Tagrisso first line and then Tarceva therapy - 1288422

Hi NT,

The jury is still out and we just don't know if one is better than another much less why. Still the standard of care, the treatment we know to be beneficial is 1st gen for 1st line and 3 gen if acquired resistance with a t790m mutation occurs.

There are new and ongoing studies testing the efficacy of tagrisso in the front line setting. The first 2 in the links below are studying the efficacy of tagrisso given to those who have been found to have an EGFR mutation with T790M at diagnosis. The reasoning behind these first 2 is pretty simple; egfr positive with an acquired t790m has been shown to respond to tagrisso so it stands to reason that someone with both egfr mutation and t790m at diagnosis may respond well to tagrisso, hence the trial.

The 3rd link is a trial is comparing efficacy of tagrisso to tarceva (or iressa) in front line treatment with only a diagnosis of egfr positive mutation with or without the t790m mutation. You don't know until you try and some people without t790m mutation definitely respond to tagrisso (though to a lesser extent than those with t790m).

https://clinicaltrials.gov/ct2/show/NCT02841579?term=Tagrisso&intr=1st+…
https://clinicaltrials.gov/ct2/show/NCT02769286?term=Tagrisso&intr=1st+…
https://clinicaltrials.gov/ct2/show/NCT02296125?term=Tagrisso&intr=1st+…

Dr. West shares his thoughts on moving straight to 3 gen tki as first line treatment, http://cancergrace.org/lung/2015/11/13/lcam_2015_west_third_generation_…
He suggests here that 1st and 2nd gen tki s may not be very beneficial given after 3rd gen tagrisso. All this will be sorted out when the data are in.

I know this isn't an answer but still I hope it's helpful,
Janine

Through Emory University Dr. S.S. Ramalingam is the lead principal investigator for the FLAURA study. Luckily (mostly through the hard work done by Dr. West) Dr. Ramalingam is on our faculty and sent in this comment on your question,

“Tagrisso is being studied in the first line therapy setting to see if shutting down the T790 escape (resistance) mechanism pro-actively will improve the outcome for patients. The approach has shown promising early results and are now being studied in a large clinical trial. This trial compares tagrisso directly with tarceva or iressa. We are still learning about what mechanisms of resistance are observed when patients are treated with tagrisso in the first line setting. It is possible that for a subset of these patients, using iressa or tarceva after they have received tagrisso might be beneficial, but it is too early at this time to make firm statements on this issue.The presently available data are based on laboratory experiments and have not been confirmed in patients”