1st Line Treatment – MEDI4736 + tremelimumab or Chemo or Others??

Portal Forums Lung/Thoracic Cancer NSCLC Stage IV NSCLC 1st Line Treatment – MEDI4736 + tremelimumab or Chemo or Others??

This topic contains 23 replies, has 4 voices, and was last updated by JimC Forum Moderator JimC Forum Moderator 3 weeks, 2 days ago.

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August 19, 2016 at 10:47 pm  #1288362    

mikelauwy

Hi All

This is my first post here as my mother just got diagnosed with stage IV NSCLC adenocarcinoma in Aug. 60yo, never smoked. EGFR/ALK/ROS1 mutations -ve. She has been coughing since Mid Feb and the symptom had gone worse in recent weeks, including more frequent and difficult cough. PET scan suggest the cancer has metastasized to adrenal gland, neck lymph node on the right and also a bit to the back bone.

We are situated in Hong Kong and through government clinic we have the chance to participate in a clinical trial of using MEDI4736 + tremelimumab as 1st line treatment. The selection process will take 3 weeks probably and with 50% of the chance, candidate could be put in control group that only standard chemo treatment will be given. We have consulted a second opinion in the private sector and got a recommendation to proceed with standard chemo (Carboplatin + Pemetrexed) instead to avoid worsening of tumor and symptoms.

I am more inclined to take the traditional approach first but would like to obtain opinion on this case. In particular:

1. Will a 3-week wait worsen the situation of the tumor? In worse case, it may be a 3-week delay but still going back to chemo treatment if we fall into the control group.
2. Do you think it’s worth to secure a chance in testing the new drugs? Is there any clear advantage in using the new drugs as a 1st line treatment (in view of no PD-L1 testing first performed)?
3. Is standard chemo still a first choice as 1st line treatment in this situation? If chemo is desired, I have heard of adding bevacizumab to the chemo combination would be better but my doctor at private sector is inclined not to add it at first stage. Any opinion on this?

Many thanks for all the comments in advance and my prayers to all of you on the same journey as my family.

August 20, 2016 at 8:42 am  #1288365    
JimC Forum Moderator
JimC Forum Moderator

Hi Mike,

Welcome to GRACE. I’m sorry to hear of your mother’s diagnosis and her worsening symptoms. Although we can’t make a specific recommendation for her treatment choice, I can review some of the factors to consider.

Immunotherapies have gained quite a bit of press lately because some patients have had very good, long-lasting responses, without significant or unmanageable side effects. As Dr. Creelan has written:

To address question of anti-CTLA-4 plus either PD-1 vs. anti-PD-L1:

I believe most would agree that this combination concept is more potent. My understanding is that there are several advantages to the combination: for example, based on scant information so far, the responses seem to be independent of PD-L1 status. There also seems to be a higher proportion of responders as well, although still not as high as we want, which is 100%. At the same time, the combinations do seem to have more autoimmune side-effects as well: GI, skin, endocrine, for example. These are usually quite manageable with courses of steroids or hormone supplementation. Nonetheless, in contrast to chemo where almost everyone has some cumulative toxicity, most patients cruise along with few problems. At the end of the day, most patients are wiling to accept a higher risk of these auto-immune side effects, if it means NOT talking about recurrent lung cancer.
http://cancergrace.org/topic/medi4736/page/3/#post-1265367

On the other hand, many patients do not get that kind of significant, durable response. Perhaps most importantly for your mother’s situation, it can take several weeks for lung cancer to show a response to immunotherapy. If her symptoms are getting worse, that may continue while waiting for immunotherapy to provide a response.

When no driver mutation has been identified, standard chemotherapy remains the first choice treatment, and with adenocarcinoma carbo/Alimta is a very popular regimen, in part due to its favorable side effect profile.

[continued]


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 20, 2016 at 8:52 am  #1288366    
JimC Forum Moderator
JimC Forum Moderator

[continued from previous post]

Symptom improvement may be seen after one or two infusions, and it’s typical to re-scan after two cycles to determine efficacy. If continued progression is seen with that regimen, a decision may be made to change therapies. A patient might need to wait a bit longer to give immunotherapy a chance to reveal its true effectiveness.

The value of adding bevacizumab to a standard chemo doublet is not clear. Its approval was based on a single trial that showed an incremental benefit, but other trials have not clearly demonstrated that benefit.

I hope that whichever treatment choice is made provides timely relief of symptoms and long-lasting response.

