Treatment Options - 1290903

Hi cc1990,

It's good to hear that the chemo/Tagrisso combination appears to be working well and remains tolerable for the most part.

Immunotherapy would not usually be the first choice for an EGFR+ patient, since PD-L1 expression is usually not high and response rates tend to be low. Of course, there are always exceptions, so if PD-L1 testing can be done, immunotherapy might prove to be an option.

It would be unusual to return to Tarceva after clear evidence of progression but again, if testing shows that the T790M is no longer present, it could be tried. On the other hand, a biopsy/test result only provides a snapshot of the particular tissue tested, which may not be representative of all the cancer cells present in the body.

The first choice as a subsequent line of therapy would probably be a standard chemotherapy agent. As a second or later line of therapy, Taxotere (Docetaxel) is the best-studied and is proven effective, but other agents such as Taxol, Abraxane, Gemzar and Navelbine can also be used.

Clinical trials of agents with novel mechanisms of action could also be utilized. You might want to discuss those with the oncologist; if your husband's doctor does not have suggestions, then a second opinion with an oncologist at a major teaching hospital might be a good idea, since they tend to be aware of most of the new agents in the pipeline.

Different trials may vary in how they determine the number of previous lines of therapy, but three or four would be likely.

Continued best wishes with the current regimen.

JimC
Forum moderator

Hi cc1990,

Welcome to Grace we are happy you're here though of course never happy to know you must be here. I know how glad you are to have your husband active at 3 1/2 years after diagnosis.

It's difficult to say what line of treatment he's on and usually it only matters if there is an exclusion/inclusion rule to a trial that would apply. In that case the intake oncologist for a trial would probably have some leeway to argue for or against a particular number. first line would def be the chemo doublet, but is 2nd line tarceva or can you say it's not because it was used as maintenance. Then do you say tagrisso alone is a separate line than tagrisso with carbo/alimta added. I can see a good argument for 5 lines (1chemo doublet, 2tarceva, 3clovis trial, 4tagrisso, 5chemo added. Or you could argue down to 3 lines.

Usually oncologists like to exhaust a treatment before moving on but there are times when moving back to a treatment is helpful. Alimta is a good example of that where many people stop because of side effects or moving to a tki that can be taken orally and having good efficacy. There is no data to suggest moving back to 1st gen tki shows efficacy, though I don't think the question has been asked in a situation where the t790m mutation has lessened or disappeared. It would definitely be a discussion to have with your husband's oncologist.

There are many drugs in development and drugs that have been approved for other types of cancer that target specific mutations. Mutation testing is becoming more efficient. Some tests are quite accurate and fast at looking for one specific mutation. Others test for many mutations but may not be as accurate at picking up all the mutations targeted. With all the promise of these targeted drugs there are many clinical trials that may be options when the time comes. However it is probably best to wait until there is progression to test for other mutations for a couple of reasons.
contd

Jim replied while I was called to lunch but I'll let my previous post stand and finish up here.

...However it is probably best to wait until there is progression to test for other mutations for a couple of reasons. The first is any mutation that may be found to have a targeted treatment may not be developed in his body the 2nd reason to wait is the mutation being targeted may not have a treatment developed. So waiting until the time it's needed would allow for either of these eventualities. However mutation testing does take some time to process so it's a catch 22, wait until you need it but not so long that waiting for results isn't an option. Like Jim suggested a 2nd opinion goes a long way in a situation where an oncologist may be perfectly able to treat but doesn't have the base to know what's new in the pipeline.

