pemetrexed vs pemetrexed/erlotinib in EGFR acquired resistance

Portal Forums Cancer Treatments / Symptom Management EGFR Inhibitors pemetrexed vs pemetrexed/erlotinib in EGFR acquired resistance

This topic contains 4 replies, has 2 voices, and was last updated by catdander forum moderator catdander forum moderator 1 month, 1 week ago.

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March 14, 2017 at 12:25 pm  #1290362    

jjkk

Is there any benefit to sequential use of pemetrexed with erlotinib vs pemetrexed alone in EGFR mutant cancer thats progressing with acquired resistance to erlotinib?

March 15, 2017 at 8:31 am  #1290368    
catdander forum moderator
catdander forum moderator

Hi jjkk,

I’m sorry it’s taken so much time to get to your question. I think you mean concurrent use of pem and erlotinib (taken together). The general thinking is to use TKIs for as long as they are keeping the cancer in check. This includes a TKI that has begun to allow slow progression but the cancer symptoms are manageable and you are being seen and scan regularly so changes can be made when needed. For some practice can work as long or longer than the initial response. Think of the analogy that the TKI is bad breaks; well bad breaks are better than no breaks and you want the cancer in check for as long as possible. Dr. Weiss talks about what to do when TKIs start to be less effective, http://cancergrace.org/lung/2014/10/08/ar_forum_after_1st_line_targeted_therapy/

There has been a trial that showed avastin combined with erlotinib provided better progression free survival though the toxicities occurred in most patients and almost 40% had to dropped out of the trial due to toxicities. Dr. Pennell talks about this and other chemo options here, http://cancergrace.org/lung/2014/10/17/ar_forum_using_non_off_targeted_therapies/

This link provides the video library of an acquired resistance conference that still applies with the possible exception of 3 gen drugs like tagrisso. http://cancergrace.org/lung/acquired-resistance-patient-forum-2014-videos/

Most lung experts aren’t combining (concurrent) TKIs with chemo but use them separately (sequentially).

I hope this helps.
All best,
Janine


My husband, 8/09 53 @ dx stage III squam nsclc R. pancoast tumor
Destruction of 3 ribs, touching brachial plexus.
6/09-8/09 2 core and 1 VATS undx biopsies. Open thoracotomy for 1 positive biopsy (unresectable)
9/09 Chemo/rads curative intent
11/09 MRI by pancoast specialist surgeon spine met found undiagnosed Rad to spine, Chemo continued thru 6 cycles
Tarceva maintenance 2/10
11/10 3cm tumor L lung, undx core bx w/collapsed lung. Gemzar, 12/10 through 7/12
NED 3/12, stop tx 7/12. Remains NED as of 9/16
Unanswerable question. Was it ever metastatic?

March 15, 2017 at 8:41 am  #1290369    
catdander forum moderator
catdander forum moderator

I meant to lead with this post to answer your question.

From Dr. Riley on the IMPRESS trial that studied EGFR TKI 1st gen with chemo, “Now, I say that not to frighten people, but to point out that, often, in patients with EGFR mutant lung cancer, there is still some benefit for continuation of EGFR TKI, and there may be a role for continuing with chemotherapy. Importantly, this has been studied in a randomized fashion, so patients with EGFR mutant lung cancer with resistance to first-generation EGFR tyrosine-kinase inhibitors, were randomized to chemotherapy with an EGFR tyrosine-kinase inhibitor, and there wasn’t a difference in the outcome. So, it wasn’t clear in an overall patient population that it mattered if you continued. So, this data really indicates that it’s okay not to continue EGFR tyrosine-kinase inhibitors. I think the one area that I might disagree is maybe in the initial switch from an EGFR tyrosine-kinase inhibitor to the chemotherapy — it would be reasonable to overlap those so that you’re getting the benefits of the chemotherapy and we’re seeing shrinkage of the chemotherapy before you pull back on the EGFR tyrosine-kinase inhibitor.” http://cancergrace.org/lung/tag/impress-trial/


My husband, 8/09 53 @ dx stage III squam nsclc R. pancoast tumor
Destruction of 3 ribs, touching brachial plexus.
6/09-8/09 2 core and 1 VATS undx biopsies. Open thoracotomy for 1 positive biopsy (unresectable)
9/09 Chemo/rads curative intent
11/09 MRI by pancoast specialist surgeon spine met found undiagnosed Rad to spine, Chemo continued thru 6 cycles
Tarceva maintenance 2/10
11/10 3cm tumor L lung, undx core bx w/collapsed lung. Gemzar, 12/10 through 7/12
NED 3/12, stop tx 7/12. Remains NED as of 9/16
Unanswerable question. Was it ever metastatic?

March 15, 2017 at 1:38 pm  #1290376    

jjkk

Thank you for your response. What I meant specifically is there any benefit of giving pemetrexed every 3 weeks and using erlotonib on days inbetween (days 2-16) as some of the tumor cells are still responsive to TKIs. I read that TKI suppress thymidylate synthase (TS) expression, and low TS expression is predictive factor for pemetrexed efficacy. I read a study showing its effectiveness was better than using pemetrexed alone and just wanted anyones insight/input as to its effectiveness in clinical practice? thanks

March 15, 2017 at 2:42 pm  #1290378    
catdander forum moderator
catdander forum moderator

Thanks for clarifying. Current thought suggests using erlotinib as long as possible on its own before making changes in the systemic treatment. However if there are only a couple of spots of progression local therapy can be used. Dr. Weiss talks about that in the first link in the post above.

Chemo has been paired with TKIs to combine efforts. Much or most of the current thought is alimta and other chemotherapies are best left to be used on their own. Alimta on its own can have excellent durability with few or even no side effects. That way treatment options are used at the slowest rate possible also using less allows for better comfort and quality of life.

Janine


My husband, 8/09 53 @ dx stage III squam nsclc R. pancoast tumor
Destruction of 3 ribs, touching brachial plexus.
6/09-8/09 2 core and 1 VATS undx biopsies. Open thoracotomy for 1 positive biopsy (unresectable)
9/09 Chemo/rads curative intent
11/09 MRI by pancoast specialist surgeon spine met found undiagnosed Rad to spine, Chemo continued thru 6 cycles
Tarceva maintenance 2/10
11/10 3cm tumor L lung, undx core bx w/collapsed lung. Gemzar, 12/10 through 7/12
NED 3/12, stop tx 7/12. Remains NED as of 9/16
Unanswerable question. Was it ever metastatic?

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