Dr. West,
I'm looking for some other options after Tarceva is determined to not be working, or additions to my current Tarceva regime.
I was dx in Oct 2012 with a large adenocarcinoma in my left lung (6cm x 5cm x 12cm). It was removed with my left lung. I did a 4 round cycle of chemo with cisplatin and permetrexed. I seemed to be doing well with n sign of progression until October 2014. CT showed 2cm tumor in between my 2nd and 3rd ribs (check cavity) on the left side. I sent the biopsy to Foundation and discovered, that I have two rare mutations that were not identified 2 years ago, exon 18 mutations E709K and G719A. I started on Tarceva in November but have had very little response, no shrinkage, maybe some minor progression. My next scan is in May and I am looking for other options. It seems that Tarceva is not as effective on my mutations as the exon 19 and 20 mutation. What do you recommend? Do you know of any trials? I was not PD1 positive. My Dr. suggested adding Avastin as an option to the Tarceva to potentially get some shrinkage.
Are there any therapies you know of that work better with my mutations. I'm a 49 year old female, who never smoked.
Thanks,
RR
Reply # - April 26, 2015, 08:18 AM
Hi RR,
Hi RR,
We'll have Dr. West comment on the exon 18 mutation. I don't think people with exon 18 mutation have been a part of the 3rd generation tki studies since unfortunately tarceva/iressa haven't shown enough efficacy to create "acquired resistance" in that group. Efficacy in the 3rd gen has been greatest in people who acquire the T790 mutation while on tarceva, the mutation is believed to be acquired while on the tki like tarceva thus causing acquired resistance.
At least one of the immunotherapy drugs being studied have stopped the trial in those with squamous nsclc and those with non-squamous because of early determination that it is effective for both. It's expected that it will be FDA approved for non-squamous soon. More on this can be found on the home page of our site and includes this post,
http://cancergrace.org/cancer-treatments/2015/04/21/it_forum_pal_luke_w…
All best,
Janine
Reply # - April 26, 2015, 09:32 AM
The rare mutations beyond the
The rare mutations beyond the exon 19 deletion and L858R substitution on exon 21 don't tend to respond as well to EGFR TKIs like Tarceva (erlotinib), Iressa (gefitinib), or Gilotrif (afatinib), and unfortunately there's no real evidence of any specific treatment being particularly effective for them. There are hundreds of trials for patients who have received remote prior chemo and more recent Tarceva for recurrent NSCLC, but there's no way to recommend any particular one.
As Janine mentioned, at least one immunotherapy, Opdivo (nivolumab), has become available for some patients with chemotherapy-pretreated advanced squamous NSCLC and is likely to become available imminently for advanced non-squamous NSCLC as well. It's possible your insurer will cover it based just on the press release announcing that the trial in non-squamous NSCLC was also positive for a survival benefit for Opdivo, which predicts for a likely approval of Opdivo in that setting in short order.
Otherwise, it's worth bearing in mind that you haven't shown progression while on a platinum-Alimta (pemetrexed) combination -- you had a long interval after being treated, and it's possible it did an excellent job postponing recurrence and that trying something like carboplatin/pemetrexed with or without Avastin (bevacizumab) would be helpful. I have a patient in whom I just started carbo/Alimta for recurrent disease years after she was treated with post-operative cisplatin/Alimta (and then went a long while without recurrence), and she's having a terrific response. Alternatively, Taxotere (docetaxel) is FDA-approved and associated with a survival benefit, and Cyramza (ramucirumab) is approved to slightly improve outcomes with Taxotere.
I think any of these options would be more appealing than trying to add modifiers for Tarceva. Given that these mutations are not consistently responsive, I fear that's just a rabbit hole to chase down.
Good luck.
-Dr. West
Reply # - April 26, 2015, 09:33 AM
Here's a post I wrote on
Here's a post I wrote on recent developments with the immunotherapies for lung cancer:
http://cancergrace.org/lung/2015/04/19/the-immunotherapy-cola-wars/
Reply # - April 27, 2015, 08:47 AM
Hi RR,
Hi RR,
I would just add that although EGFR TKIs such as Tarceva don't tend to be effective with this particular mutation (as Dr. West pointed out), Tarceva can have limited efficacy even for mutation-negative patients. In your case you've been taking it since November and seem to be mostly stable (depending on how "minor" your progression has been). Stable is a good result for second and later line treatment, and Dr. West has often pointed out that when progression is minor, it may be better to stick with "bad brakes vs. no brakes" since you don't know how effective your next treatment choice may be. There are of course a limited number of treatment options (though the list is growing all the time), so you like to get the maximum benefit from each before moving on.
Good luck with your next scan.
JimC
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