blood based cancer drug test

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This topic contains 6 replies, has 3 voices, and was last updated by  texandave 3 years, 3 months ago.

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July 29, 2014 at 4:52 pm  #1265189    

ssflxl

Dear All

Here’s an article that makes me wonder why Astra wants to have this companion test done. Wouldn’t they have a larger market if they just say that AZD 9291 works for most people who progress on 1st generation TKI since their Phase II study did show that about 20% of those who were neg for T790M mutation did respond. Now they limit their meds to only those who test pos for T790M with their companion test. I would think they can get FDA approval even if they didn’t have this test.

http://news.yahoo.com/astrazeneca-taps-roche-qiagen-blood-based-cancer-drug-061925035–finance.html

ssflxl


Non smoker Asian F, St 4 NSCLC – 11/2010, 6 cm LUL mass, met to paraspinal muscle, +EGFR at Exon 21 L858R. Tarceva in 11/2010, rad to lung mass and met. 5/2012 – PET showed inc SUV in primary cancer, new 1.6 cm lesion in left thoracic inlet causing Horner’s syndrome. Cyberknife to lesion – 5/2012. Restarted Tarceva 75mg/day -5/12, reduced to 50mg. 8/12 – PET- thoracic inlet lesion gone. 11/12 PET – inc SUV in primary tumor, ant mammary node, some SUV uptake in a fibrotic area in apex. Biopsy of this showed fibrosis and scant atypical cell. Cyberknife to mammary node, continue Tarceva. PET-10/13 – incr SUV to 14 in left primary tumor and new 1cm nodule in LUL, no new symptom. 12/13 – biopsy of LUL- same Exon 21, L858R – ?no T790M. on Tarceva 75/50. 1/14 PET – not much change. 2/14 – arm pain, cough, sob. CT – inc tumor to 5.5×5.9 with LUL collapse. 2/14 – Carbo/Pem x6. 4/14 PET – dec SUV but new bony lesions. PET in 6/14 – stable. start Pem every 3 wks in 7/14, Pamidronate every 6 wk.

July 29, 2014 at 7:35 pm  #1265190    
Dr West
Dr West

It isn’t clear that AZD9291 works any better for T790M negative patients than just retreating with Tarceva (erlotinib) or some other EGFR inhibitor — the responses were much shorter than in T790M positive patients, and they were mostly seen in people who had been off of an EFGR TKI for a long while.

The FDA is becoming far more motivated about approving targeted therapies only, or at least very preferentially, in highly targeted populations. Moreover, there is plenty of money to be made in offering a test used by a larger population, even if the drug is only given to a narrower population. It may well be a better strategy to identify a population with a 60-70% response rate to a drug you sell by using a test you also sell than to have much less enthusiastic use of that drug because its activity is clearly much less in a less selected group.

-Dr. West

July 29, 2014 at 7:42 pm  #1265191    

ssflxl

Dr. West

Thanks for your thoughts. Things are changing rapidly. I am glad that at least they don’t ask for biopsy since they already know that doing so would really limit the use of their drug. I read somewhere that Astra and Clovis both plan to file for FDA approval next year – probably late next year, so maybe they will have the companion test ready by then??!!

ssflxl


Non smoker Asian F, St 4 NSCLC – 11/2010, 6 cm LUL mass, met to paraspinal muscle, +EGFR at Exon 21 L858R. Tarceva in 11/2010, rad to lung mass and met. 5/2012 – PET showed inc SUV in primary cancer, new 1.6 cm lesion in left thoracic inlet causing Horner’s syndrome. Cyberknife to lesion – 5/2012. Restarted Tarceva 75mg/day -5/12, reduced to 50mg. 8/12 – PET- thoracic inlet lesion gone. 11/12 PET – inc SUV in primary tumor, ant mammary node, some SUV uptake in a fibrotic area in apex. Biopsy of this showed fibrosis and scant atypical cell. Cyberknife to mammary node, continue Tarceva. PET-10/13 – incr SUV to 14 in left primary tumor and new 1cm nodule in LUL, no new symptom. 12/13 – biopsy of LUL- same Exon 21, L858R – ?no T790M. on Tarceva 75/50. 1/14 PET – not much change. 2/14 – arm pain, cough, sob. CT – inc tumor to 5.5×5.9 with LUL collapse. 2/14 – Carbo/Pem x6. 4/14 PET – dec SUV but new bony lesions. PET in 6/14 – stable. start Pem every 3 wks in 7/14, Pamidronate every 6 wk.

