Janine

Hi Kempten,

Given your circumstances, I can understand your concern about immunotherapy, especially given its response rate among EGFR-positive patients. Although autoimmune disease is often well-controlled with immunotherapy, it is a complicating factor which could very reasonably sway your decision.

In general, the response rate among all immunotherapy patients is lower than we would like, which is why combination therapies are being studied. So far, there is enthusiasm but not necessarily compelling data for those combinations.

As you say, radiation (other than to palliate symptoms such as bone pain) is not ordinarily chosen in the metastatic setting, although as I'm sure you've read here, local treatment of oligometastases has gained some favor. In your situation though, you're considering radiating the primary lung tumor. Not only does that fail to address any micrometastases in the remainder of the body, but chest radiation can be debilitating, and may require cessation of your systemic therapy during the radiation therapy. One of the main reasons local therapy tends not to be favored is that it can knock you down enough that you may not be ready to tolerate systemic therapy when you need it.

JimC
Forum moderator