I hope we here good things to come.
All best,
Janine

I understand wanting to plan ahead and circumvent possible problems however it's likely that the most pressing issues will command the treatment planning. There are active clinical trials testing combos with tagrisso that may be options when the time comes or maybe even some answers to the questions of whether adding additional drugs to tagrisso are helpful, hurtful or neither. In a trial setting the patient is monitored closely to catch any adverse events that may happen but taking the same combos outside a trial setting would leave the patient without the added safety net. We just don't have answers to what one can expect when combining already toxic drugs unless they are clinically tested. This is a tough row to hoe. (excuse the euphemism my next door neighbors are landscaping)

Hoping for the best,
Janine

Hi Kate,

I'm sorry to hear of this latest issue. It's not uncommon for Alimta to cause creatinine levels to rise. Clinical trials have been know to limit admission to patients with levels below 1.9, so your husband's level probably isn't so high as to prevent further treatment. It's just one reading, so most important now would be to keep an eye on it to see if the trend continues. Dr. Pietanza commented on this issue, in the context of an even higher level:

"I have seen irreversible kidney damage from pemetrexed, especially when it has been given for a prolonged amount of time. In general, we do not like to give the drug if the patient has an abnormal creatinine. Further, it is not about the level of the creatinine, but about the “creatinine clearance”, if this number goes to 45 or lower, then the drug cannot be cleared from the blood and there will be too many side effects from the drug – leading to mouth sores and a decrease in all of the blood counts. It does seem that [the original poster's] disease is under good control and we don't want to expose her to the potential risks of chemotherapy. Thus, now does seem to be a good time for a treatment break. She will need normal kidneys later for other chemotherapies or for clinical trials. Sometimes, the creatinine improves." - http://cancergrace.org/topic/max-creatinine-level-for-continued-chemo#p…

If there is reduced kidney function, MRI can be performed without contrast. As Dr. Pinder has written:

"MRI can be performed with or without gadolinium contrast. By adding contrast, it is easier to detect areas of inflammation, small tumors and multiple sclerosis lesions. Contrast makes brain MRI more sensitive for detection of meningeal carcinomatosis.

For the purposes of detecting brain metastases, contrast CT, MRI and/or MRI with gadolinium contrast are all useful for looking at the brain." - http://cancergrace.org/forums/index.php?topic=5180.msg32090#msg32090

JimC
Forum moderator

Hi Kate,

I'm so sorry your husband has progressed on alimta. Alimta isn't known as mild because it's not as effective, it's known as being mild because the side effects seem to be milder than others. There are several other chemo drugs that may have efficacy after moving from alimta. Usually as one chemo drug follows another the efficacy diminishes.

A second opinion is never a bad idea. A lung cancer specialist who participates in clinical trials will be able to point you in the right direction for possible appropriate trials. I ass,u.me the oncologist's thinking behind waiting on a trial is that treatments in trial don't have proven efficacy. The other side of that is that the proven options aren't especially bright and there is a lot of promise of new treatments coming down the pike. Another thought is that there are exclusion criteria in each clinical trial that sometimes include certain past treatments and usually symptomatic brain mets.

Treatment decisions are very individual at this point without obvious best choices. Even personal preference about how your husband wants to live is very important.

I hope your husband does well with whatever he chooses to do next.
All best,
Janine

Hi Katie,

NF1 is a genetic mutation which can be associated with acquired resistance, although there doesn't seem to be a great deal of research being done in the context of lung cancer, most likely because it's not seen nearly as frequently as T790M, for example.

JimC
Forum moderator

Katie,

Here's a chart which details just how infrequently NF1 plays a role in acquired resistance: https://cdp.cancer.gov/resources/technology_development_resources/ctdna…

JimC
Forum moderator

Hi cc1990,

There does appear to be one clinical trial that hasn't yet begun to recruit participants at UC San Francisco.
A long shot I know. Here are the details, https://clinicaltrials.gov/ct2/show/study/NCT03232892?term=nf1+mutation…

I hope your husband is feeling alright and y'all are able to live life a bit outside the cancer realm .
All best,
Janine

Hi Kate,

I'm sorry your husband is facing new challenges to be sure it's the nature of the beast. I don't think it's helpful to get caught up in labeling the cancer especially since he's likely to have similar chemo options. It's not really known if this is a new phenomenon or that nsclc has been changing to sclc but without repeat biopsies it's not been caught. Extensive stage sclc is equal to stage IV and limited sclc to stages I-III nsclc. There are more nuanced choices in nsclc than sclc that make the difference in the number of stages. Too it's not understood if all or part of the cancer has changed.

