blood based cancer drug test - 1265189

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

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

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.

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

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.