EGFR l858r Stage IV progression after 6 months on Tarceva - 1290867

Hi shopping14,

Welcome to Grace. I'm so sorry you've progressed already on tarceva. I think you have several decent options. A Chemo doublet with or without avastin added remains the standard of care in a scenario you've described. Often alimta (with and without avastin) as maintenance (directly after doublet) or at the time of progression after doublet continues to work for months or in some cases years. It also has an excellent side effect profile, some people even describe no side effects.

Afatinib on the other hand seems to have a bit more difficult side effect profile and without much chance of efficacy after progression on tarceva. Adding cetuximab has shown to have some efficacy though with the possibility of more side effects with its addition may make this combo less attractive. The following link is to a patient group that participated in a trial with this combo. http://cancergrace.org/search-results?q=Afatinib%20%2BCetuximab

Dr. West wrote this blog post on the subject of combining keytruda and chemo.
It speaks specifically about those with PD-L1 expression over 50% so his thoughts about it not being ready for "prime time" would apply to those without PD-L1 expression.
http://cancergrace.org/lung/2017/01/12/imprecision-medicine-why-keytrud…

Trials remain a good choice if your onc thinks there's a good possibility to help but there's no way to know its efficacy profile.

We can't say what you should do but we want you to have the info you need to make the decision that's right for you. Let us know if you have further questions.

All best,
Janine

This quote is from 2011 not long after x geva was approved but it still applies.
"Xgeva has certain clear advantages over zometa. 1st, it is a shot so for patients not receiving IV chemo (for example, a patient on tarceva) using xgeva avoids the need to have an IV inserted. It's also safe with kidney dysfunction, unlike zometa which requires, at the minimum, dose reduction. Finally, the comparison data indicates slightly improved efficacy over zometa. However, the absolute difference in efficacy is small and the absolute difference in price is very large. If I were a patient, this is not a difference that I would be willing to pay for out of pocket." http://cancergrace.org/forums/index.php?topic=9140.0

I hope this was helpful.
Janine

Hi shopping14,

I am sorry to hear of your progression on Tarceva, and I hope that whatever course you decide to take has a renewed activity against the cancer and lasts for a long while.

I just wanted to say a couple of words about Xgeva/Zometa. My wife was on Xgeva during her early carbo/alimta treatments because of her small bone metastases and had no side effects. Unfortunately when she went on the clinical trial, they didn't want her to use Xgeva because they thought the two antibodies might affect one another, so they wanted her to use Zometa instead. My wife has now had two treatments on Zometa, and the side effects seemed a lot like what she experienced with the white blood booster Neulasta she was on with the carbo/alimta. She experienced a general achy-ness and soreness for about a week. Her oncologist suggested that she try taking Claritin with it (as they suggest for Neulasta) to ease the symptoms, so she will try that next time and see how it goes.

Assuming equal effectiveness, my wife definitely preferred the Xgeva and hopes they will let her go back to that at some point.

Also, you say you are not T790M positive. Is the EGFR l858r mutation the original mutation or the one they found that gave resistance to the Tarceva?

All the best for finding a successful and sustaining treatment.

Hi Shopping14.

Thanks for your kind words. The clinical trial drug is an antibody-drug-conjugate (ADC) made by Pfizer, targeting a protein that is found in a number of adenocarcinomas known as PTK7. You can follow much of our trial journey under "clinical trial update" in the Lung cancer patient update section. My wife has been on it for a little over a year now, and, for the most part, the cancer is stable.

We also have another trial in the wings with a drug targeted more directly to the type of mutation my wife has that we would likely go to next if the ADC stops working. The other drug (Ariad Pharmaceutical AP32788) is currently in Phase 1 and they are testing the dosages, so we are hoping that my wife would be stable for at least enough time to make it until the trial is in Phase 2 when they would know the best dosage already. It is a trial you may also want to look at if you find your tumor has re-mutated with an "Exon 20" mutation.

Hope to be hearing great news in the near future about your new treatment and its effectiveness!

Hi Kim,

Scohn has become an expert in working with his wife's onc to find possible trials. I've pasted links to an excellent series of posts about clinical trials I think will be a valuable tool. It may be helpful to get a second opinion from an oncologist who conducts trials, though in general oncologists are most familiar with the trials they participate in. ClinicalTrials.gov has most clinical trials around the world and it has a good search and advanced search.

I think most oncs are hesitant to plan for what comes next because it's impossible to guess what that will be. I think scohn's wife has a specific set of genetic mutation/s for which several drugs are being tested so that gives them the advantage. And unfortunately she's gone through the standard treatments for her histology where you've not exhausted standard of care options. In your position it's important for you and your oncologist to think through options for clinical trials that may be of help while available. Sometimes the thinking is to try a trial drug that is available now but might not be later while standard treatments, in your case chemo will always be available. Too, each trial has its own set of inclusion and exclusion criteria which sometimes has exclusion if you've had some specific treatment (like excluding those who've had immunotherapy for a trial testing a new immunotherapy drug)

Stanford is an excellent place to be seen. Still it's becoming increasingly important to do some of the legwork in finding possible trials because of the vast number of options out there one onc can't keep up with it all. It sounds like you're becoming a part of your own care team and that's impressive. I'm sure Scohn will provide more excellent tips.

http://cancergrace.org/cancer-101/2013/01/06/clin-trials-ramalingam-pt-…
http://cancergrace.org/cancer-101/2013/01/18/how-are-clin-trials-develo…
http://cancergrace.org/cancer-101/2013/01/27/ramalingam-clin-trials-pt-…

All best,
Janine