Treatment Options

Portal Forums Lung/Thoracic Cancer EGFR Inhibitors Treatment Options

This topic contains 36 replies, has 4 voices, and was last updated by  cc1990 1 month, 2 weeks ago.

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June 25, 2017 at 9:59 am  #1290903    

cc1990

Thanking you in advance for this site!

My husband ‘s mutation is presently: EGFR L858R (exon 21). He has been stable both brain and chest down. He did have SBRT to primary lung mass and SBRT to a liver met.

Present Treatment: Tagrisso @ 40 mg for brain mets and Alimta Maintenance (Cycle 7). He is also managing side-effects fairly well, just has the fatigue, but still manages to go to the gym 2 x per week except for right after chemo..

TREATMENTS THUS FAR:
Nov. 2013….. 1 x carboplatin/alimta, then started Tarceva
Dec. 2013-June 2015…..Tarceva
June 2015…. Biopsy showed T790M, started Clovis Trial; could not tolerate side-effects
Dec. 2015….. Started Tagrisso
May. 2016….. Started progressing on Tagrisso
Sept. 2016…. Biopsy showed T790M dropped
Sept. 2016…. Started carboplatin/alimta + Tagrisso

Question #1: When current treatment fails are there other treatments available besides immunotherapy?

Question #2: Is it possible to go back on Tarceva?

Question #3: What line of treatment thus far as he had (is it considered 3)?

Thanks again for any input you can provide!

June 25, 2017 at 10:49 am  #1290904    
JimC Forum Moderator
JimC Forum Moderator

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


Jul 2008 Wife Liz (51/never smoker) Dx Stage IV NSCLC EGFR exon 19
4 cycles Carbo/alimta, 65% shrinkage
Tarceva maintenance
Mar 2010 progression, added Alimta, stable
Sep 2010 multiple brain mets, WBR
Oct 2010 large pericardial effusion, tamponade
Jan 2011 progression, start abraxane
Jun 2011-New liver, brain mets, add Tarceva
Oct 2011-Dx Leptomeningeal carcinomatosis; pulsed Tarceva
At rest Nov 4 2011
Since then: http://cancergrace.org/blog/jim-and-lisa

June 25, 2017 at 12:05 pm  #1290905    
catdander forum moderator
catdander 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

June 25, 2017 at 12:17 pm  #1290906    
catdander forum moderator
catdander forum moderator

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

July 1, 2017 at 12:21 pm  #1290965    

cc1990

Thank you JimC and catdander!

My main concern with the next treatment is being able to stay on Tagrisso as he has remained stable in the brain. The oncologist did say that the next treatment he would have to stop the Tagrisso since it would interact with whatever he had in mind… and, this concerns me as we are trying to avoid WBR as long as possible, it would have to a Hail Mary for WBR!

July 1, 2017 at 3:34 pm  #1290972    
catdander forum moderator
catdander forum moderator

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

July 8, 2017 at 8:22 am  #1291027    

cc1990

Regarding Janine’s post above:

“I understand wanting to plan ahead and circumvent possible problems however it’s likely that the most pressing issues will command the treatment planning”

Perfectly said…

We have a problem right now with my husband’s creatinine level which has increased from 0.94 (collected on 6/22/17) to 1.35 (collected on 6/29/17)… first time it has jumped (diagnosed in 2013).

He’s going on Cycle 8 of Alimta Maintenance (next chemo is July 13). He’s also taking Tagrisso for brain mets. He also gets a shot of Xgeva. We are hoping it’s a lab error or just because he’s not drinking enough water… that would be a simple explanation.

1. What is the standard of care if creatinine level jumps and has stable disease?

2. Also, he is due for an MRI of the brain with contrast… would they do it without the contrast?

I appreciate all your thoughts regarding this issue.

Kate

July 8, 2017 at 9:50 am  #1291028    
JimC Forum Moderator
JimC Forum Moderator

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#post-1252636

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


Jul 2008 Wife Liz (51/never smoker) Dx Stage IV NSCLC EGFR exon 19
4 cycles Carbo/alimta, 65% shrinkage
Tarceva maintenance
Mar 2010 progression, added Alimta, stable
Sep 2010 multiple brain mets, WBR
Oct 2010 large pericardial effusion, tamponade
Jan 2011 progression, start abraxane
Jun 2011-New liver, brain mets, add Tarceva
Oct 2011-Dx Leptomeningeal carcinomatosis; pulsed Tarceva
At rest Nov 4 2011
Since then: http://cancergrace.org/blog/jim-and-lisa

August 2, 2017 at 1:06 pm  #1291177    

cc1990

Thanking you in advance and I will add you’ve been “spot on”. Regarding the CR level the oncologist was not concerned.

Our newest development is that there is possible progression, in the bones due to my husband having some pain, but oncologist is not sure if cancer so need to study it more and progression in chest area. So basically the Alimta has been stopped and the Tagrisso is continued until another chemo will be started in about 3-4 weeks. We were concerned about the brain if Tagrisso was stopped.

We’ve decided to get a 2nd opinion at another cancer center which is Tuesday. A Guardant blood test was done. Also, the oncologist said a bronchoscopy is not needed only if we wanted to get that. There is one caveat there might not be enough tissue.

His oncologist’s opinion is to go on a treatment that we know would work (which he’s thinking another chemo). He feels you keep the trials for later. Is chemo after Alimta stronger than Alimta (they had said Alimta was the mild chemo)?

What is your opinion as far as whether to do chemo or if offered to do a trial? My thinking is that there is a trial where we will be going for a 2nd opinion which is Navitoclax and Tagrisso and since he’s already on Tagrisso I’m thinking this might work, but of course I’m nonclinical so don’t really know.

