Targeted Therapy Vs. Chemo - 1259161

kwieder
Posts:9

NSCLC Andenocarcenoma

My 65 year-old wife had surgical resection of right lower and middle lobs almost two years ago, followed by adjuvant Cisplatin & Pemetrexed 4x. One year ago scan showed small nodules in left lung. Subsequent scans showed slow but steady growth of nodules. Needle biopsy in June showed return of cancer.

Tissue sample sent to FoundationOne. Genomic Alterations identified;
EGFR H773L, V774M
CDKN2A/B loss
CTNNB1 S33F
MCL1 Amplification

She's become increasingly symptomatic with intermittent cough, shortness of breath, and mild fatigue. Oncologist suggests either a doublet of Carboplatin & Pemetrexed or Tarceva, leaving the decision up to us of which one to start with - knowing that the one we choose will sooner or later be followed by the other.

I have two questions:

1. What criteria should one use when making this type of decision? She's a former smoker, but did well with the adjuvant treatment which I presume is similar to the proposed chemo.

2. I've recently read about Cytometric Testing which would necessitate another biopsy for live cells but apparently promises a 90% chance of identifying the drugs that would actually work. Instead of trial and error and perhaps many months of trying drugs that don't work would this be a sensible trade-off?
Many Thanks!
Ken

Forums

catdander
Posts:

Hi Ken,

I'm very sorry your wife's cancer has returned. There is a recent video blog that discusses the situation of treatment planning for exon 20 deletion EGFR which I understand is associated with V774M. http://cancergrace.org/lung/tag/exon-20-2/

These are the results from a search of exon 20. There has been a bit of discussion on the subject. http://cancergrace.org/search-results?q=exon%2020

On the subject of cytometric testing, there's no data to suggest these tests are able to predict what will be most effective though one could easily not try a drug that will work because of false results.

Don't hesitate to ask follow up questions.

All the best,
Janine
forum moderator

Dr West
Posts: 4735

While there is a lot that isn't known in the field of lung cancer, one that I can say is that tests that promise 90% probability of predicting beneficial agents are marketing hype, not actual evidence. I don't ever use these labs, and I know of no experts in lung cancer who know the best evidence and feel there is any clear reason to do so.

With regard to whether to use chemo or Tarceva, it's really just a judgment call, and I don't think it's likely to matter which comes first if you end up doing each in succession.

-Dr. West

carrigallen
Posts: 194

I agree with Janine. Cytometric testing was a popular idea in the late 1990's but has largely fallen out of favor due to its cumbersome process, frequent bacterial contamination, and lengthy time before any results are available. As Dr West has said, how tumors grow in lab mice or Petri dishes often has little to do with how they truly grow in the human body. I say it has largely fallen out of favor in the academic community, but there remain several specialized industry labs that aggressively promote their testing, for a hefty price. I personally don't know of any medical oncologists that advocate or endorse this service.

Aside from EGFR, the genetic alterations you mention do not have any direct 'prime-time' implications for standard treatment, but may be helpful for clinical trial considerations. I think it is best she make an informed decision after carefully reviewing the risks and benefits of tarceva vs chemotherapy. Good luck!

kwieder
Posts: 9

Thank you for your responses! Cytometric testing is definitely out!

As per description of my wife's condition described in first posting on this thread - recurrent NSCLC adenocarcinoma with slow growing (so far) nodules measuring 6-7 mm in left lung (middle and lower lobes of right lung resected two years ago) with some indication of growth in right upper lobe.

Before making the decision as to whether to resume treatment with either chemo doublet (Pemetrexed/Carboplatin) or Tarceva we were made aware of a clinical trial of an immunomodulator drug, Nivolumab with Ipilimumab. She interviewed with intake physician and is an acceptable candidate for the trial, which precludes the treatment with chemo or Tarceva. There is no PD1 positive requirement.

From my own research (including GRACE) I'm seeing reports of positive response rates ranging from 13-25%, with low level of side effects (under 5%?). It would be approx. two months on this trial with infusion every two weeks before we could evaluate if it was working or not. We were told that since she is still in relatively good health, a decision at that time to leave trial and start chemo/Tarceva regime would work as well then as it would now.

I've always been under the impression that joining a clinical trial is done when all other treatments have failed. Is it premature for my wife to enter a trial at this point?

As a side note, the trial physician recommended a brain scan as well as a pet scan whether she joins trial or not. Our oncologist has not mentioned either. Are these scans generally done at this stage?

Thanks again,
Ken

catdander
Posts:

Hi Ken,
I'm glad to know things are moving slow enough to make a well informed decision.

Trials at every stage of lung cancer treatment can be a good move. It depends on the person, their cancer, and the trial. The doctors have said often that discussing treatment options with a researcher at each treatment change stage is the best way to vet your options. So no trials aren't just for last resorts.

This is a link to a blog post on second opinions but it also discusses trial options, http://cancergrace.org/cancer-101/2011/11/13/an-insider%E2%80%99s-guide…

The PD 1 and PD L1 trials are moving forward and remain promising. You may have listened to this but will link just in case, http://cancergrace.org/lung/2013/06/21/mpdl3280a-spigel-asco-2013-nsclc/

I hope this helps,
Janine

Dr West
Posts: 4735

I think the side effect profile of the combination of ipilumumab with nivolumab is quite a bit more challenging than nivolumab alone and far more than 5%.

It is absolutely incorrect that clinical trials are only a last resort. A terribly harmful bit of misinformation that likely dramatically slows the progress on new treatments for lung cancer and others.

Neither a PET scan nor a brain scan are clearly indicated in routine management after initial staging of advanced NSCLC. Though they can both be appropriate in particular situations, they are also over-ordered and not clearly of value in many cases in which they are ordered rather gratuitously.

-Dr. West

kwieder
Posts: 9

Unfortunately, I was mislead by the patient consent form for the nivolumab trial referred to above. Although the consent form we were given clearly states the trial involves both nivolumab and ipilumab, the trial oncologist assures us that my wife can be treated with nivolumab alone! That would change the side effects picture considerably. I apologize for the confusion.

So our decision now is between joining the trial or going ahead with the chemo doublet. If we went chemo now, that apparently takes her out of consideration for nivolumab at least in terms of how the current trial eligibilities are stated.

The GRACE videos where the promise of immunomodulators is discussed is very encouraging and we are teetering on the fence as to which way to go. My wife is in reasonably good health with symptoms that are not at this time that limiting.

Would appreciate any guidance in helping us decide on a strategy.

Thanks again,
Ken

JimC
Posts: 2753

Hi Ken,

One factor that many patients take into account is that the chemo option will be available after the trial but the opposite may not be true, so you have an additional option if you choose the trial.

JimC
Forum moderator

Dr West
Posts: 4735

I agree that one of the key factors I consider is how best to maximize the options available to a person over time. If one option is only available on a limited basis and another is available now or later, I typically favor the option that allows both treatments over time.

Good luck.

-Dr. West