If your husband is still on the platinum doublet they may want to exchange alimta (which doesn't show much efficacy in sclc) with another drug such as Etoposide or Irinotecan both of which have efficacy in nsclc and sclc. Both drugs also have efficacy given individually if the platinum has been used to 4-6 cycles.

I hope he does well with the plan.

All best,
Janine

Hi Kate,

I'm sorry to hear about the changed histology and yes, there have been cases of EGFR+ lung cancer turning into other forms, especially small cell.

Usually after first-line combination therapy the platinum agent is dropped, due to the possibility of added toxicity, particularly a decrease in bone marrow function. But if it has been a while since it was used, at times it makes sense to return to it to gain the added benefit it can provide when used in combination with another agent.

I hope the new combination works very well.

JimC
Forum moderator

Hi Kate,

It took me a while to find it, but here's what Dr. West had to say about such a transformation:

"What we learn from a biopsy really is two-fold. The first, and easiest part, is the pathologist looks at it under the microscope and says, “is this still non-small cell lung cancer, or is this changed?” A relatively rare phenomenon is transformation of non-small cell lung cancer into small cell lung cancer — it happens maybe one to three percent of the time, but it’s a relevant thing to find, and we would adjust chemotherapy as a consequence of this." - http://cancergrace.org/lung/tag/epidermal-growth-factor-receptor/

JimC
Forum moderator

Hi Kate,

Small cell and large cell are part of a continuum of Neuro-endocrine cancers. Dr. West describes that continuum here: http://cancergrace.org/lung/files/2010/01/horton-pt-2-neuroendo-lung-tu…

Normally the carbo/etoposide regimen is used for 4-6 cycles, then treatment is stopped, depending on the results. In any event, the platinum component is usually not continued.

JimC
Forum moderator

Dr. West explains large cell and small cell neuroendocrine lung cancers, "One of the less common subtypes of non-small cell lung cancer is known as large cell neuroendocrine, and it is in the same family as small cell lung cancer — these are all known as neuroendocrine cancers. They originate from cells that are in the middle of the body, in the middle of the chest, that have evolved to have hormone-secreting abilities. Because of that, large cell neuroendocrine and small cell lung cancer really share enough features that they are treated in a very similar way." Dr. West goes on to discuss how these 2 lung cancers are treated similarly. http://cancergrace.org/lung/2016/04/19/gcvl_lu_histology_specific_recom…

In the following post Dr West explains why treatment using platinum is only used 4 to 6 treatment.

"With carboplatin, cumulative cytopenias (low blood cell counts) and a rapidly escalating risk of a severe and potentially dangerous hypersensitivity reaction (which can also occur with ongoing cisplatin but is notorious and almost inevitable with carboplatin) make indefinite carboplatin too challenging and inadvisable." http://cancergrace.org/lung/2011/12/24/beyond-4-cycles-1st-line/

Hi Kate,

A "cycle" refers to each treatment and the off-weeks following it. Typical is a three week cycle, in which the chemo infusion is given on day one, with the next one three weeks later. That allows time for blood counts to recover and side effects to fade.

JimC
Forum moderator

If taking one chemo drug the infusion would be once a cycle. For a platinum doublet like carbo/etoposide a cycle usually consist of 3 infusions in week one for a 3 week cycle or even 1 infusion a week for 3 weeks in a 4 week cycle. An example from the macmillan is below. Note that this is from a UK site and I don't think capsules are used much or at all in the U.S. Otherwise this is a pretty typical schedule.

"Your course of carboplatin and etoposide
You have chemotherapy as a course of several sessions (or cycles) of treatment over a few months. Carboplatin and etoposide chemotherapy can be given in different ways. Your doctor or nurse will be able to give you details of your individual treatment course.

Here is a description of one method of treatment:

Each cycle of carboplatin and etoposide takes 21 days (three weeks).