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 20, 2016 at 11:50 pm  #1288383    

mikelauwy

Hi Jim

Many thanks for your input. With inadequate results from the new drugs, I believe we will take the traditional chemo approach first for faster lessening of symptoms and hope there would be other opportunities just in case 2nd line treatment is required.

Thanks for your help and comment

Mike

August 22, 2016 at 7:47 pm  #1288404    
catdander forum moderator
catdander forum moderator

MIke,

I’m glad we could help answer your questions however I must respond to your last statement. Unfortunately cancer is most often not curable when there are metastases outside the lung where the primary tumor is found; however it is treatable and even maintained for many years. I say all this to say that if your mom’s cancer has spread she will most likely need 2nd line treatment at some point.

“Most likely” is a term I use a lot because up until until about 10 years ago standard chemotherapies were the only systemic anti cancer treatments available for nsclc. Now there are targeted therapies that some people have taken successfully for 5 years and more without progression of the cancer. Treatments for nsclc are growing quicker now than anytime in the past but for now those who are responding remarkably well to treatments are too few and the reasons for that are not well understood.

Another growing topic of study is the idea of oligo-metastases, if a person has just 1 or 2 metastases there are instances where they have been treated with curitive intent and have not had the cancer come back. Though this too remains too few and still understudied and not understood.

Lastly the people who have cancers that aren’t curable are living longer and better than anytime in the past due to better palliative care (care one gets for no other reason than to feel better). Good studies have shown people who get good palliative care live significantly longer and better than those who don’t.

Really lastly ;) personally my husband had what is considered a very difficult to treat squam nsclc which had grown into the chest wall and caused lots of damage, it was treated with rad/chemo (standard fare). Not only that but it was believed that he had 2 mets that remained undiagnosed. Today he’s not had treatment for 3 1/2 years and is NED.

There’s always hope.
Janine

August 25, 2016 at 9:45 am  #1288434    

mikelauwy

Hi Janine

Many thanks for your sharing as well. In view of the recent advancement in medicine and technology, I agree there is always hope when there is a desire to live, or at least achieve a better quality of life with uncurable cancer. My mother has been the most positive among the family ever since the diagnosis, even though she understands much of the medical advancements in the past 10 years could not help her. I believe a positive attitude still helps in getting along with the cancer.

She has started the first dose chemo treatment on this Monday, and from today she started to have greater fatigue, constipation and also pain in part of the ribs while coughing. Understand mostly they are side effects but the bone pain may signify worsening of disease, I wonder if it is too early to say chemo is effective in reliving the cancer or not.

Knowing it’s difficult, but I still hope the symptoms and side effects won’t hit her positive attitude.

Best Regards
Mike

August 25, 2016 at 5:17 pm  #1288438    
catdander forum moderator
catdander forum moderator

Hi Mike,
It’s not expected to see results after just one treatment. However side effects are pretty common. Fortunately they can usually be managed. If your mom is having uncontrolled pain and diarrhea or other symptoms her treatment team should be alerted at once so they a plan can be made and put to action.

I hope she is feeling better soon.

Janine

January 25, 2017 at 11:41 pm  #1289901    

mikelauwy

Hi All

It’s been some time since my last post. Would like to provide some update and get some insight on proper next step.

My mother had finished 4 cycles of carbo + alimta with minimal side effects. Her PET scan afterwards shown improvement in the lung and bone mets, and also her CEI has dropped from over 4000 to around 600. Symptom-wise she had also improved greatly that her cough had stopped completely. The doctors at our government sector followed their standard procedure to stop the carbo and remain alimta as maintenance therapy

This is where things go the other way round. Her coughing resumed before the second alimta maintenance treatment and CEI had rose to over 700. Situation did not improve after the 3rd alimta only dose and a PET scan was arranged and it turns out the main tumor and also the bone/adrenal gland mets had all worsen. Doctor suggested alimta is of no use any more and suggested to start keytruda at 2mg/KG/3weeks as a next step (without PDL1 testing).

We consulted our doctors at private sector for second opinion and he believed we stopped carbo which shown to provide benefits too early. Nevertheless, he suggested to go on docextal + carbo or immunotherapy. Knowing that we are subsidized to use the expensive keytruda at public sector, he agreed we should try it first but showed concerns on my mon’s status getting worse if keytruda is not effective and doctors at gov sector being too confident with immunotherapy. At his recommendation, we arranged PDL1 testing with the sample tissue, obtained in Aug 2016 at a swollen lymph node that was used for diagnostic of the lung cancer and also the EGFR/ALK -ve status.

My mom did her first Keytruda injection last Fri, and had (from our view) no immunotherapy related side effects up to now. She is still coughing and occasionally having small pain at hip bones suspected to relate to the bone mets. And we are still waiting for the PDL1 testing result.

