Split: Neoadjuvant TKI for Rare EGFR: p.E709_T710>D - 1274241

Hi Carrie,

I hope it's OK that I split your subject off from it's original thread. It can get confusing for those responding and less available to those looking for info on neoadjuvant treatments for curative use of TKIs.

Your questions are reasonable (except we couldn't say what one should or shouldn't do) though I'm afraid there isn't enough data to suggest tarceva over conventional chemo in this setting. There's very early work on the subject such as the trial you're thinking about joining.

There are a couple of considerations here. 1. What we know about tarceva is almost all in the advanced nsclc setting and not in a neoadjuvant setting. 2. (there are many ways in which to treat stage III nsclc with lots of opinions and individual extenuating circumstances.) Neoadjuvant is in general a fairly rare treatment choice that is being more closely tested in trials. It is a pretty difficult road with surgery soon after and recovery can be difficult.

One of the abstracts presented this week at ASCO is of a small trial in China where around 30 people were treated with a similar though not those with an exon 20. It appears that those in this trial did as well as those who were treated with conventional chemo.
http://meetinglibrary.asco.org/content/169524-176

In your thought process it's worth considering that tarceva has a much less toxic side effect profile than a chemo doublet. If you don't respond to tarceva will chemo still be an option? Entering a trial is never all about altruism but some people consider that in the decision making process.

I hope this has been helpful.
All best,
Janine

Carrie,

I must confess that I'm really not at all enthusiastic about the role of Tarceva (erllotinib) as a neoadjuvant therapy in this setting. First, it doesn't have a clear role even for patients with an established activating mutation (exon 19 deletion or L858R substitution on exon 21) -- the textbook answer is to not pursue that route, since it's untested and may or may not help.

But in someone with a rare EGFR mutation for which the value of Tarceva is completely questionable, I couldn't be less tempted to follow that path. Chemotherapy is about 1000-fold better established, and I would strongly favor conventional chemo over an alternative that I consider to be a complete unknown and very possibly an inferior choice.

Good luck.
-Dr. West

Tarceva did not halt the growth of my mother-in-law's stage IV NSCLC and the side effects were bigger than we expected.
Hope that helps.

Hi Carrie,

Each of the oncologists listed as investigators in this trial are contributors to the GRACE site, and I'm certain Dr. West is familiar with this study. As with any study, until at least preliminary results are available, there's really no way to know if the treatment plan outlined in the trial will prove effective. At this point, it's an idea of unproven value until tested. As an example, when Tarceva was tested as adjuvant treatment for patients with activating EGFR mutations, a patient group in whom it was expected to show good efficacy, the trial results were negative - patients who received standard adjuvant chemotherapy actually did better.

I think one argument in favor of standard neoadjuvant or adjuvant chemo is that you only get one shot at it. It's not like systemic therapy for stage IV disease, where if one line of therapy doesn't work, you try another. To me that's a strong incentive to use an established treatment plan.

JimC
Forum moderator