On day 1 you have carboplatin and etoposide. Both drugs are given as a drip.
On day 2 you will have either an infusion of etoposide or you will be given
etoposide capsules.
On day 3 you have an etoposide drip or capsules. The capsules are taken twice a day." http://www.macmillan.org.uk/cancerinformation/cancertreatment/treatment…

Hi Kate,

A biopsy is a snapshot of the cancer in the area that has been sampled, and may or may not be representative of the cancer in the rest of the body. Carbo/etoposide is a regimen that is effective in both NSCLC and small/large cell lung cancer, so you would hope to be treating the cancer throughout the body. Usually, in the stage IV setting radiation is not used except to reduce symptoms (such as pain from bone mets) and for brain mets. Exceptions may be made in instances where there is only one or two areas of metastasis.

"The AP window is the space between where the aorta turns around and the pulmonary artery. There are lymph nodes here that can be involved in lung cancer or lymphoma." - http://cancergrace.org/forums/index.php?topic=4942.msg30180#msg30180

You would probably look for SCLC trials, then check to see if this particular combination qualifies for entry.

JimC
Forum moderator

As a new member, I am amazed what I have already! Thank you!

My husband was diagnosed in November 2014 with Stage 4 NSCLC . He has had numerous treatments in the past two and a half years. He has been on Tagrisso with some progression so in June, his oncologist added Avastin every three weeks. He has increasing bone metastasis and severe pain. The oncologist has now added Alimta to the mix, also every third week. He has only had one dose of the Alimta and is having severe undesirable side effects.

Has anyone taken this combination of drugs?

Thank you,
Jeanned

Hi jeanned,

Welcome to GRACE. I'm sorry to hear of your husband's progression and symptoms. I'm sure that other oncologists have experimented with similar combinations, but at this point there isn't strong evidence of its efficacy. That's not to say it's a bad choice; all three drugs are approved for and show activity in lung cancer.

When side effects of treatment become burdensome, oncologists often consider dose reductions and/or discontinuing one or more drugs in a combination. If progression under Tagrisso was significant, that might be stopped or the dose reduced. If not, Avastin might be the one which is contributing the least.

Also, your husband's doctor could evaluate his side effects to see if it can be determined which drug is most contributing to those toxicities.

Finally, pain from bone mets can often be reduced with focal radiation to those metastases.

I hope your husband can find relief from his symptoms/side effects, and settle in on a treatment that effectively controls his cancer.

JimC
Forum moderator

Hi Kate,

I have not heard of that phenomena, but if a biopsy result suggested it, I would tend to think it might represent NSCLC cells that had not transformed into SCLC originally. Often a cancer is not homogeneous, especially when changes occur over time. As an example, an EGFR+ patient may develop T790M resistance, but that doesn't mean that all the cancer cells will bear that new mutation.

All that being said, the mantra is that cancer seems to be capable of anything.

JimC
Forum moderator

Hi Kate,

Etoposide is a fairly old drug researched as a doublet companion to a platinum drug. At that time treatment didn't normally go past the initial first line. So like most of the chemo drugs developed at that time research as a single agent is pretty scarce but oncologists do commonly use it with success for second line treatment or for those who are frail and can't handle platinum drugs. There is one study I found after a quick search that tests oral etoposide. https://www.ncbi.nlm.nih.gov/pubmed/2154860

All best,
Janine

Hi Kate,

As we discussed earlier in this thread, lung cancer is often not completely homogeneous-there can be cancer cells of differing pathologies in the same patient. The sample which was tested may indicate small cell/large cell, but there may still be cancer cells in other locations that remain NSCLC and EGFR+. On the other hand those cells that have tested as small cell/large cell may have mutated from EGFR+ NSCLC, which explains the radiologist's recommendation for molecular testing.

Although mixed SCLC/NSCLC is not that uncommon, since the proportions and amount of spread of the components tends to dictate the treatment used, there don’t tend to be treatments specifically geared toward mixed SCLC. Often a treatment is chosen which tends to be effective against both. Dr. Pennell discusses treatment choices in this thread, and you can access a discussion of immunotherapy for SCLC patients here.

JimC
Forum moderator