(to be continued)

January 25, 2017 at 11:42 pm  #1289902    

mikelauwy

(continued)

1. Do you think such PDL1 testing can be used as an accurate indicator on the effectiveness of Keytruda? How should we and the doctors treat the PDL1 testing results?

2. I understand the chances of keytruda working is quite low given my mom’s non-smoker status. Before another PET scan can be arranged, how the doctors and/or we should pay attention to find out if keytruda is working or not. What is the proper time to stop if there is no improvement?

3. It seems that we are left with the older types of chemo to try if keytruda is not working. Since carbo was the agent that provided the greatest benefit in the past, would it still be beneficial to go back to alimta/carbo or another carbo combination at that time?

Many thanks for all advice in advance

Mike

January 26, 2017 at 6:07 am  #1289903    
JimC Forum Moderator
JimC Forum Moderator

Hi Mike,

I’m sorry to hear of your mom’s progression. Although as you say the percentage of patients who get a very good response to immunotherapy is low, we will hope that your mom is in that group of responders.

There are two ways to judge response to treatment — follow-up scans and clinical observation of improving symptoms. But as we discussed previously, it can take a bit longer for immunotherapy to show results, as opposed to standard chemotherapy, perhaps a couple of months. In that time, it is possible that her symptoms may worsen somewhat, making it more difficult to determine response. Of course, if she starts feeling better that is an excellent sign that therapy is working. I don’t think that the PD-L1 test results will be as important as her apparent improvement, on scans and clinically.

If her cancer progressed while on Alimta maintenance, there’s not much reason to return to it. If a change is deemed necessary, most oncologists considering standard chemotherapy would opt for a single-agent such as docetaxel (Taxotere) rather than a platinum-based combination regimen. Extended use of platinum agents tends to have cumulative effects, including a decrease in bone marrow function, which can decrease blood counts and make further chemo difficult to administer. That’s not to say that it can’t be done, especially if she was continuing to respond well after her third and fourth cycles of carbo/Alimta.

Good luck with Keytruda.

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

January 26, 2017 at 6:45 am  #1289904    

mikelauwy

Hi Jim

Many thanks for your comment. Just to add that we just got the PDL1 testing result that was from the right SCF node biopsy, and unfortunately it was determined as <1%. So there is a great chance keytruda would not work. Given this, do you think we should stop keytruda immediately and go for another chemo, or keep on the course for say 6 weeks and wait for worsening or improving symptoms/scans.

Apart from the cough, she is still performing well physically and could still have the energy to join social activities throughout various treatment, but now she feels devastated with the testing results and seems hope is lost. I would like to try to cheer her up while planning for the worst.

Best Regards
Mike

January 26, 2017 at 8:33 am  #1289905    
catdander forum moderator
catdander forum moderator

I’m so sorry your mom didn’t test better. Normally oncologists prefer to not drop a treatment before real proof of failure is proven through scans and clinical signs. There’s still a chance it will have some benefit from the immunotherapy. As Jim said time will tell.

Even though she isn’t EGFR positive tarceva has proven some benefit in later line treatment.

From what I understand it’s all but impossible to forget and the truth about the cancer you have and when the mind does forget for a moment it comes back with a vengeance. So being happy may have a different meaning for your mom and “finding moments” of contentedness is a perfectly appropriate counter to “having a good time”. From my personal experience as a loved one and through my years on Grace it seems the best way to raise spirits is spending time with friends and loved ones, doing things she enjoys, that bring her joy. Some people travel, go to the mountains or the beach, visit the people she hasn’t seen in too long. I imagine the act of you trying fits into the category of things she loves.

Keep us posted and I’m hoping the hear good things.
All best,
Janine

January 30, 2017 at 6:48 am  #1289929    

scohn

Hi Mike.

Just a note of support with more hopes and prayers that your Mom has good results on the immunotherapy.

I don’t know if you talked about this with the doctors, but you might want to discuss with the doctors the possibility of doing a liquid (blood) biopsy to try and detect the actual mutations driving the cancer. While the tests do have less sensitivity than physical biopsies, they can often help determine the presence of rarer types of mutations, and sometimes give the doctors more information that might help them determine the best later lines of treatment, or which clinical trials might be most appropriate.

Thoughts and prayers are with your family for successful outcomes, and treatments that last a very long time!


