KRAS adeno options - 1266168

Hello phillydaughter,

I'm sorry to hear of your Mom's diagnosis, but I hope that we can provide some information that will help you and her. I have quoted your profile information below, but you may want to add it to your forum signature. Just click on your name next to your post, then click on "Edit Bio & Forum Signature". Scroll down to the signature section and fill in your Mom's information there. Then be sure to scroll to the very bottom of the page to save the information. Once you've done this, her history will appear on each of your posts, which will help us better answer future questions you post.

History: Mom: 70 yrs old, social smoker who quit approx 30 yrs ago. Back pains July 2014, fracture and suspicious area in spine on MRI, 2nd biopsy confined lung adeno (Aug 2014), Aug 2014 MRI - Lesion on spine grew and 2nd lesion(iliac) radiated (early Sept) one large dose (8Gy). Brain MRI - 2mm and 3mm lesion on brain lots pain weak since sedentary. started morphine EGFR neg. KRAS (65%) pos & p53 (55%)pos. End Sept started Carbo/Alimta

First, radiation will kill cancer cells to which it's targeted, and that often relieves pain. Once there is a fracture though, damage has been done and eradicating the cancer cells will not heal the fractured bone, so other interventions may be necessary.

Currently there are approved targeted agents for a couple of NSCLC mutations, but such patients represent only a small percentage of the total NSCLC population. But research into agents targeting KRAS continues, as you can see in this presentation: http://cancergrace.org/lung/2013/01/26/is-there-a-new-promising-option-…

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I don't understand what your Mom's oncologist was thinking when she said there is no second line treatments or trials. There most certainly are, and if your Mom's cancer begins to progress after first line treatment, not only will currently approved second line NSCLC drugs such as Docetaxel and Tarceva be available, but there are other standard drugs and trials which could be used.

Avastin is a drug which may or may not provide a benefit when added to a chemo doublet; the trial evidence is limited. It may have been withheld because of your Mom's brain mets, which from your signature do not appear to have been treated. In that regard, although chemotherapy can successfully treat brain metastases, it may not penetrate the blood-brain barrier well enough to do so effectively, and if those mets progress, radiation would be the favored treatment.

Good luck with your Mom's treatment, and please let us know if you have further questions.

JimC
Forum moderator

Trials take years to be completed, so there is no further information to offer about selumetinib -- the phase 3 trial that was initiated based on the encouraging phase II results is ongoing now and widely available at many sites around the world. Here's more information:

http://clinicaltrials.gov/ct2/show/NCT01750281?term=SELECT-2+selumetini…

Nintedanib is the subject of a similar trial that is being done now.

And ramucirumab did come out with a statistically significant but overall rather modest (<2 month) improvement in overall survival. It is approved for gastric cancer but not for lung cancer and at this time is rrely if ever used for lung cancer.

There are absolutely clinical trials out there, so maybe the issue/answer was that her oncologist doesn't have clinical trials available for her at his site. If you'd like, perhaps it would be helpful to seek a second opinion at an academic center or larger cancer center, where a wider array of clinical trial options may be available.

Good luck.

-Dr. West

Normally when brain metastases are discovered, the thought is to treat them as soon as possible to avoid some of the difficult symptoms that growing brain mets can cause. In your Mom's case, the mets are small in size and number and if it is not felt that they are causing symptoms, waiting to see the effect of the first line treatment she just began, keeping a close eye on symptoms. One of the advantages of this approach is that chemo is normally withheld during brain radiation, so waiting and watching would not require interrupting her chemo.

As far as the bone met, it is difficult to say much without full knowledge of her medical information and scans, so it's something that should be discussed with both her radiation oncologist and medical oncologist, perhaps in an expedited fashion. It is possible that there is bone damage that is not remedied by killing the cancer cells, or it may be that she needs a longer course of radiation. In any event, addressing the pain with medication should be discussed if it hasn't been already, or if current medications/dosages are not currently effective.

Here is a discussion of radiation treatment for bone mets: http://cancergrace.org/lung/2007/02/18/treating-bone-mets-focus-on-radi…

JimC
Forum moderator

I would add that for a couple of small brain lesions, these could potentially and would very often be treated with stereotactic radiosurgery on a single day, which could potentially be done on a non-chemo day and not necessarily interrupt chemotherapy. It would be very appropraite to get in at least a couple of cycles of chemo before trying to determine whether it's helping or not.

As for the radiation to bone, not every patient achieves pain relief from radiation, and she's getting chemotherapy now that can potentially treat this. It may be feasible and potentially helpful to do further radiation, but it's possible that there isn't an intervention other than escalating pain medication that will significantly improve pain control.

