Hello Dr West/other helpful oncologists
Thankyou for your time.
This is a invaluable resource.
My mother in law was diagnosed with Stage IV NSCLC in July 2011. Bilateral disease, pleural effusion and pericardial effusion. No other distant disease.
She received 5 rounds of carboplatin/vinorelbine/bevacizumab and was then switched to erlotinib 150mg/D for positive EGFR mutation status in about November 2011. She has remained on this although reduced to 100mg/D in about November 2012, due to intolerable side effects.
Her chest disease has been stable, and she has maintained a good quality of life.
Her most recent CT in late January showed some slow progression of LLL lesions (satellite lesions, the original large 9cm RUL mass has remained stable post initial shrinkage) .
In late February she began to exhibit disordered language production and underwent a craniotomy yesterday for a solitary 3X4X4.5cm L parietal lobe lesion. She seems to have recovered well, neurologically intact with no obvious deficits.
Her oncologist has said that he plans to switch her to afatinib once she is home again.
Please share your thoughts regarding this management strategy.
I also have some specific questions:
1. Is it worth doing any further mutation testing on the tissue from the presumed metastatic lesion?
2. Should she be given pemetrexed (she has never had this agent before) now or later or not at all?
3. If her disease becomes stable again on the afatinib, what would the strategy be when that stops working in the future.
4. what is the most appropriate timing to start new/trial therapies eg. PBMS-936558 anti-PD-1 antibodies, now, or when response to afatinib is also waning.
thanks again for your time.
Sincerely
Daniel Banyasz
Reply # - March 26, 2013, 06:24 AM
Reply To: Treatment strategy after progression on erlotinib,
Hello Daniel,
A few thoughts on your questions:
(1) Although many of the mutations such as EGFR are mutually exclusive with other mutations, it may be helpful to test the tissue to see if there is evidence of resistant mutations such as T790M. Knowledge of such a mutation might help tailor further treatment directed at a specific resistant mutation.
(2)-(3) There are three drugs FDA approved for general use in second- and later-line treatment, Tarceva, Pemetrexed (Alimta) and Docetaxel (Taxotere). Either Alimta or Taxotere would be reasonable, well-tested choices for subsequent treatment, either before or after trial drugs. If you haven't already read it, Dr. West has a good post on choosing second-line treatment: http://cancergrace.org/lung/2008/01/24/selecting-2nd-line-nsclc-rx/ (For what it's worth, my wife was EGFR positive and got good response from both Alimta and Tarceva).
(4) Dr. Weiss discussed when to choose trials here: http://cancergrace.org/lung/topic/clinical-trials/page/2/#post-10761
Good luck with whichever treatment is chosen.
JimC
Forum moderator
Reply # - March 26, 2013, 09:04 PM
Reply To: Treatment strategy after progression on erlotinib,
Unfortunately, you have asked very large questions that don't have clear answers at all, beyond what Jim has offered. There's almost certainly a value to trying Alima (pemetrexed) at some point, whether now or later, and many experts favor Alimta or a platinum/Alimta combination as the first chemo-based approach for the setting of acquired resistance to an EGFR inhibitor (unless a repeat biopsy shows small cell lung cancer, which is one of the only immediately practical outcomes that could be found at a time of re-biopsy).
Because there are no right answers here, I would suggest that you look through the recent lung cancer posts or use the search function to find discussions of these topics, such as "re-biopsy" and "acquired resistance", for instance, to see the range of what is being considered. You could ask each of your questions to a panel of 5 experts and get 5 different answers, and all based on judgment but no good evidence yet. I'd have to suggest that you search for discussion of the topics you're asking about and see what various people are saying. I can't give you answers here without implying that there are actual answers that are evidence-based.
Good luck.
-Dr. West
Reply # - March 26, 2013, 09:27 PM
Reply To: Treatment strategy after progression on erlotinib,
Thanks Dr West for your response, and I do understand that there is no good evidence base for answering my questions.
I was in particular interested in your expert opinion, as an oncologist with an interest in lung cancer.
Perhaps if you feel that you can give your expert opinion, as opposed to a evidence based answer, you could address the question of the merit of switching to a 2nd generation EGFR TKI such as afatinib, in the setting of seeming acquired resitance to erlotinib.
thanks
Daniel Banyasz
Reply # - March 26, 2013, 10:01 PM
Reply To: Treatment strategy after progression on erlotinib,
My personal view is that I haven't been very impressed with afatinib to this point, so I would generally favor moving on to standard chemotherapy in someone who hasn't already been on chemotherapy before. It's not that I'd never consider afatinib, but I tend to relegate it to a later line of treatment in someone who has been off of another EGFR inhibitor for a while -- a setting in which we might see a few months of a transient response. But I'd say that it's more likely that a good chemo regimen will lead to superior results in a chemo-naive patient with convincing, clinically significant progression on an EGFR TKI like Tarceva (erlotinib).
-Dr. West