Wife, lifelong non-smoker, dx 4/24/15 adeno NSCLC stage IV, poorly diff. 2 bone mets, 1 lymph node. HER2 Exon 20 mutation. 6x Carbo/Alimta – >50% reduction in primary tumor, lymph nodes, & bone. Alimta maint. not effective, tumor growth, new liver mets. 11/15 – Opdivo; Not effective-add’l growth. 4/16 – clinical trial drug, large reduction of tumor and mets. 11/16-main tumor growth, liver mets stable. 2/17-All Stable. 8/17- Add’l growth-off trial, 9/17 start Gemzar

April 18, 2017 at 7:39 am  #1290597    

mikelauwy

Hi All

It’s been a while and would like to share the latest status and get some support. My mom has gone through 3 rounds of keytruda and even though the symptoms (mainly cough) got mildly worse, CEA has risen from around 1200 before immunotherapy to near 4000, and PET-CT scan has shown progression and increased metabolism at multiple sites. Our oncologist determined keytruda is of no use and suggested to switch back to chemo with taxol/carbo as the combination.

She had her first dose 3 weeks ago and has been difficult in tolerating it, much more than when she had alimta/carbo. She had numb fingers and feet, and hair loss which had greatly affected her as a person having great concerns of her own look. More importantly, her blood test last week had shown very low white blood cell counts which may affect her next infusion this week. Since symptoms use she does not have much improvement yet, she is worrying such the effort and hardship she endured would prove no use.

Also since the middle of immunotherapy, she starts to suddenly had ‘twisting’ pain at the right waist only during cough. The pain does not appear otherwise and would lessen to nil even at cough after a few days. But after a few days again, the pain would come back. The oncologist only provide pain relieving medications (panadol) without further looking into the cost. We wonder if it was due to the bone metastases or if there are some kind of lung damaged by heavy coughing as every time it arouse during cough. She had developed such symptom again this morning and it was the first time she can’t withstand and took medication for relieving pain.

To be continued

April 18, 2017 at 7:40 am  #1290598    

mikelauwy

Continued

It seems that we are out of options. On the rebiopsy, oncologist only suggests to do it for egfr patients (to test if there is t790m mutation). And seems there are no more clinical trial for patients after keytruda is used (despite clinical trials are already difficult to find in my place). I now could just look for methods to relief her pain and methods (eg diet) that could help to increase her white blood cell counts in order to continue the treatment.

Best regards
Mike

April 18, 2017 at 4:08 pm  #1290599    

scohn

Hi Mike.

Just want you to know we’re out here think about you and your Mom and hoping the taxol provides some help. I don’t know if it is an option for you, but when my wife’s white blood cells plummeted on chemo, they gave her shots of Xgeva that definitely helped to boost the WBC.

Sending internet hugs of hope and healing to you and your Mom!


Wife, lifelong non-smoker, dx 4/24/15 adeno NSCLC stage IV, poorly diff. 2 bone mets, 1 lymph node. HER2 Exon 20 mutation. 6x Carbo/Alimta – >50% reduction in primary tumor, lymph nodes, & bone. Alimta maint. not effective, tumor growth, new liver mets. 11/15 – Opdivo; Not effective-add’l growth. 4/16 – clinical trial drug, large reduction of tumor and mets. 11/16-main tumor growth, liver mets stable. 2/17-All Stable. 8/17- Add’l growth-off trial, 9/17 start Gemzar

April 18, 2017 at 5:06 pm  #1290600    
JimC Forum Moderator
JimC Forum Moderator

Hi Mike,

I’m sorry to hear that the Keytruda was not effective for your mom, and that she’s struggling so much with side effects from carbo/taxol. Taxol can be challenging for many patients, especially as far as neuropathy, hair loss and low blood counts. One option which might be available in place of Taxol is Abraxane, which is essentially the same drug formulated in a different manner, resulting in fewer side effects. When my late wife’s oncologist recommended Taxol, we substituted Abraxane, which caused no significant side effects. You’d need to find out whether your insurance would cover it, as it is expensive, but since she is struggling with Taxol, there is a good argument that Abraxane is medically necessary. My wife’s insurance covered it even before it was FDA-approved.

As far as the pain when she coughs, it would be difficult to guess what might be causing that. Perhaps further workup by your mom’s medical team might unearth the cause; otherwise, if her treatment is altered that might resolve the problems.

Also, it might be worth asking your mom’s oncologist about dropping the carboplatin. Many oncologists do not return to the platinum doublet after first-line therapy, preferring single-agent regimens instead due to the cumulative effects of continued platinum therapy, such as reduced bone-marrow function which in turn can affect blood counts.

I hope that your mom can find relief from her symptoms, and that she gets a good response from treatment.

