Acquired Resistance - 1274223

stoner50
Posts:2

My wife was diagnosed with stage 4 NSCLC at age 61 in january 2013, with bone/ 15 brain mets at dx, EGFR +, exon 19. She did well on Tarceva, with gamma knife to brain and some spot bone met XRT. In January 2016, PET revealed progression just in left hilum; EBUS + adenoca there with +T790M. No evidence of active disease in brain or bone.
As a result, prescribed Tagresso 80 mg in 1/2016. PET at 2 months later showed mild PET response. PET in May 2016 showed substantial progression in same area of lung and hilum (but not in prior sites of disease in bone or elsewhere). The progressing areas are close together and will be treated with cyberknife in 2 weeks. Radiologist optimistic that cyberknife will be successful.
I would appreciate any thoughts regarding the pros and cons of treatment going forward. Return to Tarceva, as it appears to have been effective except in one small area of the lung; try afatinib, with or without cetuximab, as she is exon 19; continue Targresso; go to standard chemo - cisplatin or carbo/alimta? also have read of ongoing trials of an Astellas Pharma drug ASP8273, but have not been able to determine the results of these studies.
Any information/thoughts would be most appreciated.

Forums

JimC
Posts: 2753

Hello,

I don't think there's any right answer here, but there certainly is a trend toward local treatment of an "oligometastasis" when all other sites have been resolved or are stable. In that situation, the targeted therapy (in this case Tarceva) is continued, in the hopes that it will continue to be effective in all other areas. By doing so, you are able to get the maximum benefit from each therapy.

If progression continues, there isn't much evidence of response to afatinib alone, and while the combination with cetuximab can be effective, the skin toxicities and other side effects can be very difficult. Other options will probably need to be evaluated at that time, which I hope is a long way down the road.

JimC
Forum moderator

stoner50
Posts: 2

thanks Jim for your prompt response.
my thoughts agree with yours, but am still thinking that continuing Tagrisso may make sense, although i would also prefer to hold that until later.
would greatly appreciate
Dr. Creelan's thoughts on this dilemma.
all the best

catdander
Posts:

I hope you don't mind, I've split your topic away from the original topic which is to introduce the FDA approval of Tagrisso. This way more people in a similar circumstance can access this discussion.

I'll invite Dr. Creelan to respond but if he's at ASCO (American Society of Clinical Oncology annual conference) he may be unable to respond and quite busy when he returns to his practice.

All Best,
Janine

JimC
Posts: 2753

At a GRACE reception at ASCO over the weekend, I did ask one of Dr. West's colleagues in the oncology community about your situation, and he agreed that there is no right answer, but that since the change to Tagrisso has been made, it's perfectly reasonable to stay with it. He felt that if you placed your situation in the hands of a group of oncologists, you would get many different responses, including not switching from Tarceva to Tagrisso at the first sign of progression. It's not a set of circumstances in which there is clear clinical evidence as to the best course of action, but in theory, if those are the only spots which are displaying the T790M mutation, the hope would be that radiation would eliminate those and that Tagrisso would prevent the development of other areas of resistance.

JimC
Forum moderator