Choosing Medicine for Mom with Exon 21 Mutations

Portal Forums Lung/Thoracic Cancer EGFR Inhibitors Choosing Medicine for Mom with Exon 21 Mutations

This topic contains 13 replies, has 3 voices, and was last updated by  blesswen 2 months, 2 weeks ago.

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August 30, 2017 at 12:33 pm  #1291339    

blesswen

My mother is just diagnosed with Adenocarcinoma stage 3b or 4(brain and bones clear, but no PET performed). She is Asian at her 80’s with EGFR exon 21 mutations. I am devastated since I just lost my father earlier this year. She is very frail and has heart disease and diabetes. We’re trying to determine the best treatment for her. We eliminated surgery and chemo and are choosing amongst Iressa (Gefitinib), Tarceva (Irlotinib), and Gilotrif (Afitinib).

We’re more prone to choose Tarceva with a lower dosage. Based on my limited research it seems Iressa is more toxic to the liver, more interstitial lung disease cases, and not good for elderly and people with heart disease. It seems Taceva’s side effect is more superficial other than GI problems. Has anybody had experience taking Iressa? Has anybody had interstitial lung disease or liver issues from taking Tarceva?

As for 2nd generation Gilotrif (Afitinib), I heard the side effect is stronger than 1st generation. Besides exon21 mutations develops drug resistant sooner. My non-professional logic is stronger medicine may cause resistance to happen sooner, also once 2nd generation becomes ineffective, she has only 3rd generation left to use. She cannot handle chemo due to her age and conditions. My logic is to use medicine in the sequence from 1st, to 2nd, and 3rd generation. My mom’s family has longevity so I’m trying to help her to have a good and long fight on the cancer. But we also want to keep her quality of life.
Please help! Your input is greatly appreciated! God Bless!

August 30, 2017 at 5:51 pm  #1291340    
JimC Forum Moderator
JimC Forum Moderator

Hi blesswen,

I am so sorry to hear of your mother’s diagnosis. I can understand the choice not to have surgery or chemotherapy. The differences between Iressa and Tarceva are not that significant. The standard Tarceva dosage of 150 mg/day is somewhat stronger than the standard Iressa dosage, so some oncologists use a lower Tarceva dose, and patients who are sensitive to the drug can do well all the way down to 25 mg/day. The side effects are really quite similar between these two, and there are cases of interstitial lung disease and liver issues with Tarceva as well as Iressa. Afatinib tends to be a bit tougher to tolerate than the other two.

As far as moving from first to second to third generation EGFR inhibitors, it’s not as straightforward as one might think. Afatinib does not tend to be very effective after Tarceva or Iressa, so most patients who progress on those agents move on to third generation inhibitors.

There are also newer EGFR inhibitors that are being tested as first-line EGFR therapy; you can watch a discussion about one of them here.

It’s also not clear that a “stronger” EGFR inhibitor causes resistance sooner, and we don’t understand why some patients get a more durable response than others.

Good luck with the therapy you choose.

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 31, 2017 at 10:38 pm  #1291347    

blesswen

Dear Jim,

For some reason my mom’s doctor never proposed Tarceva. Yesterday the doctor prescribed Afatinib 30mg for my mom after we expressed our concerns about her frail conditions. I read about dose reduction needed for 40% of the patients on Afatinib. Is Afatinib 30mg much more bearable than 40mg? I have a friend (53 years old) whose liver enzyme shoot up after taking Afatinib 30mg. Typically elderly are more sensitive to drug effects and my mom is 87. My mother-in-law also got NSCLC, her 2nd chemo pill caused her to die from Septicemia so I’m really worried about my mom.

For L858R, is there a significant difference between Tarceva and Afatinib on PFS and OS?

My sister and I still prefer Tarceva based on our own research. One good thing is the different dosages available for adjustments and it seems to be an effective drug for L858R. Am I correct? If there’s no significant difference on PFS and OS, we’d prefer to get a second opinion and try to get Tarceva for mom so she won’t get whacked down quickly like my mother-in-law.

Regarding dosage, do people always go from highest dosage first and then lower? Do people taking 25mg or 30mg start from high first? I wonder what approach/dosage we should use for my mom. Somehow here in Taiwan the doctors always prescribe 150mg with less frequency as the way to reduce dosage. I feel by doing so, the fluctuation in the body is big – the first day is high (strong side effects, too) and the last day is low. I prefer, like 25mg/day so the medicine in the blood is more stable.

So sorry, I have so many questions. I appreciate your time and help!

Have a wonderful long weekend and God Bless!