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

July 23, 2017 at 11:09 pm  #1291119    

mikelauwy

Hi All

A brief update on my mom’s progress and to seek some further opinion.

She had 5 rounds of Paclitaxel and carbo up to now (with dosage dropped since the 2nd round due to low white blood cell count) and the CEA did drop from ~4000 to ~2400 at the 3rd infusion. She has been able to cope with the side effects, and the PET scan done after the 4th round also shown satisfactory improvement that near all of the tumors had shrunk in size and activity. However, the CEA value also stabilize and re-increased to ~2900 before the 5th round. She will have her 6th round next week and after that, our primary doctor suggest to pause as he afraid her body cannot cope with the accumulated toxicity.

We have also consulted 2nd opinion again through private sector and was suggested to test for a few more actionable mutations (BRAF, RET, MET exon 14 skipping and 1 another) but got a negative result for all of them.

Here is a summary of the treatment so far.

CEA ~4500 to begin with
Alimta + Carbo ( 4 rounds, CEA dropped to ~700)
Alimta maintenance (3 rounds, CEA increased to ~1200)
Keytruda (3 rounds, CEA increased to ~4000)
Paclitaxel + Carbo (5 rounds, CEA dropped to ~2400 before going up to ~2900 again)

Her physical status is still good at the moment, with less cough and a better PET scan result compared to the time ending keytruda treatment. However, it seems the situation could go worse soon given the rising CEA values and we are running out of options.

I have a few queries.

1. Is it still worth to seek trying another immunotherapy (though both our doctors at government and private sector did not suggest it as an option). It seems only PDL-1 inhibitors are available in my area but not CTLA-4

2. Is there still other chemotherapy that she can/should try or even re-use? Her doctors refuse to suggest until they think she really needs it. And I could not find much information online regarding 3rd or 4th line chemo treatment.

Best regards
Mike

July 24, 2017 at 12:12 pm  #1291121    
catdander forum moderator
catdander forum moderator

Hi Mike,

It’s good to hear your mom is doing alright. I hope she’s able to recoup a bit before beginning another treatment.

Unfortunately most oncologists including lung cancer specialists aren’t likely to want to try a second immune checkpoint inhibitor. At least not outside a trial. At this time there are no CTLA-4 drugs proven to extend life for those with lung cancer. There are some trials that are testing combinations of PD-1/L1 inhibitors with CTLA-4 inhibitors. The toxicity profile seems to be rough for some.

You’re not likely to find much about specific treatments for later lines of treatment though you can look to suggested 2nd line treatments for later line treatments. The list below can all used in later line treatment. Taxol, taxotere, abraxane and navelbine can all cause peripheral neuropathy and since your mom has had taxol it would probably be best to stay away from those that cause neuropathy from now on. This neuropathy can cause significant problems with continued use after neuropathy has begun.

Paclitaxel (Taxol)
Albumin-bound paclitaxel (nab-paclitaxel, Abraxane)
Docetaxel (Taxotere)
Gemcitabine (Gemzar)
Vinorelbine (Navelbine)
Irinotecan (Camptosar)
Pemetrexed (Alimta)

It’s not been the custom to move back to a drug once stopped. Historically oncs have used up a drug before moving on. These days drugs like alimta have shown long term benefits without many or all side effects that outwardly cause one to feel bad but have ultimately been taken off of it because of high creatinine blood test. Once blood creatinine is back to acceptable limits alimta has been used again. If your mom didn’t progress (shown on CT) on alimta moving back to it would be an option.

Cont.

July 24, 2017 at 12:18 pm  #1291122    
catdander forum moderator
catdander forum moderator

Genetic testing for actionable mutations in clinical trials is an excellent idea. I’ll leave you with a link to a discussion on second opinions that includes a little info on clinical trials. (if you want more info on trials we have a series that’s very informative.) There’s a lot going on in this field right now. http://cancergrace.org/cancer-101/2011/11/13/an-insiders-guide-to-the-second-opinion/

I don’t know if this has been discussed on here before but wanted to warn against making treatment decision based on CEA levels. They can be erratic in lung cancer and don’t necessarily point to progression. Perhaps if you mom showed progression every time the levels rise and shrinkage every time CEA lowered you could be cautiously sure of the numbers meaning. But in deciding to change treatments especially at this point you want a really good reason like clear progression by CT or side effects that don’t justify treatment. You can also use scanning and cancer symptoms as a gauge to start up treatment so your mom has a chance to break from treatment to heal from toxicities of treatment.

Please keep us posted and I hope you mom does well for a long time.

All best,
Janine

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