Kate

August 2, 2017 at 5:32 pm  #1291178    
catdander forum moderator
catdander 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

September 1, 2017 at 7:07 pm  #1291355    

cc1990

Hi Everyone:

What exactly does “NF1 loss” mean on Guardant blood test?

Kate

September 2, 2017 at 8:44 am  #1291357    
JimC Forum Moderator
JimC Forum Moderator

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


Jul 2008 Wife Liz (51/never smoker) Dx Stage IV NSCLC EGFR exon 19
4 cycles Carbo/alimta, 65% shrinkage
Tarceva maintenance
Mar 2010 progression, added Alimta, stable
Sep 2010 multiple brain mets, WBR
Oct 2010 large pericardial effusion, tamponade
Jan 2011 progression, start abraxane
Jun 2011-New liver, brain mets, add Tarceva
Oct 2011-Dx Leptomeningeal carcinomatosis; pulsed Tarceva
At rest Nov 4 2011
Since then: http://cancergrace.org/blog/jim-and-lisa

September 2, 2017 at 9:15 am  #1291362    
JimC Forum Moderator
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/Lanman.pdf

JimC
Forum moderator


Jul 2008 Wife Liz (51/never smoker) Dx Stage IV NSCLC EGFR exon 19
4 cycles Carbo/alimta, 65% shrinkage
Tarceva maintenance
Mar 2010 progression, added Alimta, stable
Sep 2010 multiple brain mets, WBR
Oct 2010 large pericardial effusion, tamponade
Jan 2011 progression, start abraxane
Jun 2011-New liver, brain mets, add Tarceva
Oct 2011-Dx Leptomeningeal carcinomatosis; pulsed Tarceva
At rest Nov 4 2011
Since then: http://cancergrace.org/blog/jim-and-lisa

September 2, 2017 at 12:55 pm  #1291367    
catdander forum moderator
catdander 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&cond=nsclc&rank=1#contacts

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

September 13, 2017 at 8:09 pm  #1292389    

cc1990

First of all, thank you both for the info regarding NF1 loss.

We were about to enter a trial starting Friday, 9/15, Tarceva + trametinib. However, a biopsy was performed on Monday on a lymph node that was lighting up on a PET scan. The biopsy now showed cells that were SCLC. The trial was canceled and the trial oncologist said to go back to the regular oncologist for chemo. BTW, if it were not for this trial, he would never have known this as his regular oncologist was not going to do a tissue biopsy; however, we pushed for it, it just so happened that the trial did the biopsy.

The trial oncologist did say that the next chemo could knock it out and then another mutation may be found.

Also, it’s not acting like SCLC as he’s had slow progression. He’s not had treatment since August 1st.

My question: where does he go from here.., what chemo is offered? Would this be considered “extensive” or “limited”?

Kate

September 14, 2017 at 11:32 am  #1292393    
catdander forum moderator
catdander forum moderator

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

September 14, 2017 at 11:49 am  #1292394    

cc1990

Thank you, Janine.

We just clarified with the oncologist that he is still EGFR+, but has large cell/small cell mix with neuro-endocrine features. From what that sounds like it doesn’t sound good… does it? What a shocker!

Right now he is not on any chemo, but was on Alimta Maintenance until July.

Chemo this time will be carboplatin and etoposide. If he had carboplatin last year (x 4), can that be used again?

Also, she did mention that the chemo could morph into something else… have you heard this before?

Kate

September 15, 2017 at 7:59 am  #1292400    
JimC Forum Moderator
JimC Forum Moderator

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


Jul 2008 Wife Liz (51/never smoker) Dx Stage IV NSCLC EGFR exon 19
4 cycles Carbo/alimta, 65% shrinkage
Tarceva maintenance
Mar 2010 progression, added Alimta, stable
Sep 2010 multiple brain mets, WBR
Oct 2010 large pericardial effusion, tamponade
Jan 2011 progression, start abraxane
Jun 2011-New liver, brain mets, add Tarceva
Oct 2011-Dx Leptomeningeal carcinomatosis; pulsed Tarceva
At rest Nov 4 2011
Since then: http://cancergrace.org/blog/jim-and-lisa

September 15, 2017 at 8:11 am  #1292401    
JimC Forum Moderator
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


Jul 2008 Wife Liz (51/never smoker) Dx Stage IV NSCLC EGFR exon 19
4 cycles Carbo/alimta, 65% shrinkage
Tarceva maintenance
Mar 2010 progression, added Alimta, stable
Sep 2010 multiple brain mets, WBR
Oct 2010 large pericardial effusion, tamponade
Jan 2011 progression, start abraxane
Jun 2011-New liver, brain mets, add Tarceva
Oct 2011-Dx Leptomeningeal carcinomatosis; pulsed Tarceva
At rest Nov 4 2011
Since then: http://cancergrace.org/blog/jim-and-lisa

September 15, 2017 at 9:32 am  #1292402    

cc1990

Thanks, Jim, for the info. I think the one to three percent of the transformation probably is a little higher now (just my opinion) as people are living longer with lung cancer and are on these TKI’s.

We had asked the oncologist whether he could get into a trial or immunotherapy, she said he would not qualify due to the “mix” (meaning EGFR+, large cell/small cell mix with neuro-endocrine features). Isn’t small cell the same as neuro-endocrine? What is large cell?

Also, for this chemo regimen, carboplatin/etoposide… how long is this treatment, indefinite, or to see if it suppresses the small cell?

Kate

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