Good luck.

-Dr. West

Phillydaughter, I'm so sorry your mom is having this bump in the road. I hope heparin gets rid of the clots and she is able to move forward with chem. I imagine the reason for not giving chemo is the doctors want to get the clots and oxygen under control before putting her in jeopardy of having more. I know how difficult it is to have a loved one in that position though I hope you can take comfort in knowing her most immediate needs are being taken care of.

Please let us know what is found from the mri s and plans to manage the pain.

Hoping for the best,
Janine

Hi phillydaughter,

I would also add that it is not unusual for a chemo treatment to be delayed a week or two due to low blood counts or other side effects of treatment, without an adverse effect. There is nothing particularly magical about the typical three-week cycle except that for most patients the low blood counts caused by the previous treatment tend to have resolved over that period of time.

Also, it's likely that the abdominal injection your Mom is receiving is lovenox, which tends to be very effective in preventing blood clots.

JimC
Forum moderator

Blood clots such as these are not uncommon, and they can usually be treated effectively with blood thinners such as the lovenox (enoxaparin) injections she's receiving.

Indeed, it's not unusual to delay for long enough to settle more acute issues before giving outpatient chemo. A delay of a week or two is very unlikely to be detrimental, but rushing to deliver chemo while other issues are going on may lead to problems.

I hope she's doing better soon.

-Dr. West

Wife,64 no smoker, stage IV adenocarcinoma of left lung with no EGFR, ALK mutations but identified KRAS mutation has option to stage II clinical trial of PD L1 with three week wait to identify If she qualifies or would you advise starting standard carboplatin/pemextred chemo. Would this preclude subsequent Mec inhibitor trials?

Phillydaughter,

No, what you're describing doesn't sound so much like leptomeningeal spread. Perhaps just some compression of a nerve by cancer, which is quite common and more treatable. Admittedly, however, I don't have the details, but I wouldn't conclude based on so little information that she has leptomeningeal carcinomatosis.

Coachwilson17,

We can't provide a recommendation of what someone who isn't our patient should do. The conventional treatment is standard chemotherapy, with a response rate of about 25-35% (significant tumor shrinkage), and a higher proportion (more like 70-75%) demonstrating at least stable disease and likely benefiting some.

Immune checkpoint inhibitor therapies (anti-PD1 or anti-PD-L1) don't yet have an established role and can't yet be said to be superior to conventional chemotherapy. My impression, shared by many experts in the field, is that they are very effective for a minority of patients, likely 15-20%, but not especially helpful for the other patients. If patients are identified as having significant PD-L1 expression (which may be part of the delay in enrolling on the trial), the response rates are typically higher, and in that population, the probabilty of benefit may be higher than that of chemotherapy. However, for an unselected population (not screened for PD-L1 expression), there is little reason to think that immunotherapy will be helpful for more people than standard chemotherapy, even if it may be a better treatment if you happen to be in the minority who will benefit.

Another factor is how quickly the cancer is progressing. A patient without cancer symptoms and who is generally healthy can more safely afford to wait a few weeks to start treatment, while someone losing weight and sick from cancer may well be much sicker if they wait 3-4 weeks or longer before actually starting treatment.

Good luck.

-Dr. West

Hi phillydaughter,

Chemo is typically withheld during radiation because it can act as a radiosensitizer, effectively increasing the radiation dosage to an unpredictable degree, in addition to intensifying the side effects of that radiation.

JimC
Forum moderator

xgeva can cause bone pain so may be adding to your mom's problems. It's also possible that it is as effective in fewer doses so stopping it may only be beneficial.

Janine

I don't know where you or your mom is but fyi, Grace is having a patient forum on immunotherapies in Chicago next weekend. It is sure to be very helpful in acquiring more knowledge. Here's the post, http://www.jotformpro.com/form/42266827790969 https://docs.google.com/document/d/1ih75jS0VuZXm2Jqt-E5BbeqG6-fyZbwJly7…

There is actually no good evidence that it's necessary to give XGEVA (denosumab) as frequently as every 4 weeks, and plenty of oncologists, including myself, regularly favor having patients get XGEVA every 6-12 weeks and seem to do just as well. There is reason to have some concern about cumulative toxicity from these agents over time, so more often is not necessarily better, and the companies making these drugs aren't really interested in doing studies to show that you can do as well or better with less frequent treatment.

And yes, we typically prefer to hold chemo with a short course of radiation.

Good luck.

-Dr. West