July 30, 2014 at 11:27 am  #1265192    
Dr West
Dr West

I don’t know details, but I hope to learn more in the coming months. My center is just opening a trial with CO1686 now.

-Dr. West

July 31, 2014 at 8:55 pm  #1265206    

texandave

Dr. West, do you know if there is any research involving the development of the t790m mutation (percentages, diagnoses, exons) and the duration of EGFR Inhibitor treatment prior to looking for that and other mutations? I would wonder if a patient would test “positive” for t790m or any other mutation if he/she took Tarceva for four months versus four years. Can you test positive for more than one mutation? Then what is the thinking with AZD9291 and co-1686 versus Tarceva, Iressa and Gilotrif? Do these “next drugs” hold the cancer at bay, and does the identificaton of t790m mutation mean that much other than determining eligibility? What I read is for AZD9291 if you are 23% likely to respond, but to go down the immunotherapy road you face less than 20%, EGFR+ or otherwise. This is what I would inquire about in a monotherapy drug trial with an initial prior treatment washout with risk of flare.

July 31, 2014 at 11:10 pm  #1265210    
Dr West
Dr West

There is no data, no evidence to suggest that people are more or less likely to have a T790M mutation as a function of the duration of their response. There is a bit of information published by Dr. Geoff Oxnard, who is a participant on our faculty, that people with a T790M mutation often have progression limited to the chest, slower progression, and a better performance status than acquired resistance by a different mechanism, which tends to be more fulminant. However, these are just concepts in broad strokes, and there hasn’t been much other work to draw any real conclusions about clinical patterns with T790M.

There will be studies comparing AZD9291 or CO1686 to other EGFR inhibitors, such as the first generation ones we’ve been using, as first line therapy for EGFR mutation-positive patients, but at this time there is no evidence to say that the newer drugs are better for first line therapy, and I would not presume that to be the case. Remember that even if the newer drugs lead to a slightly longer progression-free survival, they would probably need to be better than first line Tarceva or Iressa, followed by AZD9291 or CO1686, which could be a very effective sequential combination that likely wouldn’t be effective with one of the newer drugs followed by one of the older ones.

And you just can’t compare response rates that are almost identical in two different small trials with different populations. None of these numbers should be interpreted as a solid, reliable answer about what to expect when you’re talking about a trial or two with a few dozen patients. If you overinterpret small samples, you could visit my home in Seattle in July and presume it’s always 85% and sunny…but that’s not a reliable sampling of reality. I can assure you that none of the numbers you’re reading from the early phase II trials is a reliable number.

-Dr. West

August 1, 2014 at 3:19 pm  #1265217    

texandave

Dr. West, I made a mistake on my post regarding one of the early numbers coming out regarding the AZD9291 therapy. I did not clarify that the 23% was the figure quoted of people who were responders at this very early research stage who tested negative for t790m who were being shown to respond to this point, versus 64% response who tested positive for the t790m mutation. I agree that the studies are promising but still quite young. I apologize for not catching my mistake because it can be confusing to anyone who read my prior post. Likewise, we know that hopefully the “immunotherapy” statistics will improve with time and good scientific research. Hopefully, financial logistics will get some consideration from someone who envisions therapy “combinations” better than the present.

Likewise, I agree with you on a majority of what you have to say about research drug studies and issues that patients must consider when making uncertain decisions in their next steps of treatment. The majority. My brother lived near Redmond for five years when with Microsoft. I hope that you enjoy your sun, and the coffee and chocolate that non-sun makes us crave a little more.

Your availability at this site cannot be overstated as a physician who works in 2014 with patient and research clinical challenges. Your credentials are known to be outstanding. My oncologist, Dr. Larry Frase, speaks highly of you. Thank you for what you offer to patients out of your very stretched time.

No response is necessary to this post. Thank you again.

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