September 1, 2017 at 11:04 am  #1291350    
catdander forum moderator
catdander forum moderator

In the following link you’ll find a discussion about the lux lung 7 trial that compared afatinib to irissa. It was found that afatinib had a better progression free survival rate (PFS) than did irissa. (But the real endpoint will be OS which hasn’t been measured yet.) It wasn’t a hugely significant difference. This leads to another question, is afatinib more effective than tarceva. Dr. West stated, “The very poor data we have to compare them is mixed but has at least suggested to me that Tarceva is perhaps marginally superior to Iressa, so I wouldn’t presume that Tarceva will fall closer in efficacy results to Iressa than Gilotrif. That said, Gilotrif is the only EGFR TKI we have that has shown superior efficacy directly compared to another, an important finding that I believe should factor into our decisions about which EGFR TKI to recommend to our EGFR mutation-positive patients.”
The Lux Lung 7 trial did show efficacy was as good for L858R as for exon 19, answering the question left in previous trials as to whether afatinib was as good for exon 19 as for exon 21 with L858R.

http://cancergrace.org/lung/2016/01/12/ll7-esmo-asia15/

The following is a link to a previous discussion on afatinib including how the trial design compares a lot of unequal parts to make it’s efficacy points.

http://cancergrace.org/lung/2014/06/18/gilotrif-os-benefit/

http://cancergrace.org/lung/2017/08/16/asco-2017-lung-cancer-dacomitinib-beats-iressa-as-first-line-treatment-for-egfr-mutation-positive-nsclc/

In the above link 3 oncs discuss a new drug not on the market yet. But they discuss the learning curve that has formed about managing toxicity if the patient and nurse are motivated. So it’s worth a listen.

Con’t.

September 1, 2017 at 11:15 am  #1291351    
catdander forum moderator
catdander forum moderator

I wish there was an answer but as you’re probably learning there aren’t near enough answers but options are so much greater today in both treatment and side effect management than just a few years ago or months even. Someone living with your mom who can stay on top of how she’s doing working with a nurse (easy to find) at the cancer center can help tremendously in managing side effects. It’s possible yous mom will breeze through afatinib. but it’s not possible to compare one person’s experience with another. People differ greatly in how well a drug is tolerated.

Please keep us posted and don’t hesitate to continue to ask questions.
All best,
Janine

September 1, 2017 at 12:31 pm  #1291353    

blesswen

Dear Janine,

Regarding dosage, do people always go from highest dosage first and then lower?

What’s the better way to adjust dosage? Just to take a lower dosage pill daily or space out the time to take medication – like taking every other day. I feel by spacing out, the fluctuation in the body is bigger – the first day is high (strong side effects, too) and the last day the drug effect is low. I feel it’s probably better to keep the medication in the blood stable.

Thank you so much for your help! God Bless!

Jeannie

September 2, 2017 at 9:06 am  #1291361    
JimC Forum Moderator
JimC Forum Moderator

Hi Jeannie,

Most often, patients begin at the standard dosage, mostly because clinical trials have shown that dose to be tolerated by most patients, and that the specified dosage has shown efficacy. Once that “maximum tolerated dose” has been established in early-phase clinical trials, lower dosages don’t tend to be tested.

But oncology is as much an art as a science, so there is certainly room for individualization. If the oncologist feels that a lower dose would minimize side effects for a particular patient, then that dose can be recommended. Unless the cancer appears to be progressing at a very fast rate, it is reasonable to start low and raise the dose if the drug is well-tolerated but the response is less than anticipated, although that can be a tough determination, since each patient can achieve a different level of response, and with Stage IV disease, even stability without tumor shrinkage is a good result.

As far as side effects if a larger dose is taken less frequently, that doesn’t tend to be well studied either, but a number of patients who have been given “pulsed” Tarceva (e.g., 600 mg every four days) do not seem to experience more significant side effects than those who receive 150 mg per day.

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 11:17 am  #1291363    

blesswen

Dear Jim,

Thank you so much for your response and info!

Exon 21 is more likely to develop drug resistance sooner. In Taiwan standard dosages are more available so the doctors typically ask patients to take every other day or so as a way to reduce the dosage. Would that cause patient to develop drug resistance sooner as what was noted by Dr. Sequist in the paragraph below?

“Sometimes patients will modify oral regimens on their own, thinking that they’ve figured out a well tolerated schedule. Perhaps they take drug for 5 days and then take 2 days off. This is particularly the case when they’ve been on treatment for several months. After a period of time, the safety profile can change. “You might not get the acute symptoms like rash or diarrhea, but you’ll see nail changes or stomatitis,” Dr Sequist said. The clinician needs to ask at each visit whether the patient is taking pills every day. “Although ‘stop dose and hold’ is a great strategy for dealing with acute toxicities, a chronic pattern of holding doses is not generally a good long-term approach,” she explained. Frequent cycling on and off medication can result in more rapid development of resistance. It is better to dose reduce to a more tolerable dose than to take the medication intermittently.”

Thank you and have a great long weekend!

Jeannie

September 2, 2017 at 1:47 pm  #1291369    
catdander forum moderator
catdander forum moderator

Jeannie,

I found Dr. Sequist’s comment here, https://jnccn360.org/nsclc/jnccn-spotlights/afatinib/ which was quoted from another source.

30mg is a quarter less than the tested dose of 40mg so she already will start lower than usual. In the article link to in this post Dr. Sequist discusses what she normally does when a person has difficulty after beginning afatinib, “If patients are having trouble with moderate symptoms when they first start afatinib, “I tell them to hold the dose for about 5 to 7 days. This is for those situations where the side effect is substantial enough to be uncomfortable but not serious enough to signal a medical issue.” In some circumstances, it will be clear that dose reduction is required. Often, though, after about a week off medicine, Dr Sequist explains that patients can re-start without the same level of side effects occurring again. “The same dose is often better tolerated the second time around,” she commented.”

