PEMBROLIZUMAB AS FIRST LINE FOR ALL LUNG CANCERS

Portal Forums Cancer Treatments / Symptom Management Immune-based Therapy / Vaccines PEMBROLIZUMAB AS FIRST LINE FOR ALL LUNG CANCERS

This topic contains 9 replies, has 4 voices, and was last updated by JimC Forum Moderator JimC Forum Moderator 9 months, 2 weeks ago.

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November 15, 2016 at 7:36 pm  #1289193    

JJoshiMD

JJoshiMD says:

Even though all guideline recommends EGFR and ALK testing at diagnosis in all non-squamous Lung cancers, in the real world of community hospitals, this is seldom done, primarily because Medicare will reimburse hospitals for such testing only if done > 14 days after hospital discharge. This dictum will also apply to PD-L1 testing.

The pembrolizumab study in the NEJM yesterday excluded patients not tested for EGFR and ALK and those who did not get a core biopsy (fine needle aspirates were not permitted). The Medicare rule plus those exclusion criteria will likely greatly reduce the numbers of patients who may benefit from pembrolizumab.

So here is a question for you, Dr. West

An actionable mutation is highly unlikely in smokers and those with squamous histology. Would Pembrolizumab not be appropriate (and will insurances pay for it) for a patient who has a PD-L1 tumor proportional score >50% on FNA but has squamous histology and is a heavy smoker?

Thanks
J Joshi, MD

November 16, 2016 at 6:18 am  #1289195    
JimC Forum Moderator
JimC Forum Moderator

Hi JJoshMD,

Welcome to GRACE. As far as using pembrolizumab first-line, it has been approved for NSCLC, but not in that setting, so individual insurers may not be willing to cover it. In addition, though some patients have good, durable responses, the overall response rate is fairly low. Finally, these immunotherapies often take longer to display their efficacy than standard chemo, a factor that may tip the balance toward chemo in many patients with rapidly progressing disease.

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

November 18, 2016 at 4:08 pm  #1289224    

JJoshiMD

Can you please ask Dr. West to comment. Thanks

November 19, 2016 at 6:53 am  #1289226    
JimC Forum Moderator
JimC Forum Moderator

Earlier this year, Dr. West discussed current trials testing the use of immunotherapy, including pembrolizumab, as first-line treatment for NSCLC, either alone or in combination with chemotherapy: http://cancergrace.org/lung/2016/04/27/west_immunotherapy_first_line_treatment/

Dr. Garon discussed the same issue here: http://cancergrace.org/lung/2016/01/16/gcvl_lu_immunotherapy_first_line_therapy_advanced_nsclc/

I will pass on your request to Dr. West, and if he has anything to add either he or I will post his comments.

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

November 19, 2016 at 1:24 pm  #1289229    
Dr West
Dr West

I believe that in real practice, a patient with high PD-L1 expression will be a candidate for Keytruda (pembrolizumab) whether testing is on a core or on a fine needle aspirate (FNA). However, given the escalating importance of tissue testing, most lung cancer specialists strongly favor seeking a core biopsy anyway. There is just too much of a need for testing for multiple potentially relevant molecular targets to continue to rely on an FNA.

As for the KEYNOTE-024 trial on which the Keytruda approval was based, I believe that the trial only excluded patients with a known EGFR mutation or ALK rearrangement, because these patients are still more likely to benefit from targeted therapy against their particular target than either immunotherapy or chemotherapy (and most experts agree that patients with an EGFR mutation or ALK rearrangement are among those least likely to benefit significantly from immunotherapy).

In practice, I think that a patient will merely need to test positive for high expression of PD-L1, regardless of whether it’s from a core biopsy or cytology, and there won’t be any demand or expectation to show results on EGFR and ALK testing. But it will be appropriate to test patients who have non-squamous NSCLC or a minimal or no smoking hisoty for EGFR, ALK, and probably also ROS1 to check whether a targeted therapy might be the best choice for them. Our current recommendations don’t restrict patients from molecular marker testing based on having a history of smoking, even if that affects the pre-test probability of a test coming back positive.

I hope that helps.
-Dr. West

February 11, 2017 at 7:56 am  #1290042    

joshua

First,I do apologise if I use this forum not in appropriate way and out of place.Unfortunatly,I am not very familiar with the technics and technological advances of our present times.I am 71 years old and should be a sufficiant explanation for my lack of expertise and exprience in using,what to most people seems simple.
This was the introduction,now to the point.
I have written to this forum some months ago and received a prompt and helpful response.My question relates to my wife who has advanced lung cancer Adenocarcinoma NSCLC(.PD-L1 strong positive)
She is on first line Keytruda treatment. At first her scans showed – stable.
She had so far 9 sessions of Ketruda 150 mg. every 3 weeks.
Her last PET-CT showed progression and her tumors in the lungs increased in size and some additional ones showed up also in her lymph . She had pneomatitis prior to having the scan and was treated with a moderate streoid pills. Prural liquid from her lung showed no cancerouse signs.
My wife oncologist (to whom we have great respect and confidence) suggested to go on with Keytruda and added Gemzar 300 mg. every week (my wife takes very badly to chemotherapy) .So far we dont know the results .
The dilema is what ,under these circumstances, would be recommended.
Dr. West has given outstanding response to our problem,for which we are very greatful.
Many thanks in advance for your guidness.
(sorry,my English is far from being perfect)
Joshua

February 11, 2017 at 7:59 am  #1290043    

joshua

FORGOT TO MENTION THAT MY WIFE IS KRAS MUTATION.
Joshua

February 12, 2017 at 9:14 am  #1290045    
JimC Forum Moderator
JimC Forum Moderator

Hi Joshua,

I’m sorry to hear that your wife’s cancer has progressed, and I hope that the addition of Gemzar will bring it back under control.

The field of immunotherapy for lung cancer is still relatively new, with many questions yet to be answered. Some of those questions center on the subject of immunotherapy combinations, either with other immunotherapies or standard chemotherapy. Generally, if immunotherapy fails, oncologists will follow it with standard chemotherapy, but other options are currently being studied. Dr. West has written posts about Immunotherapy Combinations and in a post about first-line use of immunotherapy, he discussed clinical trials combining immunotherapy and standard chemo agents.

We don’t know the results of these studies yet, leaving oncologists to use their best judgment. In your wife’s case, it seems that her oncologist feels that Keytruda may still be having an effect, and that adding Gemzar will improve results. It’s a reasonable approach to a question that doesn’t have a clear-cut answer.

Good luck with the new treatment 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

February 12, 2017 at 9:32 am  #1290046    

joshua

Dear JimC,

Thanks for your prompt reply for which I very greatful.

I would appreciate if you could indicate other combinations for my wifes condition.
Please .can you please send me the link to Dr.West article.

Thanks again.
Joshua

February 12, 2017 at 9:50 am  #1290048    
JimC Forum Moderator
JimC Forum Moderator

Hi Joshua,

Sorry for the confusion. The text that appears in green (“Immunotherapy Combinations” and a few words later “post”) are links which you can click to get to Dr. West’s posts. If the links aren’t working for you, here they are in full:

http://cancergrace.org/lung/2016/04/28/west_immunotherapy_combinations/

http://cancergrace.org/lung/2016/04/27/west_immunotherapy_first_line_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

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