Your mom or a caregiver can discuss these issues with her oncologist with the aid of the appropriate resources and I’m sure can come up with a plan that is both practical for the Taiwanese health system and adhere to the practices of clinical researchers. A large amount of the research into EGFR TKIs has been done in Asia so this info won’t be unusual to her oncologist.

In any event no one knows how your mom will react to the drug. Given the event she has moderate side effects she can cycle through the above mentioned week off then back onto the same dose to see if she responds more favorably the second go around.

Please keep us posted.
All best,
Janine

September 2, 2017 at 1:59 pm  #1291370    
catdander forum moderator
catdander forum moderator

I want to mention that it’s not unusual for medical oncologists in the US to use advise given to them from resources provided by patients. A major reason for Dr. West starting Grace was to give patients and caregivers resources for treatment planning. Medical oncologists who treat many types of cancer aren’t able to keep up with the fast evolving cancer care of the many types of cancer they treat and sometimes miss the most up to date info (even with the sophisticated matrix of info they have at their fingertips). So the info you’ve just provided could help your mom and the oncologist who wants to treat her as well as possible I’m sure. So don’t feel defeated without first having that conversation. You’re likely to be relieved.

September 2, 2017 at 10:04 pm  #1291378    

blesswen

Dear Janine,

Thank you so much for taking the time to look up the source and respond to me! I am so grateful to have found this website. It’s truly a Godsend for the patients and caregivers. It has not been easy for me to do the research since English is not my first language and the research papers are hard to understand. Thank you, Jim, and Dr. West for being here to support and answer questions. I will provide the info for my sister to discuss with the doctor. I will keep you posted.

God Bless!

Jeannie

September 4, 2017 at 12:32 pm  #1291400    

blesswen

We have been focusing on choosing the TKI medication for my mom. Yesterday my sister went to see a Radiologist who told her that my mom may only need radiation treatment. He suggested for IIIb, she may need 30 min/day, 5 days/wk, and 6 weeks of treatment. If the tumor disappears, she may not need to take medication. I think my sister was hoping that my mom can do without taking medication.

I’m very concerned. I don’t think the radiation can cure the cancer. I haven’t read about people getting radiation only for advanced stage adenocarcinoma. I have a few questions:

1) My mom had only CT scan but no PET scan. Can CT scan detect small mets in the body? She could be stage IV….

2) I thought radiation is a local treatment rather than the system treatment. If there are cancer cells in the body, even if the tumor (CT scan reads 4.5cm; bone scan reads 6 cm) disappears, she still needs to take medication. Am I correct?

3) Delaying TKI medication for 6 weeks seems to be very risky to me. My question is, for her age and frail condition, is it safe for her to handle the toxicity to get radiation and TKI at the same time?

4) Is radiation treatment really beneficial? I read about radiation side effects which can be serious.

I’m prone to just start with TKI alone. I’m so undecisive and stressed out. So is my sister. Help!!

Thank you very much in advance for your advice!

Jeannie

September 4, 2017 at 2:40 pm  #1291401    
catdander forum moderator
catdander forum moderator

Jeannie,

There’s some basics I think will help you grasp what’s going on.

You’re right that a pet scan is used to detect “hot spots” that may point to progression. It’s standard practice to have a pet during staging of nsclc diagnosis.
“A prominent use for the PET scan (or combination PET/CT) is in achieving accurate staging of cancer.” http://cancergrace.org/cancer-101/2010/09/14/cancer-101-faq-primer-on-pet-scans/

If your mom is stage III then it’s possible that radiation can cure her of the cancer with no other treatment. Radiation is a local treatment and used like surgery for those who surgery isn’t an option. My husband had radiation because his tumor wasn’t accessible and it cured him. He was initially diagnosed stage III and had curative radiation and chemo. However combining systemic therapy with radiation is very difficult on the body and probably wouldn’t be an option for your mom.

On the other hand if there is progression, the cancer has left the area through the blood or lymph system the cancer isn’t considered curable and is stage IV. In stage IV systemic therapy is used to keep the cancer at bay for as long as possible.

Systemic treatment like chemo and targeted therapies are not curative on there own. Local treatment like surgery and radiation can be curative on there own. Chest radiation is usually pretty easy to take when it doesn’t affect the esophagus. When it does (and the radiation onc can tell you if it might or if it really won’t be an issue) it can lead to problems with swallowing but it’s usually pretty manageable especially when the focus is cure. There are steps to take and be prepared for in the event esophagitis is an issue.

The following link is to an introduction to lung cancer that should help. http://cancergrace.org/lung/2010/04/05/an-introduction-to-lung-cancer/

I hope this is helpful.
All best,
Janine

September 4, 2017 at 3:21 pm  #1291403    

blesswen

Dear Janine,

Thank you so much for the information. It’s really helpful! It makes me more relieved.

Jeannie

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